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Characterization of Newly Isolated Bacteriophages Targeting Carbapenem-Resistant Klebsiella pneumoniae
Bokyung Kim, Shukho Kim, Yoon-Jung Choi, Minsang Shin, Jungmin Kim
J. Microbiol. 2024;62(12):1133-1153.   Published online December 10, 2024
DOI: https://doi.org/10.1007/s12275-024-00180-7
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  • 9 Download
  • 1 Web of Science
  • 2 Crossref
AbstractAbstract PDF
Klebsiella pneumoniae, a Gram-negative opportunistic pathogen, is increasingly resistant to carbapenems in clinical settings. This growing problem necessitates the development of alternative antibiotics, with phage therapy being one promising option. In this study, we investigated novel phages targeting carbapenem-resistant Klebsiella pneumoniae (CRKP) and evaluated their lytic capacity against clinical isolates of CRKP. First, 23 CRKP clinical isolates were characterized using Multi-Locus Sequence Typing (MLST), carbapenemase test, string test, and capsule typing. MLST classified the 23 K. pneumoniae isolates into 10 sequence types (STs), with the capsule types divided into nine known and one unknown type. From sewage samples collected from a tertiary hospital, 38 phages were isolated. Phenotypic and genotypic characterization of these phages was performed using Random Amplification of Polymorphic DNA-PCR (RAPD-PCR), transmission electron microscopy (TEM), and whole genome sequencing (WGS) analysis. Host spectrum analysis revealed that each phage selectively lysed strains sharing the same STs as their hosts, indicating ST-specific activity. These phages were subtyped based on their host spectrum and RAPD-PCR, identifying nine and five groups, respectively. Fourteen phages were selected for further analysis using TEM and WGS, revealing 13 Myoviruses and one Podovirus. Genomic analysis grouped the phages into three clusters: one closely related to Alcyoneusvirus, one to Autographiviridae, and others to Straboviridae. Our results showed that the host spectrum of K. pneumoniae-specific phages corresponds to the STs of the host strain. These 14 novel phages also hold promise as valuable resources for phage therapy against CRKP.

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  • Evaluation of Bacteriophage and Antibiotic Synergy Against Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates
    Bokyung Kim, Shukho Kim, Yoon-Jung Choi, Minsang Shin, Jungmin Kim
    Journal of Bacteriology and Virology.2025; 55(2): 131.     CrossRef
  • Possible regulatory network and associated pathways governing the expression of ADH2 in Saccharomyces cerevisiae
    Pratima Sarkar, Rohan Nath, Prity Adhikary, Arindam Bhattacharjee
    Current Genetics.2025;[Epub]     CrossRef
NEDD4 Regulated Pyroptosis Occurred from Co‑infection between Influenza A Virus and Streptococcus pneumoniae
Jiangzhou You , Linlin Zhou , Xudong San , Hailing Li , Mingyuan Li , Baoning Wang
J. Microbiol. 2023;61(8):777-789.   Published online October 4, 2023
DOI: https://doi.org/10.1007/s12275-023-00076-y
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  • 9 Web of Science
  • 8 Crossref
AbstractAbstract PDF
Co-infection of respiratory tract viruses and bacteria often result in excess mortality, especially pneumonia caused by influenza viruses and Streptococcus pneumoniae. However, the synergistic mechanisms remain poorly understood. Therefore, it is necessary to develop a clearer understanding of the molecular basis of the interaction between influenza virus and Streptococcus pneumonia. Here, we developed the BALB/c mouse model and the A549 cell model to investigate inflammation and pyroptotic cell death during co-infection. Co-infection significantly activated the NLRP3 inflammasome and induced pyroptotic cell death, correlated with excess mortality. The E3 ubiquitin ligase NEDD4 interacted with both NLRP3 and GSDMD, the executor of pyroptosis. NEDD4 negatively regulated NLRP3 while positively regulating GSDMD, thereby modulating inflammation and pyroptotic cell death. Our findings suggest that NEDD4 may play a crucial role in regulating the GSDMD-mediated pyroptosis signaling pathway. Targeting NEDD4 represents a promising approach to mitigate excess mortality during influenza pandemics by suppressing synergistic inflammation during co-infection of influenza A virus and Streptococcus pneumoniae.

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  • GSDMD and GSDME exhibit distinct roles in enteric coronavirus PDCoV-induced pyroptosis and inflammatory responses
    Chenyu Li, Yuting Shi, Chunying Xie, Kaiqi Duan, Tong Ding, Xiangfei Xu, Liurong Fang, Yanrong Zhou, Shaobo Xiao, Tom Gallagher
    Journal of Virology.2025;[Epub]     CrossRef
  • Updated insights into the molecular networks for NLRP3 inflammasome activation
    Seungwha Paik, Jin Kyung Kim, Hyo Jung Shin, Eun-Jin Park, In Soo Kim, Eun-Kyeong Jo
    Cellular & Molecular Immunology.2025; 22(6): 563.     CrossRef
  • Universal and highly sensitive detection of influenza A virus and streptococcus pneumoniae using WGA-modified magnetic SERS nanotags-based lateral flow assay
    Xiaofei Jia, Zhenzhen Liu, Juan Zhou, Chunran Cao, Yunwei Hao, Jin Chen, Han Han, Jing Liang, Zhibin Zhao, Yi Wang, Zhendong Niu, Rui Xiao
    Nanomedicine: Nanotechnology, Biology and Medicine.2025; 69: 102853.     CrossRef
  • Post-influenza bacterial infection: mechanisms of pathogenesis and advances in therapeutic strategies
    Biao Lei, Shun Wang, Linzhong Yu, Qinhai Ma
    Frontiers in Microbiology.2025;[Epub]     CrossRef
  • Pyroptosis in Respiratory Virus Infections: A Narrative Review of Mechanisms, Pathophysiology, and Potential Therapeutic Interventions
    Runqi Lin, Barbara N. Porto
    Microorganisms.2025; 13(9): 2109.     CrossRef
  • Yinqin Qingfei granules alleviate Mycoplasma pneumoniae pneumonia via inhibiting NLRP3 inflammasome-mediated macrophage pyroptosis
    Zhe Song, Chengen Han, Guangzhi Luo, Guangyuan Jia, Xiao Wang, Baoqing Zhang
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Overexpression of DTX1 inhibits D-GalN/TNF-α-induced pyroptosis and inflammation in hepatocytes by regulating NLRP3 ubiquitination
    Mingshui Liu, Jing Gu, Li Chen, Wei Sun, Xiaoping Huang, Jianhe Gan
    Toxicology Research.2024;[Epub]     CrossRef
  • NLRP3 Inflammasomes: Dual Function in Infectious Diseases
    Yanbo Li, Rui Qiang, Zhengmin Cao, Qingjuan Wu, Jiuchong Wang, Wenliang Lyu
    The Journal of Immunology.2024; 213(4): 407.     CrossRef
Varicella‑Zoster Virus ORF39 Transmembrane Protein Suppresses Interferon‑Beta Promoter Activation by Interacting with STING
Gwang Myeong Lee , Shuang Gong , Seong&# , Hyemin Ko , Woo&# , Jihyun Lee , Ok Sarah Shin , Jin&#
J. Microbiol. 2023;61(2):259-270.   Published online February 20, 2023
DOI: https://doi.org/10.1007/s12275-023-00019-7
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  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDF
Varicella-Zoster virus (VZV) causes varicella in primary infection of children and zoster during reactivation in adults. Type I interferon (IFN) signaling suppresses VZV growth, and stimulator of interferon genes (STING) plays an important role in anti-VZV responses by regulating type I IFN signaling. VZV-encoded proteins are shown to inhibit STING-mediated activation of the IFN-β promoter. However, the mechanisms by which VZV regulates STING-mediated signaling pathways are largely unknown. In this study, we demonstrate that the transmembrane protein encoded by VZV open reading frame (ORF) 39 suppresses STING-mediated IFN-β production by interacting with STING. In IFN-β promoter reporter assays, ORF39 protein (ORF39p) inhibited STING-mediated activation of the IFN-β promoter. ORF39p interacted with STING in co-transfection assays, and this interaction was comparable to that of STING dimerization. The cytoplasmic N-terminal 73 amino acids region of ORF39P was not necessary for ORF39 binding and suppression of STING-mediated IFN-β activation. ORF39p also formed a complex containing both STING and TBK1. A recombinant VZV expressing HA-tagged ORF39 was produced using bacmid mutagenesis and showed similar growth to its parent virus. During HA-ORF39 virus infection, the expression level of STING was markedly reduced, and HA-ORF39 interacted with STING. Moreover, HA-ORF39 also colocalized with glycoprotein K (encoded by ORF5) and STING at the Golgi during virus infection. Our results demonstrate that the transmembrane protein ORF39p of VZV plays a role in evading the type I IFN responses by suppressing STINGmediated activation of the IFN-β promoter.

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  • Antiviral effects of heme oxygenase-1 against canine coronavirus and canine influenza virus in vitro
    Jae-Hyeong Kim, Dong-Hwi Kim, Kyu-Beom Lim, Joong-Bok Lee, Seung-Yong Park, Chang-Seon Song, Sang-Won Lee, Dong-Hun Lee, Do-Geun Kim, Hun-Young Yoon, In-Soo Choi
    Journal of Microbiology.2025; 63(5): e2501029.     CrossRef
Biophysical characterization of antibacterial compounds derived from pathogenic fungi Ganoderma boninense
Syahriel Abdullah , Yoon Sin Oh , Min-Kyu Kwak , KhimPhin Chong
J. Microbiol. 2021;59(2):164-174.   Published online December 23, 2020
DOI: https://doi.org/10.1007/s12275-021-0551-8
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  • 11 Web of Science
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AbstractAbstract PDF
There have been relatively few studies which support a link between Ganoderma boninense, a phytopathogenic fungus that is particularly cytotoxic and pathogenic to plant tissues and roots, and antimicrobial compounds. We previously observed that liquid-liquid extraction (LLE) using chloroformmethanol- water at a ratio (1:1:1) was superior at detecting antibacterial activities and significant quantities of antibacterial compounds. Herein, we demonstrate that antibacterial secondary metabolites are produced from G. boninense mycelia. Antibacterial compounds were monitored in concurrent biochemical and biophysical experiments. The combined
methods
included high performance thin-layer chromatography (HPTLC), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR) spectroscopy. The antibacterial compounds derived from mycelia with chloroform-methanol extraction through LLE were isolated via a gradient solvent elution system using HPTLC. The antibacterial activity of the isolated compounds was observed to be the most potent against Staphylococcus aureus ATCC 25923 and multidrug-resistant S. aureus NCTC 11939. GC-MS, HPLC, and FTIR analysis confirmed two antibacterial compounds, which were identified as 4,4,14α-trimethylcholestane (m/z = 414.75; lanostane, C30H54) and ergosta-5,7,22-trien-3β-ol (m/z = 396.65; ergosterol, C28H44O). With the aid of spectroscopic evaluations, ganoboninketal (m/z = 498.66, C30H42O6), which belongs to the 3,4-seco-27-norlanostane triterpene family, was additionally characterized by 2D-NMR analysis. Despite the lack of antibacterial potential exhibited by lanostane; both ergosterol and ganoboninketal displayed significant antibacterial activities against bacterial pathogens. Results provide evidence for the existence of bioactive compounds in the mycelia of the relatively unexplored phytopathogenic G. boninense, together with a robust method for estimating the corresponding potent antibacterial secondary metabolites.

