Journal of Microbiology

Journal Article

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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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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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

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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Abstract

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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Functional and structural analyses of IMP-27 metallo-β-lactamase: evolution of IMP-type enzymes to overcome Zn(II) deprivation
Yoshiki Kato, Toshio Yamaguchi, Haruka Nakagawa-Kamura, Yoshikazu Ishii, Akiko Shimizu-Ibuka, Pablo Power
Microbiology Spectrum.2024;[Epub] CrossRef
Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors
Jessica L. Ortega-Balleza, Lenci K. Vázquez-Jiménez, Eyra Ortiz-Pérez, Guadalupe Avalos-Navarro, Alma D. Paz-González, Edgar E. Lara-Ramírez, Gildardo Rivera
Molecules.2024; 29(16): 3944. CrossRef
Understanding the Functional Dynamics of the TokK Enzyme in Carbapenem Biosynthesis via MD Simulations and QM/MM Calculations
Shakir Ali Siddiqui, Kshatresh Dutta Dubey
Inorganic Chemistry.2024; 63(40): 18963. CrossRef
Recent advances in functionalized macrocyclic polyamines for medicine applications
Hao Chang, Renzhong Qiao, Chao Li
Chinese Chemical Letters.2024; : 110675. CrossRef
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Ying Luo, Taha Majid Mahmood Sheikh, Xin Li, YuMeng Yuan, Fen Yao, Meimei Wang, Xiaoling Guo, Jilong Wu, Muhammad Shafiq, Qingdong Xie, Xiaoyang Jiao
Virulence.2024;[Epub] CrossRef
Decrypting biocontrol functions and application modes by genomes data of three Trichoderma Strains/Species
Shida Ji, Bin Liu, Jing Han, Ning Kong, Yongfeng Yang, Yucheng Wang, Zhihua Liu
Fungal Genetics and Biology.2024; 172: 103889. CrossRef
Revisiting the Checkerboard to Inform Development of β-Lactam/β-Lactamase Inhibitor Combinations
Darren J. Bentley
Antibiotics.2024; 13(4): 337. CrossRef
Role of β-Lactamase Inhibitors as Potentiators in Antimicrobial Chemotherapy Targeting Gram-Negative Bacteria
Song Zhang, Xinyu Liao, Tian Ding, Juhee Ahn
Antibiotics.2024; 13(3): 260. CrossRef
The C5α-Methyl-Substituted Carbapenem NA-1-157 Exhibits Potent Activity against Klebsiella spp. Isolates Producing OXA-48-Type Carbapenemases
Clyde A. Smith, Nichole K. Stewart, Marta Toth, Pojun Quan, John D. Buynak, Sergei B. Vakulenko
ACS Infectious Diseases.2023; 9(5): 1123. CrossRef
Phenotypes, genotypes and breakpoints: an assessment of β-lactam/β-lactamase inhibitor combinations against OXA-48
Tomefa E Asempa, Abigail K Kois, Christian M Gill, David P Nicolau
Journal of Antimicrobial Chemotherapy.2023; 78(3): 636. CrossRef
Characteristics of Extended-Spectrum β-Lactamase-Producing Escherichia coli Derived from Food and Humans in Northern Xinjiang, China
Yushuang Wu, Shudi Huang, Donglai Zhang, Hua Ji, Yongqing Ni, Xueling Zhang, Juan Dong, Baokun Li
Foodborne Pathogens and Disease.2023; 20(7): 270. CrossRef
Sequential C−H Methylation Catalyzed by the B12‐Dependent SAM Enzyme TokK: Comprehensive Theoretical Study of Selectivities
Wen‐Hao Deng, Rong‐Zhen Liao
Chemistry – A European Journal.2023;[Epub] CrossRef
CMOS Spectrophotometric Microsystem for Malaria Detection
Gabriel M. Ferreira, Vitória Baptista, Vítor Silva, Maria I. Veiga, Graça Minas, Susana O. Catarino
IEEE Transactions on Biomedical Engineering.2023; 70(8): 2318. CrossRef
Synthesis and β-Lactamase Inhibition Activity of Imidates of Diazabicyclooctane
Lijuan Zhai, Jian Sun, Jingwen Ji, Lili He, Yuanyu Gao, Jinbo Ji, Yuanbai Liu, Yangxiu Mu, Xueqin Ma, Dong Tang, Haikang Yang, Zafar Iqbal, Zhixiang Yang
Russian Journal of Bioorganic Chemistry.2022; 48(5): 1059. CrossRef
Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
Zafar Iqbal, Jian Sun, Haikang Yang, Jingwen Ji, Lili He, Lijuan Zhai, Jinbo Ji, Pengjuan Zhou, Dong Tang, Yangxiu Mu, Lin Wang, Zhixiang Yang
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Retracted and replaced: Phenotypes, genotypes and breakpoints: an assessment of β-lactam/ β-lactamase inhibitor combinations against OXA-48
Tomefa E Asempa, Abigail K Kois, Christian M Gill, David P Nicolau
Journal of Antimicrobial Chemotherapy.2022; 77(10): 2622. CrossRef
Carbapenemase producing Klebsiella pneumoniae: implication on future therapeutic strategies
Ilias Karaiskos, Irene Galani, Vassiliki Papoutsaki, Lamprini Galani, Helen Giamarellou
Expert Review of Anti-infective Therapy.2022; 20(1): 53. CrossRef
Antimicrobial Activity of Dihydroisocoumarin Isolated from Wadi Lajab Sediment-Derived Fungus Penicillium chrysogenum: In Vitro and In Silico Study