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  • Techno‐Functional Biochemical Analysis and Food Applications of Edible Mushroom Powder
    Subhra De, Prince Chawla, Sanju Bala Dhull, Gulden Goksen, Anarase Dattatray Arjun, Aarti Bains, Nadica Maltar Strmečki
    Journal of Food Biochemistry.2025;[Epub]     CrossRef
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    Shuang Hua, Yanshuang Li, Feng Jin, Meiyao Gan, Xianshun Jiang, Ying Zhang, Bo Zhang, Xiao Li
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    Samantha C. Karunarathna, Nimesha M. Patabendige, Kalani K. Hapuarachchi, Itthayakorn Promputtha
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    Qian-Zhu Li, Chuan Xiong, Wei Chee Wong, Li-Wei Zhou
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  • Plant Defense Inducers and Antioxidant Metabolites Produced During Oil Palm-Ganoderma boninense Interaction In Vitro
    Neda Shokrollahi, Chai-Ling Ho, Nur Ain Izzati Mohd Zainudin, Mohd As’wad Bin Abdul Wahab, Mui-Yun Wong
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    Yow-San Chan, Khim-Phin Chong
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  • Review Update on the Life Cycle, Plant–Microbe Interaction, Genomics, Detection and Control Strategies of the Oil Palm Pathogen Ganoderma boninense
    Izwan Bharudin, Anis Farhan Fatimi Ab Wahab, Muhammad Asyraff Abd Samad, Ng Xin Yie, Madihah Ahmad Zairun, Farah Diba Abu Bakar, Abdul Munir Abdul Murad
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Review
Recent advances in the development of β-lactamase inhibitors
Shivakumar S. Jalde , Hyun Kyung Choi
J. Microbiol. 2020;58(8):633-647.   Published online July 27, 2020
DOI: https://doi.org/10.1007/s12275-020-0285-z
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  • 23 Web of Science
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AbstractAbstract PDF
β-Lactam antibiotics are the most commonly prescribed antibiotics worldwide; however, antimicrobial resistance (AMR) is a global challenge. The β-lactam resistance in Gram-negative bacteria is due to the production of β-lactamases, including extended-spectrum β-lactamases, metallo-β-lactamases, and carbapenem-hydrolyzing class D β-lactamases. To restore the efficacy of BLAs, the most successful strategy is to use them in combination with β-lactamase inhibitors (BLI). Here we review the medically relevant β-lactamase families and penicillins, diazabicyclooctanes, boronic acids, and novel chemical scaffold-based BLIs, in particular approved and under clinical development.

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Journal Article
Streptococcus pneumoniae aminopeptidase N contributes to bacterial virulence and elicits a strong innate immune response through MAPK and PI3K/AKT signaling
Ling Wang , Xuemei Zhang , Guangying Wu , Yuhong Qi , Jinghui Zhang , Jing Yang , Hong Wang , Wenchun Xu
J. Microbiol. 2020;58(4):330-339.   Published online February 27, 2020
DOI: https://doi.org/10.1007/s12275-020-9538-0
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AbstractAbstract PDF
Streptococcus pneumoniae is a Gram-positive pathogen with high morbidity and mortality globally but some of its pathogenesis remains unknown. Previous research has provided evidence that aminopeptidase N (PepN) is most likely a virulence factor of S. pneumoniae. However, its role in S. pneumoniae virulence and its interaction with the host remains to be confirmed. We generated a pepN gene deficient mutant strain and found that its virulence for mice was significantly attenuated as were in vitro adhesion and invasion of host cells. The PepN protein could induce a strong innate immune response in vivo and in vitro and induced secretion of IL-6 and TNF-α by primary peritoneal macrophages via the rapid phosphorylation of MAPK and PI3K/AKT signaling pathways and this was confirmed using specific pathway inhibitors. In conclusion, PepN is a novel virulence factor that is essential for the virulence of S. pneumoniae and induces host innate immunity via MAPK and PI3K/AKT signaling.

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Review
REVIEW] Antibiotic-resistant clones in Gram-negative pathogens: presence of global clones in Korea
Kwan Soo Ko
J. Microbiol. 2019;57(3):195-202.   Published online October 2, 2018
DOI: https://doi.org/10.1007/s12275-019-8491-2
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  • 7 Web of Science
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AbstractAbstract PDF
Antibiotic resistance is a global concern in public health. Antibiotic-resistant clones can spread nationally, internationally, and globally. This review considers representative antibiotic-resistant Gram-negative bacterial clones–CTX-M- 15-producing ST131 in Escherichia coli, extended-spectrum β-lactamase-producing ST11 and KPC-producing ST258 in Klebsiella pneumoniae, IMP-6-producing, carbapenem-resistant ST235 in Pseudomonas aeruginosa, and OXA-23- producing global clone 2 in Acinetobacter baumannii–that have disseminated worldwide, including in Korea. The findings highlight the urgency for systematic monitoring and international cooperation to suppress the emergence and propagation of antibiotic resistance.

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    Journal of Bacteriology and Virology.2021; 51(3): 120.     CrossRef
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    Mohammad Hamidian, Steven J. Nigro
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Journal Articles
Gamma-irradiation of Streptococcus pneumoniae for the use as an immunogenic whole cell vaccine
Min Yong Jwa , Soyoung Jeong , Eun Byeol Ko , A Reum Kim , Hyun Young Kim , Sun Kyung Kim , Ho Seong Seo , Cheol-Heui Yun , Seung Hyun Han
J. Microbiol. 2018;56(8):579-585.   Published online July 25, 2018
DOI: https://doi.org/10.1007/s12275-018-8347-1
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AbstractAbstract PDF
Streptococcus pneumoniae is a major respiratory pathogen that causes millions of deaths worldwide. Although subunit vaccines formulated with the capsular polysaccharides or their protein conjugates are currently-available, low-cost vaccines with wide serotype coverage still remain to be developed, especially for developing countries. Recently, gamma- irradiation has been considered as an effective inactivation
method
to prepare S. pneumoniae vaccine candidate. In this study, we investigated the immunogenicity and protective immunity of gamma-irradiated S. pneumoniae (r-SP), by comparing with heat-inactivated S. pneumoniae (h-SP) and formalin-inactivated S. pneumoniae (f-SP), both of which were made by traditional inactivation methods. Intranasal immunization of C57BL/6 mice with r-SP in combination with cholera toxin as an adjuvant enhanced S. pneumoniaespecific antibodies on the airway mucosal surface and in sera more potently than that with h-SP or f-SP under the same conditions. In addition, sera from mice immunized with r- SP potently induced opsonophagocytic killing activity more effectively than those of h-SP or f-SP, implying that r-SP could induce protective antibodies. Above all, immunization with r-SP effectively protected mice against S. pneumoniae infection. Collectively, these results suggest that gamma- irradiation is an effective method for the development of a killed whole cell pneumococcal vaccine that elicits robust mucosal and systemic immune responses.

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    Michael Pichichero, Richard Malley, Ravinder Kaur, Robert Zagursky, Porter Anderson
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    Augustina K. Arjarquah, Evangeline Obodai, Hannah Ayettey Anie, Michael Aning Osei, John Kofi Odoom, Joseph H. K. Bonney, Eric Behene, Erasmus N. Kotey, James Aboagye, Stephen O. Nyarko, Jeannette Bentum, Clara Yeboah, Selassie Kumordjie, Bright Agbodzi,
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  • Low-Energy Electron Irradiation of Tick-Borne Encephalitis Virus Provides a Protective Inactivated Vaccine
    Julia Finkensieper, Leila Issmail, Jasmin Fertey, Alexandra Rockstroh, Simone Schopf, Bastian Standfest, Martin Thoma, Thomas Grunwald, Sebastian Ulbert
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Non-capsular based immunization approaches to prevent Streptococcus pneumoniae infection
    Pedro H. Silva, Yaneisi Vázquez, Camilo Campusano, Angello Retamal-Díaz, Margarita K. Lay, Christian A. Muñoz, Pablo A. González, Alexis M. Kalergis, Susan M. Bueno
    Frontiers in Cellular and Infection Microbiology.2022;[Epub]     CrossRef
  • A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies
    Shannon C. David, Erin B. Brazel, Eve V. Singleton, Vikrant Minhas, Zoe Laan, Catherine Scougall, Austen Y. Chen, Hui Wang, Chloe J. Gates, Kimberley T. McLean, Jeremy S. Brown, Giuseppe Ercoli, Rachel A. Higgins, Paul V. Licciardi, Kim Mulholland, Justin
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    Huaguo Chen, Cheuk Lun Chow, Denvid Lau
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  • Intranasal Vaccine Delivery Technology for Respiratory Tract Disease Application with a Special Emphasis on Pneumococcal Disease
    William Walkowski, Justin Bassett, Manmeet Bhalla, Blaine A. Pfeifer, Elsa N. Bou Ghanem
    Vaccines.2021; 9(6): 589.     CrossRef
  • Immune Responses to Irradiated Pneumococcal Whole Cell Vaccine
    Eunbyeol Ko, Soyoung Jeong, Min Yong Jwa, A Reum Kim, Ye-Eun Ha, Sun Kyung Kim, Sungho Jeong, Ki Bum Ahn, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
    Vaccines.2021; 9(4): 405.     CrossRef
  • Controlling the Colonization of Clostridium perfringens in Broiler Chickens by an Electron-Beam-Killed Vaccine
    Palmy R. Jesudhasan, Sohini S. Bhatia, Kirthiram K. Sivakumar, Chandni Praveen, Kenneth J. Genovese, Haiqi L. He, Robert Droleskey, Jack L. McReynolds, James A. Byrd, Christina L. Swaggerty, Michael H. Kogut, David J. Nisbet, Suresh D. Pillai
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  • Automated application of low energy electron irradiation enables inactivation of pathogen- and cell-containing liquids in biomedical research and production facilities
    Jasmin Fertey, Martin Thoma, Jana Beckmann, Lea Bayer, Julia Finkensieper, Susann Reißhauer, Beatrice Sarah Berneck, Leila Issmail, Jessy Schönfelder, Javier Portillo Casado, Andre Poremba, Frank-Holm Rögner, Bastian Standfest, Gustavo R. Makert, Lia Walc
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  • Low-Energy Electron Irradiation Efficiently Inactivates the Gram-Negative Pathogen Rodentibacter pneumotropicus—A New Method for the Generation of Bacterial Vaccines with Increased Efficacy
    Jasmin Fertey, Lea Bayer, Sophie Kähl, Rukiya M. Haji, Anke Burger-Kentischer, Martin Thoma, Bastian Standfest, Jessy Schönfelder, Javier Portillo Casado, Frank-Holm Rögner, Christoph Georg Baums, Thomas Grunwald, Sebastian Ulbert
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  • Next-Generation Whole-Cell Pneumococcal Vaccine
    Victor Morais, Esther Texeira, Norma Suarez
    Vaccines.2019; 7(4): 151.     CrossRef
  • Gamma-irradiation-killed Streptococcus pneumoniae potently induces the expression of IL-6 and IL-8 in human bronchial epithelial cells
    Min Yong Jwa, Eun Byeol Ko, Hyun Young Kim, Sun Kyung Kim, Soyoung Jeong, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
    Microbial Pathogenesis.2018; 124: 38.     CrossRef
Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice
Yulan Qiu , Xuemei Zhang , Xinyuan Zhang , Yunjun Mo , Xiaoyu Sun , Jichao Wang , Yibing Yin , Wenchun Xu
J. Microbiol. 2017;55(10):823-829.   Published online September 28, 2017
DOI: https://doi.org/10.1007/s12275-017-7262-1
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AbstractAbstract PDF
diseases in children under 5-year-old. Vaccine has been used as an indispensable strategy to prevent S. pneumoniae infection for more than 30 years. Our previous studies confirmed that mucosal immunization with live attenuated strain SPY1 can protect mice against nasopharyngeal colonization of S. pneumoniae and lethal pneumococcal infection, and the protective effects are comparable with those induced by commercially available 23-valent polysaccharide vaccine. However, live attenuated vaccine SPY1 needs four inoculations to get satisfactory protective effect, which may increase the risk of virulence recovery. It is reported that heterologous primeboost approach is more effective than homologous primeboost approach. In the present study, to decrease the doses of live SPY1 and improve the safety of SPY1 vaccine, we immunized mice with SPY1 and DnaJ protein alternately. Our
results
showed that heterologous prime-boost immunization with SPY1 and DnaJ protein could significantly reduce the colonization of S. pneumoniae in the respiratory tract of mice, and induce stronger Th1 and Th17 cellular immune responses than SPY1 alone. These results indicate heterologous prime-boost immunization method not only elicits better protective effect than SPY1 alone, but also reduces the doses of live SPY1 and decreases the risk of SPY1 vaccine. This work is the first time to study the protective efficiency with two different forms of S. pneumoniae candidate vaccine, and provides a new strategy for the development of S. pneumoniae vaccine.

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  • Recombinant Molecules as a New Frontier in Mucositis Therapy
    Luís Cláudio Lima de Jesus, Rhayane Cristina Viegas Santos, Vasco Azevedo
    BioDrugs.2025;[Epub]     CrossRef
  • Subcutaneous immunization with the fusion protein ΔA146Ply-SP0148 confers protection against Streptococcus pneumoniae infection
    Yao Wang, Lingyin Xia, Guangli Wang, Huifang Lu, Hui Wang, Shilu Luo, Tao Zhang, Song Gao, Jian Huang, Xun Min
    Microbial Pathogenesis.2022; 162: 105325.     CrossRef
  • The imbalance of the Th17/Treg axis following equine ascending placental infection
    C.E Fedorka, H. El-Sheikh Ali, O.F. Walker, K.E. Scoggin, P. Dini, S.C. Loux, M.H.T. Troedsson, B.A. Ball
    Journal of Reproductive Immunology.2021; 144: 103268.     CrossRef
  • Combined prime-boost immunization with systemic and mucosal pneumococcal vaccines based on Pneumococcal surface protein A to enhance protection against lethal pneumococcal infections
    Yue Zhang, Xiaonan Guo, Mengze Guo, Xiaorui Chen, Bo Li, Jinfei Yu, Tiejun Gu, Wei Kong, Yongge Wu
    Immunologic Research.2019; 67(4-5): 398.     CrossRef
  • Protective Regulatory T Cell Immune Response Induced by Intranasal Immunization With the Live-Attenuated Pneumococcal Vaccine SPY1 via the Transforming Growth Factor-β1-Smad2/3 Pathway
    Hongyi Liao, Xiaoqiong Peng, Lingling Gan, Jiafu Feng, Yue Gao, Shenghui Yang, Xuexue Hu, Liping Zhang, Yibing Yin, Hong Wang, Xiuyu Xu
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Research Support, Non-U.S. Gov'ts
Pneumococcal wall teichoic acid is required for the pathogenesis of Streptococcus pneumoniae in murine models
Hongmei Xu , Libin Wang , Jian Huang , Yanqing Zhang , Feng Ma , Jianmin Wang , Wenchun Xu , Xuemei Zhang , Yibing Yin , Kaifeng Wu
J. Microbiol. 2015;53(2):147-154.   Published online January 28, 2015
DOI: https://doi.org/10.1007/s12275-015-4616-4
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AbstractAbstract
Pneumococcal asymptomatic colonization of the respiratory tracts is a major risk for invasive pneumococcal disease. We have previously shown that pneumococcal wall teichoic acid (WTA) was involved in pneumococcal infection of sepsis and adherence to epithelial and endothelial cells. In this study, we investigated the contribution of pneumococcal WTA to bacterial colonization and dissemination in murine models. The result showed that nasopharynx colonizing D39 bacterial cells have a distinct phenotype showing an increased exposure of teichoic acids relative to medium-grown bacteria. The WTA-deficient mutants were impaired in their colonization to the nasopharynx and lungs, and led to a mild inflammation in the lungs at 36 h post-inoculation. Pretreatment of the murine nares with WTA reduced the ability of wild type D39 bacteria to colonize the nasopharynx. In addition, the WTA-deficient strain was impaired in its ability to invade the blood and brain following intranasal administration. WTA-deficient D39 strain was reduced in C3 deposition but was more susceptible to the killing by the neutrophils as compared with its parent strain. Our results also demonstrated that the WTA enhanced pneumococcal colonization and dissemination independently of the host strains. These results indicate that WTA plays an important role in pneumococcal pathogenesis, both in colonization and dissemination processes.

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  • Insight into the structure, biosynthesis, isolation method and biological function of teichoic acid in different gram-positive microorganisms: A review
    Jiarun Han, Xin Zhao, Xilian Zhao, Ping Li, Qing Gu
    International Journal of Biological Macromolecules.2023; 253: 126825.     CrossRef
  • spd1672, a novel in vivo-induced gene, affects inflammatory response in a murine model of Streptococcus pneumoniae infection
    Lingling Gan, Xuemei Zhang, Xiuyu Xu, Wenchun Xu, Chang Lu, Jin Cui, Hong Wang
    Canadian Journal of Microbiology.2018; 64(6): 401.     CrossRef
  • Lipoteichoic acid deficiency permits normal growth but impairs virulence of Streptococcus pneumoniae
    Nathalie Heß, Franziska Waldow, Thomas P. Kohler, Manfred Rohde, Bernd Kreikemeyer, Alejandro Gómez-Mejia, Torsten Hain, Dominik Schwudke, Waldemar Vollmer, Sven Hammerschmidt, Nicolas Gisch
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    Robert T Gale, Eric D Brown
    Current Opinion in Microbiology.2015; 27: 69.     CrossRef
Changes in Gene Expression of Actinobacillus pleuropneumoniae in Response to Anaerobic Stress Reveal Induction of Central Metabolism and Biofilm Formation
Lu Li , Jiawen Zhu , Kui Yang , Zhuofei Xu , Ziduo Liu , Rui Zhou
J. Microbiol. 2014;52(6):473-481.   Published online April 11, 2014
DOI: https://doi.org/10.1007/s12275-014-3456-y
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  • 17 Crossref
AbstractAbstract PDF
Actinobacillus pleuropneumoniae is an important porcine respiratory pathogen causing great economic losses in the pig industry worldwide. Oxygen deprivation is a stress that A. pleuropneumoniae will encounter during both early infection and the later, persistent stage. To understand modulation of A. pleuropneumoniae gene expression in response to the stress caused by anaerobic conditions, gene expression profiles under anaerobic and aerobic conditions were compared in this study. The microarray results showed that 631 genes (27.7% of the total ORFs) were differentially expressed in anaerobic conditions. Many genes encoding proteins involved in glycolysis, carbon source uptake systems, pyruvate metabolism, fermentation and the electron respiration transport chain were up-regulated. These changes led to an increased amount of pyruvate, lactate, ethanol and acetate in the bacterial cells as confirmed by metabolite detection. Genes encoding proteins involved in cell surface structures, especially biofilm formation, peptidoglycan biosynthesis and lipopolysaccharide biosynthesis were up-regulated as well. Biofilm formation was significantly enhanced under anaerobic conditions. These results indicate that induction of central metabolism is important for basic survival of A. pleuropneumoniae after a shift to an anaerobic environment. Enhanced biofilm formation may contribute to the persistence of this pathogen in the damaged anaerobic host tissue and also in the early colonization stage. These discoveries give new insights into adaptation mechanisms of A. pleuropneumoniae in response to environmental stress.

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  • Mycobacteroides abscessus ability to interact with the host mucosal cells plays an important role in pathogenesis of the infection
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    Elena Schreiber, Fritjof Freise, Nicole de Buhr, Isabel Hennig-Pauka
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    Anati Abd Rashid Syaida, Faez Firdaus Abdullah Jesse, Mohd Shafiq Aazmi, Mohd Izwan Mohamad Yusof, Norfatimah Mohamed Yunus, Mohd Fakharul Zaman Raja Yahya
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    Qiuhong Zhang, Hao Tang, Chaoyue Yan, Weiyao Han, Lu Peng, Jiajia Xu, Xiabing Chen, Paul R. Langford, Weicheng Bei, Qi Huang, Rui Zhou, Lu Li, Andreas J. Bäumler
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    Rajoana Rojony, Lia Danelishvili, Anaamika Campeau, Jacob M. Wozniak, David J. Gonzalez, Luiz E. Bermudez
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    Sarah A. Konze, Wolf-Rainer Abraham, Elke Goethe, Esther Surges, Marcel M. M. Kuypers, Doris Hoeltig, Jochen Meens, Charlotte Vogel, Meike Stiesch, Peter Valentin-Weigand, Gerald-F. Gerlach, Falk F. R. Buettner, Sabine Ehrt
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    Skander Hathroubi, Abraham Loera-Muro, Alma L. Guerrero-Barrera, Yannick D. N. Tremblay, Mario Jacques
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    E. L. Sassu, J. T. Bossé, T. J. Tobias, M. Gottschalk, P. R. Langford, I. Hennig-Pauka
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    Elena L. Sassu, Andrea Ladinig, Stephanie C. Talker, Maria Stadler, Christian Knecht, Heiko Stein, Janna Frömbling, Barbara Richter, Joachim Spergser, Monika Ehling-Schulz, Robert Graage, Isabel Hennig-Pauka, Wilhelm Gerner
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  • A Transcriptome Map of Actinobacillus pleuropneumoniae at Single-Nucleotide Resolution Using Deep RNA-Seq
    Zhipeng Su, Jiawen Zhu, Zhuofei Xu, Ran Xiao, Rui Zhou, Lu Li, Huanchun Chen, Ying Xu
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    Boram Lim, Minji Sim, Howoon Lee, Seogang Hyun, Younghoon Lee, Yoonsoo Hahn, Eunkyoung Shin, Kangseok Lee
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    Louise Brogaard, Kirstine Klitgaard, Peter MH Heegaard, Mette Sif Hansen, Tim Kåre Jensen, Kerstin Skovgaard
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  • Identification and characterization of a novel stress-responsive outer membrane protein Lip40 from Actinobacillus pleuropneumoniae
    Xuehe Hu, Hao Yan, Ke Liu, Jiansheng Hu, Chao Qi, Jihong Yang, Yanli Liu, Jin Zhao, Jinlin Liu
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    Maksim Shestov, Santiago Ontañón, Aydin Tozeren
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Serotype-Independent Protection against Pneumococcal Infections Elicited by Intranasal Immunization with Ethanol-Killed Pneumococcal Strain, SPY1
Xiuyu Xu , Jiangping Meng , Yiping Wang , Jie Zheng , Kaifeng Wu , Xuemei Zhang , Yibing Yin , Qun Zhang
J. Microbiol. 2014;52(4):315-323.   Published online March 29, 2014
DOI: https://doi.org/10.1007/s12275-014-3583-5
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AbstractAbstract PDF
The 23-valent polysaccharide vaccine and the 7-valent pneumococcal conjugate vaccine are licensed vaccines that protect against pneumococcal infections worldwide. However, the incidence of pneumococcal diseases remains high in lowincome countries. Whole-cell vaccines with high safety and strong immunogenicity may be a favorable choice. We previously obtained a capsule-deficient Streptococcus pneumoniae mutant named SPY1 derived from strain D39. As an attenuated live pneumococcal vaccine, intranasal immunization with SPY1 elicits broad serotype-independent protection against pneumococcal infection. In this study, for safety consideration, we inactivated SPY1 with 70% ethanol and intranasally immunized BALB/c mice with killed SPY1 plus cholera toxin adjuvant for four times. Results showed that intranasal immunization with inactivated SPY1 induced strong humoral and cellular immune responses. Intranasal immunization with inactivated SPY1 plus cholera toxin adjuvant elicited effective serotype-independent protection against the colonization of pneumococcal strains 19F and 4 as well as lethal infection of pneumococcal serotypes 2, 3, 14, and 6B. The protection rates provided by inactivated SPY1 against lethal pneumococcal infection were comparable to those of currently used polysaccharide vaccines. In addition, vaccinespecific B-cell and T-cell immune responses mediated the protection elicited by SPY1. In conclusion, the 70% ethanolinactivated pneumococcal whole-cell vaccine SPY1 is a potentially safe and less complex vaccine strategy that offers broad protection against S. pneumoniae.

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  • Corrected and Republished from: “A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge”
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  • Non-capsular based immunization approaches to prevent Streptococcus pneumoniae infection
    Pedro H. Silva, Yaneisi Vázquez, Camilo Campusano, Angello Retamal-Díaz, Margarita K. Lay, Christian A. Muñoz, Pablo A. González, Alexis M. Kalergis, Susan M. Bueno
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    Win-Yan Chan, Claire Entwisle, Giuseppe Ercoli, Elise Ramos-Sevillano, Ann McIlgorm, Paola Cecchini, Christopher Bailey, Oliver Lam, Gail Whiting, Nicola Green, David Goldblatt, Jun X. Wheeler, Jeremy S. Brown, Liise-anne Pirofski
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    M. Mohammadzadeh, B. Pourakbari, A. Doosti, S. Mahmoudi, M. Habibi-Anbouhi, S. Mamishi
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  • Gamma-irradiation of Streptococcus pneumoniae for the use as an immunogenic whole cell vaccine
    Min Yong Jwa, Soyoung Jeong, Eun Byeol Ko, A Reum Kim, Hyun Young Kim, Sun Kyung Kim, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
    Journal of Microbiology.2018; 56(8): 579.     CrossRef
  • spd1672, a novel in vivo-induced gene, affects inflammatory response in a murine model of Streptococcus pneumoniae infection
    Lingling Gan, Xuemei Zhang, Xiuyu Xu, Wenchun Xu, Chang Lu, Jin Cui, Hong Wang
    Canadian Journal of Microbiology.2018; 64(6): 401.     CrossRef
  • Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice
    Yulan Qiu, Xuemei Zhang, Hong Wang, Xinyuan Zhang, Yunjun Mo, Xiaoyu Sun, Jichao Wang, Yibing Yin, Wenchun Xu
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  • Panel 6: Vaccines
    Melinda M. Pettigrew, Mark R. Alderson, Lauren O. Bakaletz, Stephen J. Barenkamp, Anders P. Hakansson, Kevin M. Mason, Johanna Nokso‐Koivisto, Janak Patel, Stephen I. Pelton, Timothy F. Murphy
    Otolaryngology–Head and Neck Surgery.2017;[Epub]     CrossRef
  • Attenuated Streptococcus pneumoniae vaccine candidate SPY1 promotes dendritic cell activation and drives a Th1/Th17 response
    Song Gao, Lingbin Zeng, Xuemei Zhang, Yingying Wu, Jingjing Cui, Zhixin Song, Xiaoyu Sun, Hong Wang, Yibing Yin, Wenchun Xu
    Immunology Letters.2016; 179: 47.     CrossRef
  • SEROTYPE-INDEPENDENT VACCINES AGAINST PNEUMOCOCCAL INFECTION
    I. B. Semenova, N. A. Mikhailova
    Journal of microbiology, epidemiology and immunobiology.2016; 93(4): 76.     CrossRef
  • Compound 48/80 acts as a potent mucosal adjuvant for vaccination against Streptococcus pneumoniae infection in young mice
    Lingbin Zeng, Yusi Liu, Hong Wang, Pu Liao, Zhixin Song, Song Gao, Yingying Wu, Xuemei Zhang, Yibing Yin, Wenchun Xu
    Vaccine.2015; 33(8): 1008.     CrossRef
  • Mucosal Immunization with the Live Attenuated Vaccine SPY1 Induces Humoral and Th2-Th17-Regulatory T Cell Cellular Immunity and Protects against Pneumococcal Infection
    Xiuyu Xu, Hong Wang, Yusi Liu, Yiping Wang, Lingbing Zeng, Kaifeng Wu, Jianmin Wang, Feng Ma, Wenchun Xu, Yibing Yin, Xuemei Zhang, A. Camilli
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Characterization of Streptococcus pneumoniae N-Acetylglucosamine-6-Phosphate Deacetylase as a Novel Diagnostic Marker
Chi-Won Choi , Hee-Young An , Yong Ju Lee , Yeol Gyun Lee , Sung Ho Yun , Edmond Changkyun Park , Yeonhee Hong , Gun-Hwa Kim , Jae-Eun Park , Sun Jong Baek , Hyun Sik Kim , Seung Il Kim
J. Microbiol. 2013;51(5):659-664.   Published online October 31, 2013
DOI: https://doi.org/10.1007/s12275-013-3451-8
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AbstractAbstract PDF
The identification of novel diagnostic markers of pathogenic bacteria is essential for improving the accuracy of diagnoses and for developing targeted vaccines. Streptococcus pneumoniae is a significant human pathogenic bacterium that causes pneumonia. N-acetylglucosamine-6-phosphate deacetylase (NagA) was identified in a protein mixture secreted by S. pneumoniae and its strong immunogenicity was confirmed in an immuno-proteomic assay against the anti-serum of the secreted protein mixture. In this study, recombinant S. pneumoniae NagA protein was expressed and purified to analyze its protein characteristics, immunospecificity, and immunogenicity, thereby facilitating its evaluation as a novel diagnostic marker for S. pneumoniae. Mass spectrometry analysis showed that S. pneumoniae NagA contains four internal disulfide bonds and that it does not undergo posttranslational modification. S. pneumoniae NagA antibodies successfully detected NagA from different S. pneumoniae strains, whereas NagA from other pathogenic bacteria species was not detected. In addition, mice infected with S. pneumoniae generated NagA antibodies in an effective manner. These results suggest that NagA has potential as a novel diagnostic marker for S. pneumoniae because of its high immunogenicity and immunospecificity.

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  • Multi-omic profiling to assess the effect of iron starvation inStreptococcus pneumoniaeTIGR4
    Irene Jiménez-Munguía, Mónica Calderón-Santiago, Antonio Rodríguez-Franco, Feliciano Priego-Capote, Manuel J. Rodríguez-Ortega
    PeerJ.2018; 6: e4966.     CrossRef
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    Qingzhou Cheng, Lijuan Wu, Rongfu Tu, Jun Wu, Wenqian Kang, Tong Su, Runlei Du, Wenbin Liu
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    Sarah Teatero, Patricia Ferrieri, Nahuel Fittipaldi
    Emerging Infectious Diseases.2016; 22(11): 1937.     CrossRef
  • Mass Spectrometry in Clinical Microbiology and Infectious Diseases
    Frank Fleurbaaij, Hans C. van Leeuwen, Oleg I. Klychnikov, Ed J. Kuijper, Paul J. Hensbergen
    Chromatographia.2015; 78(5-6): 379.     CrossRef
Screening and Identification of ClpE Interaction Proteins in Streptococcus pneumoniae by a Bacterial Two-Hybrid System and Co-immunoprecipitation
WenJuan Yan , YingYing Cai , Qun Zhang , YuSi Liu , WenChun Xu , YiBing Yin , YuJuan He , Hong Wang , XueMei Zhang
J. Microbiol. 2013;51(4):453-460.   Published online August 30, 2013
DOI: https://doi.org/10.1007/s12275-013-3001-4
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AbstractAbstract PDF
Hsp100/Clp proteins have crucial functions in the protein quality control, stress tolerance, and virulence of many pathogenic bacteria. ClpE is an important virulence factor involved in adherence and invasion in Streptococcus pneumoniae. To explore the underlying mechanism, we screened ClpE interaction proteins using a bacterial two-hybrid system and co-immunoprecipitation. We used ClpE as bait and constructed the pBT-ClpE bait plasmid for two-hybrid screening. Then, we constructed ClpE::GFP fusion for co-immunoprecipitation screening using anti-GFP monoclonal antibody. We obtained eight potential ClpE interaction proteins, including carbamoyl-phosphate synthase, pyruvate oxidase (SpxB), phosphoenolpyruvate-protein phosphotransferase, aminopeptidase N (pepN), L-lactate dehydrogenase, ribosomal protein S4, sensor histidine kinase (SPD_2019), and FtsW (a cell division protein). FtsW, SpxB, pepN, and SPD_2019 were confirmed to interact with ClpE using Bacterial Two-hybrid or Co-immunoprecipitation. Morphologic observations found that ΔclpE strain existed in abnormal division. β-Galactosidase activity assay suggested that ClpE contributed to the degradation of FtsW. Furthermore, FtsW could be induced by heat shock. The results suggested that ClpE might affect cell division by regulating the level of FtsW. These data may provide new insights in studying the role of ClpE in S. pneumoniae.

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  • Legume nodulation and nitrogen fixation require interaction of DnaJ-like protein and lipid transfer protein
    Dasong Chen, Dongzhi Li, Ziqi Li, Yuting Song, Qingsong Li, Lihong Wang, Donglai Zhou, Fuli Xie, Youguo Li
    Plant Physiology.2023; 193(3): 2164.     CrossRef
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    Ling Wang, Xuemei Zhang, Guangying Wu, Yuhong Qi, Jinghui Zhang, Jing Yang, Hong Wang, Wenchun Xu
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    Bin Li, Xiaoxuan Wang, Jie Chen, He Liu, Khattak Arif Ali, Yanli Wang, Wen Qiu, Guochang Sun
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  • Antibacterial effects of Traditional Chinese Medicine monomers against Streptococcus pneumoniae via inhibiting pneumococcal histidine kinase (VicK)
    Shuai Zhang, Jianmin Wang, Wenchun Xu, Yusi Liu, Wei Wang, Kaifeng Wu, Zhe Wang, Xuemei Zhang
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Identification of Conserved Surface Proteins as Novel Antigenic Vaccine Candidates of Actinobacillus pleuropneumoniae
Xiabing Chen , Zhuofei Xu , Lu Li , Huanchun Chen , Rui Zhou
J. Microbiol. 2012;50(6):978-986.   Published online December 30, 2012
DOI: https://doi.org/10.1007/s12275-012-2214-2
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AbstractAbstract PDF
Actinobacillus pleuropneumoniae is an important swine respiratory pathogen causing great economic losses worldwide. Identification of conserved surface antigenic proteins is helpful for developing effective vaccines. In this study, a genome-wide strategy combined with bioinformatic and experimental approaches, was applied to discover and characterize surface-associated immunogenic proteins of A. pleuropneumoniae. Thirty nine genes encoding outer membrane proteins (OMPs) and lipoproteins were identified by comparative genomics and gene expression profiling as beinghighly conserved and stably transcribed in the different serotypes of A. pleuropneumoniae reference strains. Twelve of these conserved proteins were successfully expressed in Escherichia coli and their immunogenicity was estimated by homologous challenge in the mouse model, and then three of these proteins (APJL_0126, HbpA and OmpW) were further tested in the natural host (swine) by homologous and heterologous challenges. The results showed that these proteins could induce high titers of antibodies, but vaccination with each protein individually elicited low protective immunity against A. pleuropneumoniae. This study gives novel insights into immunogenicity of the conserved OMPs and lipoproteins of A. pleuropneumoniae. Although none of the surface proteins characterized in this study could individually induce effective protective immunity against A. pleuropneumoniae, they are potential candidates for subunit vaccines in combination with Apx toxins.

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  • Identification of candidate vaccine antigens using 2-D gel electrophoresis and immunoproteomics for cross protection against Glaesserella parasuis
    Samantha J. Hau, Kirsten C. Eberle, Jarlath E. Nally, Daniel W. Nielsen, John D. Lippolis, Susan L. Brockmeier
    Veterinary Microbiology.2025; 307: 110594.     CrossRef
  • Review of advanced research on swine Actinobacillus pleuropneumoniae vaccine development strategy
    Adehanom Baraki Tesfaye, Rui Han, Zhengyu Tao, Liuchao You, Jiayao Zhu, Pengcheng Gao, Lei Fu, Yuefeng Chu
    Frontiers in Immunology.2025;[Epub]     CrossRef
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    Jinyue Yang, Xueting Zhang, Junhua Dong, Qian Zhang, Erchao Sun, Cen Chen, Zhuangxia Miao, Yifei Zheng, Nan Zhang, Pan Tao
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Identification of a Novel Linear B-Cell Epitope of HbpA Protein from Glaesserella parasuis Using Monoclonal Antibody
    Geyan Liu, Kang Wang, Zhen Yang, Xiaoyu Tang, Yung-Fu Chang, Ke Dai, Xinwei Tang, Bangdi Hu, Yiwen Zhang, Sanjie Cao, Xiaobo Huang, Qigui Yan, Rui Wu, Qin Zhao, Senyan Du, Xintian Wen, Yiping Wen
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  • Proteomic and immunoproteomic insights into the exoproteome of Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia
    Stelli G. Stancheva, Janna Frömbling, Elena L. Sassu, Isabel Hennig-Pauka, Andrea Ladinig, Wilhelm Gerner, Tom Grunert, Monika Ehling-Schulz
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  • Genome-wide screening of lipoproteins in Actinobacillus pleuropneumoniae identifies three antigens that confer protection against virulent challenge
    Yurou Cao, Lulu Gao, Li Zhang, Lixiang Zhou, Jihong Yang, Lingfu Deng, Jin Zhao, Chao Qi, Jinlin Liu
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    Tingting Li, Qiuhong Zhang, Rong Wang, Sihua Zhang, Jie Pei, Yaokun Li, Lu Li, Rui Zhou
    Microbial Pathogenesis.2019; 126: 310.     CrossRef
  • Recombinant ApxIV protein enhances protective efficacy againstActinobacillus pleuropneumoniaein mice and pigs
    H.-C. Wu, P.-H. Yeh, K.-J. Hsueh, W.-J. Yang, C.-Y. Chu
    Journal of Applied Microbiology.2018; 124(6): 1366.     CrossRef
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    Abraham Loera-Muro, Carlos Angulo
    Veterinary Microbiology.2018; 217: 66.     CrossRef
  • A trivalent Apx-fusion protein delivered by E. coli outer membrane vesicles induce protection against Actinobacillus pleuropneumoniae of serotype 1 and 7 challenge in a murine model
    Kui Xu, Qin Zhao, Xintian Wen, Rui Wu, Yiping Wen, Xiaobo Huang, Yong Huang, Qigui Yan, Xinfeng Han, Xiaoping Ma, Yung-Fu Chang, Sanjie Cao, Utpal Pal
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  • Identification and characterization of a novel stress-responsive outer membrane protein Lip40 from Actinobacillus pleuropneumoniae
    Xuehe Hu, Hao Yan, Ke Liu, Jiansheng Hu, Chao Qi, Jihong Yang, Yanli Liu, Jin Zhao, Jinlin Liu
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    Luhua Zhang, Yiping Wen, Ying Li, Xingliang Wei, Xuefeng Yan, Xintian Wen, Rui Wu, Xiaobo Huang, Yong Huang, Qigui Yan, Mafeng Liu, Sanjie Cao
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SP0454, A Putative Threonine Dehydratase, Is Required For Pneumococcal Virulence In Mice
WenJuan Yan , Hong Wang , WenChun Xu , KaiFeng Wu , Run Yao , XiuYu Xu , Jie Dong , YanQing Zhang , Wen Zhong , XueMei Zhang
J. Microbiol. 2012;50(3):511-517.   Published online June 30, 2012
DOI: https://doi.org/10.1007/s12275-012-2014-8
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AbstractAbstract PDF
Increasing pressure in antibiotic resistance and the requirement for the design of new vaccines are the objectives of clarifying the putative virulence factors in pneumococcal infection. In this study, the putative threonine dehydratase sp0454 was inactivated by erythromycin-resistance cassette replacement in Streptococcus pneumoniae CMCC 31203 strain. The sp0454 mutant was tested for cell growth, adherence, colonization, and virulence in a murine model. The Δsp0454 mutant showed decreased ability for colonization and impaired ability to adhere to A549 cells. However, the SP0454 polypeptide or its antiserum did not affect pneumococcal CMCC 31203 adhesion to A549 cells. The sp0454 deletion mutant was less virulent in a murine intranasal infection model. Real-time RT-PCR analysis revealed significant decrease of the pneumococcal surface antigen A expression in the sp0454 mutant. These results suggest that SP0454 contributes to virulence and colonization, which could be explained in part by modulating the expression of other virulence factors, such as psaA in pneumococcal infection.

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    Yulan Qiu, Xuemei Zhang, Hong Wang, Xinyuan Zhang, Yunjun Mo, Xiaoyu Sun, Jichao Wang, Yibing Yin, Wenchun Xu
    Journal of Microbiology.2017; 55(10): 823.     CrossRef
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    Xiuyu Xu, Hong Wang, Yusi Liu, Yiping Wang, Lingbing Zeng, Kaifeng Wu, Jianmin Wang, Feng Ma, Wenchun Xu, Yibing Yin, Xuemei Zhang, A. Camilli
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    Xiuyu Xu, Jiangping Meng, Yiping Wang, Jie Zheng, Kaifeng Wu, Xuemei Zhang, Yibing Yin, Qun Zhang
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Berberine Inhibits HEp-2 Cell Invasion Induced by Chlamydophila pneumoniae Infection
Li Jun Zhang , Li Jun Zhang , Wei Quan , Bei Bei Wang , Bing Ling Shen , Teng Teng Zhang , Yi Kang
J. Microbiol. 2011;49(5):834-840.   Published online November 9, 2011
DOI: https://doi.org/10.1007/s12275-011-1051-z
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AbstractAbstract PDF
This study investigated the inhibitory effects of berberine on Chlamydophila (Chlamydia) pneumoniae infection-induced HEp-2 cell invasion and explored the possible mechanisms involved in this process. C. pneumoniae infection resulted in a significant increase in HEp-2 cell invasion when compared with the control cells (P<0.01) in a Matrigel invasion assay. This enhanced cell invasion was strongly suppressed by berberine (50 μM) (P<0.01). In a cell adhesion assay, the infection-induced HEp-2 cell adhesion to Matrigel was also significantly inhibited by berberine (P<0.01). C. pneumoniae infection was found to promote HEp-2 cell migration remarkably (P<0.01), which was markedly suppressed by berberine (P<0.01) in the cell migration assays. There were no statistically significant differences in the expression of matrix metalloproteinase-1 (MMP-1) and MMP-9 in the infected cells and berberine did not change the expression of MMP-1 and MMP-9. These data suggest that berberine inhibits C. pneumoniae infection-induced HEp-2 cell invasion through suppressing HEp-2 cell adhesion and migration, but not through changing the expression of MMP-1 and MMP-9.

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  • Berberine and its nanoformulations and extracts: potential strategies and future perspectives against multi-drug resistant bacterial infections
    Xue Yang, Yanfen Wang, Ling Li, Daiyan Tang, Zhong Yan, MingYan Li, Jiayi Jiang, Dongming Bi
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    Effie E. Bastounis, Prathima Radhakrishnan, Christopher K. Prinz, Julie A. Theriot
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    Lu Ma, Lijun Zhang, Beibei Wang, Junyan Wei, Jingya Liu, Lijun Zhang
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    Ning Sun, Fung-Yi Chan, Yu-Jing Lu, Marco A. C. Neves, Hok-Kiu Lui, Yong Wang, Ka-Yan Chow, Kin-Fai Chan, Siu-Cheong Yan, Yun-Chung Leung, Ruben Abagyan, Tak-Hang Chan, Kwok-Yin Wong, Dirk-Jan Scheffers
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    Junxia Zhang, Haiwei Wang, Lijun Zhang, Tengteng Zhang, Beibei Wang, Xiankui Li, Junyan Wei, Lijun Zhang
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    Beibei Wang, Lijun Zhang, Tengteng Zhang, Haiwei Wang, Junxia Zhang, Junyan Wei, Bingling Shen, Xin Liu, Zhelong Xu, Lijun Zhang, R. P. Morrison
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Molecular Analysis of a Prolonged Spread of Klebsiella pneumoniae Co-producing DHA-1 and SHV-12 β-Lactamases
Young Kyung Yoon , Hye Won Cheong , Hyunjoo Pai , Kyoung Ho Roh , Jeong Yeon Kim , Dae Won Park , Jang Wook Sohn , Seung Eun Lee , Byung Chul Chun , Hee Sun Sim , Min Ja Kim
J. Microbiol. 2011;49(3):363-368.   Published online June 30, 2011
DOI: https://doi.org/10.1007/s12275-011-0491-9
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AbstractAbstract PDF
The study investigated molecular mechanisms for prolonged nosocomial spread of multidrug-resistant Klebsiella pneumoniae co-producing plasmid-mediated AmpC β-lactamase DHA-1 and extended-spectrum β-lactamase SHV-12. Forty-eight clinical isolates of K. pneumonia, resistant to the extended-spectrum cephalosporins, were collected in a 750-bed university hospital over a year. The isolates were characterized for PCR-based β-lactamase genotypes, isoelectric focusing and pulsed-field gel electrophoresis (PFGE) profiles. Resistance transfer was performed by plasmid conjugation and confirmed by a duplex-PCR and Southern hybridization. On β-lactamase typing, the strains producing only the DHA-1 enzyme (n=17) or co-producing DHA-1 and SHV-12 enzymes (n=15) were predominant. Judging from a one year-distribution of PFGE profiles, the co-producer was spread primarily with single clonal expansion of the PFGE-type A with subtypes (n=14), whereas the strains producing only DHA-1 enzyme were spread simultaneously with the PFGE-type A (n=11) and other PFGE types (n=6). Transconjugants of the co-producers were confirmed to harbor either both blaDHA-1 and blaSHV-12 or only the blaDHA-1. In conclusion, this study indicated that the persistent nosocomial spread of multidrug-resistant K. pneumoniae strains was primarily associated with expansion of a clone harboring both the blaDHA-1 and blaSHV-12 or the blaDHA-1 only, and to a lesser extent with the horizontal transfer of the resistant plasmids. Our observations have clinical implication for the control and prevention of nosocomial dissemination of multidrug-resistant K. pneumoniae strains.

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  • High Prevalence of CTX-M-15-Type Extended-Spectrum β-Lactamase Among AmpC β-Lactamase-Producing Klebsiella pneumoniae Isolates Causing Bacteremia in Korea
    Min Kyeong Cha, Cheol-In Kang, So Hyun Kim, Doo Ryeon Chung, Kyong Ran Peck, Nam Yong Lee, Jae-Hoon Song
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Predicting Genetic Traits and Epitope Analysis of apxIVA in Actinobacillus pleuropneumoniae
Min-Kyoung Shin , Seung-Bin Cha , Won-Jung Lee , Han Sang Yoo
J. Microbiol. 2011;49(3):462-468.   Published online June 30, 2011
DOI: https://doi.org/10.1007/s12275-011-0449-y
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AbstractAbstract PDF
Actinobacillus pleuropneumoniae causes a severe hemorrhagic pneumonia in pigs. Fifteen serotypes of A. pleuropneumoniae express four different Apx toxins that belong to the pore-forming repeats-in-toxin (RTX) group of toxins. ApxIV, which is conserved and up-regulated in vivo, could be an excellent candidate for the development of a protective cross-serotype immunity vaccine, and could aid in the differential diagnosis of diseases caused by A. pleuropneumoniae. We identified and sequenced apxIVA from A. pleuropneumoniae serotype 2 isolated in Korea (Kor-ApxIVA). The Kor-ApxIVA was closely related to Switzerland (AF021919), China (CP000687), and China (GQ332268), showing 98.6%, 98.4%, and 97.2% amino acid homology, respectively. The level of amino acid homology, however, was higher than the nucleotide homology. The structural characteristics of ApxIVA showed RTX proteins, including N-terminal hydrophobic domains, signature sequences for potential acylation sites, and repeated glycine-rich nonapeptides in the C-terminal region of the protein. Thirty glycine-rich nonapeptides with the consensus sequence, L/V-X-G-G-X-G-N/D-D-X, were found in the C-terminus of the Kor-ApxIVA. In addition, the Kor-ApxIVA was predicted for the linear B-cell epitopes and conserved domains with determined peptide sequences. This genetic analysis of the Kor-ApxIVA might be an important foundation for future biological and functional research on ApxIVA.

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  • Review of advanced research on swine Actinobacillus pleuropneumoniae vaccine development strategy
    Adehanom Baraki Tesfaye, Rui Han, Zhengyu Tao, Liuchao You, Jiayao Zhu, Pengcheng Gao, Lei Fu, Yuefeng Chu
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    Ihsan Ullah, Eun-Kyung Jang, Min-Sung Kim, Jin-Ho Shin, Gun-Seok Park, Abdur Khan, Sung-Jun Hong, Byung-Kwon Jung, JungBae Choi, YeongJun Park, Yunyoung Kwak, Jae-Ho Shin
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NOTE] Analysis of Cytoplasmic Membrane Proteome of Streptococcus pneumoniae by Shotgun Proteomic Approach
Chi-Won Choi , Sung-Ho Yun , Sang-Oh Kwon , Sun-Hee Leem , Jong-Soon Choi , Chi-Young Yun , Seung Il Kim
J. Microbiol. 2010;48(6):872-876.   Published online January 9, 2011
DOI: https://doi.org/10.1007/s12275-010-0220-9
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AbstractAbstract PDF
In this study, cytoplasmic membrane proteins of S. pneumoniae strain R6 (ATCC BBA-255) were effectively separated from cell wall or extracellular proteins by sodium carbonate precipitation (SCP) and ultracentrifugation. Forty seven proteins were analyzed as cytoplasmic membrane proteins from the 260 proteins identified by the shotgun proteomic method using SDS-PAGE/LC/MS-MS. ABC transporters for metabolites such as metals, oligopeptides, phosphate, sugar, and amino acids, and membrane proteins involved in phosphotransferse systems, were identified as the predominant and abundant, cytoplasmic membrane proteins that would be essential for nutrient uptake, antibiotic resistance and virulence mechanisms. Our result supports that gel-based shotgun proteomics combined with sodium carbonate precipitation and ultracentrifugation is an effective method for analysis of cytoplasmic membrane proteins of S. pneumoniae.

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    Thomas Pribyl, Martin Moche, Annette Dreisbach, Jetta J.E. Bijlsma, Malek Saleh, Mohammed R. Abdullah, Michael Hecker, Jan Maarten van Dijl, Dörte Becher, Sven Hammerschmidt
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    Diagnostic Microbiology and Infectious Disease.2012; 72(4): 318.     CrossRef
Role of Hydrogen Generation by Klebsiella pneumoniae in the Oral Cavity
Tomoko Kanazuru , Eisuke F. Sato , Kumiko Nagata , Hiroshi Matsui , Kunihiko Watanabe , Emiko Kasahara , Mika Jikumaru , June Inoue , Masayasu Inoue
J. Microbiol. 2010;48(6):778-783.   Published online January 9, 2011
DOI: https://doi.org/10.1007/s12275-010-0149-z
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AbstractAbstract PDF
Some gastrointestinal bacteria synthesize hydrogen (H2) by fermentation. Despite the presence of bactericidal factors in human saliva, a large number of bacteria also live in the oral cavity. It has never been shown that oral bacteria also produce H2 or what role H2 might play in the oral cavity. It was found that a significant amount of H2 is synthesized in the oral cavity of healthy human subjects, and that its generation is enhanced by the presence of glucose but inhibited by either teeth brushing or sterilization with povidone iodine. These observations suggest the presence of H2-generating bacteria in the oral cavity. The screening of commensal bacteria in the oral cavity revealed that a variety of anaerobic bacteria generate H2. Among them, Klebsiella pneumoniae (K. pneumoniae) generated significantly large amounts of H2 in the presence of glucose. Biochemical analysis revealed that various proteins in K. pneumoniae are carbonylated under standard culture conditions, and that oxidative stress induced by the presence of Fe++ and H2O2 increases the number of carbonylated proteins, particularly when their hydrogenase activity is inhibited by KCN. Inhibition of H2 generation markedly suppresses the growth of K. pneumoniae. These observations suggest that H2 generation and/or the reduction of oxidative stress is important for the survival and growth of K. pneumoniae in the oral cavity.

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    Wei Nie, Hao Tang, Zheng Fang, Jiquan Chen, Haili Chen, Qingyu Xiu
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Heterogeneous Virulence Potential and High Antibiotic Resistance of Pseudomonas aeruginosa Strains Isolated from Korean Pneumonia Patients
Mi Young Yoon , Kang-Mu Lee , Seok Hoon Jeong , Jungmin Kim , Sang Sun Yoon
J. Microbiol. 2010;48(4):518-525.   Published online August 20, 2010
DOI: https://doi.org/10.1007/s12275-010-9388-2
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AbstractAbstract PDF
Pseudomonas aeruginosa is an opportunistic human pathogen of clinical importance that causes airway infections in immunocompromised patients. Here, we report the virulence-associated characteristics of strains of P. aeruginosa, isolated from the sputa of 25 Korean pneumonia patients. A high degree of genomic plasticity was observed by random amplified polymorphic DNA genotype analysis, suggesting that the infections were caused by strains with diverse genomic backgrounds. Biofilm formation of each isolate was heterogeneous in terms of their relative motilities. In addition, 48% of isolates were defective in the production of 3-oxo-C12-HSL (PAI-1), a quorum sensing signal molecule. In these strains, PAI-1-dependent elastase production was correspondingly decreased, suggesting that a large number of strains were presumed to be quorum sensing deficient. Multidrug resistance (MDR) was seen in 56% of the isolates tested, and 44% of the MDR strains were resistant to five or more antibiotics. Taken together, our results provide additional insights into the virulence traits of P. aeruginosa clinical isolates, which will aid in treating P. aeruginosa infections in pneumonia patients.

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  • Virulence Characteristics and an Action Mode of Antibiotic Resistance in Multidrug-Resistant Pseudomonas aeruginosa
    Wontae Hwang, Sang Sun Yoon
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    Keehoon Lee, Kang-Mu Lee, Junhyeok Go, Jae-Chan Ryu, Ji-Hwan Ryu, Sang Sun Yoon, Klaus Hantke
    FEMS Microbiology Letters.2016; 363(11): fnw104.     CrossRef
  • A single gene of a commensal microbe affects host susceptibility to enteric infection
    Mi Young Yoon, Kyung Bae Min, Kang-Mu Lee, Yujin Yoon, Yaeseul Kim, Young Taek Oh, Keehoon Lee, Jongsik Chun, Byung-Yong Kim, Seok-Hwan Yoon, Insuk Lee, Chan Yeong Kim, Sang Sun Yoon
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    Kang-Mu Lee, Mi Young Yoon, Yongjin Park, Joon-Hee Lee, Sang Sun Yoon, B. A. McCormick
    Infection and Immunity.2011; 79(7): 2792.     CrossRef
Virulence Attenuation of Streptococcus pneumoniae clpP Mutant by Sensitivity to Oxidative Stress in Macrophages via an NO-Mediated Pathway
Chul-Yong Park , Eun-Hye Kim , Sang-Yoon Choi , Thao Dang-Hien Tran , In-Hye Kim , Su-Nam Kim , Suhkneung Pyo , Dong-Kwon Rhee
J. Microbiol. 2010;48(2):229-235.   Published online May 1, 2010
DOI: https://doi.org/10.1007/s12275-010-9300-0
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AbstractAbstract PDF
ClpP protease is essential for virulence and survival under stress conditions in several pathogenic bacteria. The clpP mutation in a murine infection model has demonstrated both attenuation of virulence and a sensitivity to hydrogen peroxide. However, the underlying mechanisms for these changes have not been resolved. Because macrophages play a major role in immune response and activated macrophages can kill microbes via oxygen-dependant mechanisms, we investigated the effect of the clpP mutation on its sensitivity to macrophage-mediated oxygen-dependant mechanisms. The clpP mutant derived from D39 (serotype 2) exhibited a higher sensitivity to oxidative stresses such as reactive oxygen intermediates, reactive nitrogen intermediates, and H2O2, but no sensitivity to osmotic stress (NaCl) and pH. Moreover, viability of the clpP mutant was significantly increased in murine macrophage cells by treatment with S-methylisothiourea sulfate, which inhibits inducible nitric oxide synthase (iNOS) activity and subsequently elicits lower level secretions of nitric oxide (NO). However, viability of wild type was unchanged. Taken together, these results indicate that ClpP is involved in the resistance to oxidative stresses after entrapment by macrophages and subsequently contributes to virulence via NO mediated pathway.

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  • The ClpXP protease and the ClpX unfoldase control virulence, cell division, and autolysis in Streptococcus pneumoniae
    Viktor H. Mebus, Supradipta De, Larissa M. Busch, Manuela Gesell Salazar, Rabea Schlüter, Uwe Völker, Sven Hammerschmidt, Dorte Frees, Carlos J. Blondel
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  • The oxidative stress response of Streptococcus pneumoniae: its contribution to both extracellular and intracellular survival
    Mirelys Hernandez-Morfa, Nadia B. Olivero, Victoria E. Zappia, German E. Piñas, Nicolas M. Reinoso-Vizcaino, Melina B. Cian, Mariana Nuñez-Fernandez, Paulo R. Cortes, Jose Echenique
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    Mary E. Marquart
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    Jinxin Zheng, Yang Wu, Zhiwei Lin, Guangfu Wang, Sibo Jiang, Xiang Sun, Haopeng Tu, Zhijian Yu, Di Qu
    BMC Microbiology.2020;[Epub]     CrossRef
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    Gerardo García-González, Gloria María González, José P. Palma-Nicolás
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    Carlos Moreno-Cinos, Kenneth Goossens, Irene G. Salado, Pieter Van Der Veken, Hans De Winter, Koen Augustyns
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  • Biological and Chemical Adaptation to Endogenous Hydrogen Peroxide Production in Streptococcus pneumoniae D39
    John P. Lisher, Ho-Ching Tiffany Tsui, Smirla Ramos-Montañez, Kristy L. Hentchel, Julia E. Martin, Jonathan C. Trinidad, Malcolm E. Winkler, David P. Giedroc, Craig D. Ellermeier
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    Shabnam Sadoogh Abbasian, Ehsanollah Ghaznavi Rad, Neda Akbari, Mohammad Reza Zolfaghari, Iraj pakzad, Hamid Abtahi
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    Hasan Yesilkaya, Vahid Farshchi Andisi, Peter W. Andrew, Jetta J.E. Bijlsma
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    Jun-Oh Lee, Ji-Yun Kim, Dong-Kwon Rhee, Suhkneung Pyo
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  • Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress
    Vahid Farshchi Andisi, Cecilia A. Hinojosa, Anne de Jong, Oscar P. Kuipers, Carlos J. Orihuela, Jetta J. E. Bijlsma, J. N. Weiser
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    Tiffany Vinckx, Qing Wei, Sandra Matthijs, Jean-Paul Noben, Ruth Daniels, Pierre Cornelis
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Prediction of Bacterial Proteins Carrying A Nuclear Localization Signal and Nuclear Targeting of HsdM from Klebsiella pneumoniae
Je Chul Lee , Dong Sun Kim , Dong Chan Moon , Jung-Hwa Lee , Mi Jin Kim , Su Man Lee , Yong Seok Lee , Se-Won Kang , Eun Jung Lee , Sang Sun Kang , Eunpyo Lee , Sung Hee Hyun
J. Microbiol. 2009;47(5):641-645.   Published online October 24, 2009
DOI: https://doi.org/10.1007/s12275-009-0217-4
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AbstractAbstract PDF
Nuclear targeting of bacterial proteins is an emerging pathogenic mechanism whereby bacterial proteins can interact with nuclear molecules and alter the physiology of host cells. The fully sequenced bacterial genome can predict proteins that target the nuclei of host cells based on the presence of nuclear localization signal (NLS). In the present study, we predicted bacterial proteins with the NLS sequences from Klebsiella pneumoniae by bioinformatic analysis, and 13 proteins were identified as carrying putative NLS sequences. Among them, HsdM, a subunit of KpnAI that is a type I restriction-modification system found in K. pneumoniae, was selected for the experimental proof of nuclear targeting in host cells. HsdM carried the NLS sequences, 7KKAKAKK13, in the N-terminus. A transient expression of HsdM-EGFP in COS-1 cells exhibited exclusively a nuclear localization of the fusion proteins, whereas the fusion proteins of HsdM with substitutions in residues lysine to alanine in the NLS sequences, 7AAAKAAA13, were localized in the cytoplasm. HsdM was co-localized with importin α in the nuclei of host cells. Recombinant HsdM alone methylated the eukaryotic DNA in vitro assay. Although HsdM tested in this study has not been considered to be a virulence factor, the prediction of NLS motifs from the full sequenced genome of bacteria extends our knowledge of functional genomics to understand subcellular targeting of bacterial proteins.
Journal Articles
Development of a Method Based on Surface Enhanced Laser Desorption and Ionization Time of Flight Mass Spectrometry for Rapid Identification of Klebsiella pneumoniae
Daiwen Xiao , Yongchang Yang , Hua Liu , Hua Yu , Yingjun Yan , Wenfang Huang , Wei Jiang , Weijin Liao , Qi Hu , Bo Huang
J. Microbiol. 2009;47(5):646-650.   Published online October 24, 2009
DOI: https://doi.org/10.1007/s12275-009-0092-z
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AbstractAbstract PDF
A method based on surface enhanced laser desorption and ionization time of flight mass spectrometry (SELDI-TOF MS) was developed for the rapid identification of Klebsiella pneumoniae by directly applying bacterial colonies without further protein extraction. A total of 40 K. pneumoniae and 114 other related microorganisms isolated clinically were analyzed by SELDI-TOF MS. An identification model for K. pneumoniae was established by artificial neural networks (ANNs) with classification accuracy of 100%. The model was blindly tested with 43 K. pneumoniae and 53 control bacteria again. The results showed that the model was successful with accuracy of 96.9%, sensitivity of 100% and specificity of 94.3%. This strategy is potential for rapid identification of K. pneumoniae.

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  • Direct common gram-negative bacterial identification from positive blood culture bottles by SELDI-TOF MS
    Daiwen Xiao, Yongchang Yang, Wei Jiang, Hangfeng Zhang, Hua Liu, Hua Yu, Chunbao Xie, Min Zhong, Liang Chen, Wenfang Huang
    Journal of Microbiological Methods.2014; 105: 116.     CrossRef
  • Advances in mass spectrometry for the identification of pathogens
    Yen‐Peng Ho, P. Muralidhar Reddy
    Mass Spectrometry Reviews.2011; 30(6): 1203.     CrossRef
Proteomic Analysis of Protein Expression in Streptococcus pneumoniae in Response to Temperature Shift
Myoung-Ro Lee , Song-Mee Bae , Tong-Soo Kim , Kwang-Jun Lee
J. Microbiol. 2006;44(4):375-382.
DOI: https://doi.org/2417 [pii]
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AbstractAbstract PDF
From its initial colonization to causation of disease, Streptococcus pneumoniae has evolved strategies to cope with a number of stressful in vivo environmental conditions. In order to analyze a global view of this organism’s response to heat shock, we established a 2-D electrophoresis proteome map of the S. pneumoniae D39 soluble proteins under in vitro culture conditions and performed the comparative proteome analysis to a 37 to 42°C temperature up-shift in S. pneumoniae. When the temperature of an exponentially growing S. pneumoniae D39 culture was raised to 42°C, the expression level of 25 proteins showed changes when compared to the control. Among these 25 proteins, 12 were identified by MALDI-TOF and LC-coupled ESI MS/MS. The identified proteins were shown to be involved in the general stress response, energy metabolism, nucleotide biosynthesis pathways, and purine metabolism. These results provide clues for understanding the mechanism of adaptation to heat shock by S. pneumoniae and may facilitate the assessment <br>of a possible role for these proteins in the physiology and pathogenesis of this pathogen.
Research Support, U.S. Gov't, Non-P.H.S.
Utilization of Putrescine by Streptococcus pneumoniae During Growth in Choline-limited Medium
D. Ware , J. Watt , E. Swiatlo
J. Microbiol. 2005;43(5):398-405.
DOI: https://doi.org/2284 [pii]
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AbstractAbstract PDF
Polyamines such as putrescine are small, ubiquitous polycationic molecules that are required for optimal growth of eukaryotic and prokaryotic cells. These molecules have diverse effects on cell physiology and their intracellular content is regulated by de novo synthesis and uptake from the environment. The studies presented here examined the structure of a putative polyamine transporter (Pot) operon in Streptococcus pneumoniae (pneumococcus) and growth of pneumococci in medium containing putrescine substituted for choline. RT-PCR experiments demonstrated that the four genes encoding the Pot system are co-transcribed with murB, a gene involved in an intermediary step of peptidoglycan synthesis. Pneumococci grown in chemically-defined media (CDM) containing putrescine without choline enter logarithmic phase growth after 36-48 hs. However, culture density at stationary phase eventually reaches that of choline-containing medium. Cells grown in CDM-putrescine formed abnormally elongated chains in which the daughter cells failed to separate and the choline-binding protein PspA was no longer cell-associated. Experiments with CDM containing radiolabeled putrescine demonstrated that pneumococci concentrate this polyamine in cell walls. These data suggest that pneumococci can replicate without choline if putrescine is available and this polyamine may substitute for aminoalcohols in the cell wall teichoic acids.
Research Support, Non-U.S. Gov't
The Effect of Transformation on the Virulence of Streptococcus pneumoniae
Xue-Mei Zhang , Yi-Bing Yin , Dan Zhu , Bao-De Chen , Jin-Yong Luo , Yi-Ping Deng , Ming-Fang Liu , Shu-Hui Chen , Jiang-Ping Meng , Kai Lan , Yuan-Shuai Huang , Ge-Fei Kang
J. Microbiol. 2005;43(4):337-344.
DOI: https://doi.org/2256 [pii]
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AbstractAbstract PDF
Although pneumococcus is one of the most frequently encountered opportunistic pathogen in the world, the mechanisms responsible for its infectiveness have not yet been fully understood. In this paper, we have attempted to characterize the effects of pneumococcal transformation on the pathogenesis of the organism. We constructed three transformation-deficient pneumococcal strains, which were designated as Nos. 1d, 2d, and 22d. The construction of these altered strains was achieved via the insertion of the inactivated gene, comE, to strains 1, 2 and 22. We then conducted a comparison between the virulence of the transformation-deficient strains and that of the wild-type strains, via an evaluation of the ability of each strain to adhere to endothelial cells, and also assessed psaA mRNA expression, and the survival of hosts after bacterial challenge. Compared to what was observed with the wild-type strains, our results indicated that the ability of all of the transformation-deficient strains to adhere to the ECV304 cells had been significantly reduced (p < 0.05), the expression of psaA mRNA was reduced significantly (p < 0.05) in strains 2d and 22d, and the median survival time of mice infected with strains 1d and 2d was increased significantly after intraperitoneal bacterial challenge (p < 0.05). The results of our study also clearly indicated that transformation exerts significant effects on the virulence characteristics of S. pneumoniae, although the degree to which this effect is noted appears to depend primarily on the genetic background of the bacteria.
Optimization of culture conditions for production of pneumococcal capsular polysaccharide type I
Kim, Su Nam , Min, Kwan Ki , Kim, Seung Hwan , Choi, In Hwa , Lee, Suhk Hyung , Pyo, Suhk Noung , Rhee, Dong Kwon
J. Microbiol. 1996;34(2):179-183.
  • 207 View
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AbstractAbstract PDF
Streptoccus Pneumoniae (pneumococcus), the most common cause of bacterial pneumonia, has an ample polysaccharide (PS) capsule that is highly antigenic and is the source of PS vaccine. This investigation was undertaken to optimize the culture conditions for the production of capsulard PS by type 1 pneumococcus. Among several culture media, brain heart infusion (BHI) and Casitone based media were found to support luxuriant growth of pneumococcus type 1 at the same level. Because BHI medium is rather expensive and more complex than the Casitone based media, the Casitone based media was uwed to study optimization of the culture condition. The phase of growth which accomodated maximum PS production was logarithmic phase. Concentrations of glucose greater than 0.2% did not ehnahce growth or PS production. Substitution of netrogen sources with other resources or supplementation of various concentrations of metal ion (with the exception of calcium ion) had adverse affects on growth and PS production. On the other hand, low level aeration was beneficial for increased PS production. Addition of 3 mg/l concentration of methionine, phenylalanine, and threonine were found to enhance growth and PS production. The synerigistic effect of all the favorable conditions observed in pneumococcal growth assays provided a two-fold cummulative increase in capsular PS production.
Human Antibody Responses to Capsular Polysaccharides of Streptococcus pneumoniae 6B, 14, and 19F
Kim, Ji Hye , Kim, Kyung Hyo , Kim, Jung Soo , Song, Jae Ho , Park, Moon Kook
J. Microbiol. 1998;36(4):303-307.
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AbstractAbstract PDF
Human antibody responses to Streptococcus pneumoniae 6B, 14, and 19F capsular polysaccharide were analyzed. Thirty-one healthy young adults were immunized with the pneumococcal 23-valent PS vaccine. serum samples were obtained from them before and 1 month after vaccination. The amounts of total antibody, heavy chain and light chain isotypes were determined by enzyme-linked immunosorbent assay (ELISA). Vaccination increased the total lebvels of anti6B, anti-14, and anti-19F PS antibodies by 3.4-fold, 3.8-fold and 4.1-fold, respectively. Some inantibody was predominant in the responses to the three PSs, and most of the IgG anti-PS antibodies were IgG2 isotype. There was no significant difference in the k and λresponses.
Research Support, Non-U.S. Gov't
Detection of Enterovirus, Cytomegalovirus, and Chlamydia pneumoniae in Atheromas
Tae Won Kwon , Do Kyun Kim , Jeong Sook Ye , Won Joo Lee , Mi Sun Moon , Chul Hyun Joo , Heuiran Lee , Yoo Kyum Kim
J. Microbiol. 2004;42(4):299-304.
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AbstractAbstract PDF
To investigate the presence of infectious agents in human atherosclerotic arterial tissues. Atherosclerotic plaques were removed from 128 patients undergoing carotid endarterectomy or other bypass procedures for occlusive disease, and from twenty normal arterial wall samples, obtained from transplant donors with no history of diabetes, hypertension, smoking, or hyperlipidemia. Using the polymerase chain reaction (PCR) or reverse transcription-PCR, these samples were analyzed for the presence of Chlamydia pneumoniae, cytomegalovirus, enterovirus, adenovirus, herpes simplex viruses types 1 and 2, and Epstein-Barr virus. The amplicons were then sequenced, and phylogenetic analyses were performed. Enteroviral RNA was found in 22 of 128 atherosclerotic vascular lesions (17.2%), and C. pneumoniae and cytomegalovirus were each found in 2 samples (1.6%). In contrast, adenovirus, herpes simplex viruses, and Epstein-Barr virus were not identified in any of the atherosclerotic samples. Enterovirus was detected in 6/24 (25.0%) aortas, 7/33 (21.2%) carotid arteries, 6/40 (15.0%) femoral arteries, and 3/31 (9.7%) radial arteries of patients with chronic renal failure. There were no infectious agents detected in any of the control specimens. Using phylogenetic analysis, the enterovirus isolates were clustered into 3 groups, arranged as echovirus 9 and coxsackieviruses B1 and B3. Enteroviral RNA was detected in 17.2% of atherosclerotic plaques, but was not observed in any of the control specimens. This suggests a connection between enteroviral infection and atherosclerosis. These findings differ from those of other studies, which found more frequent incidence of C. pneumoniae and cytomegalovirus infection in atherosclerotic plaques.

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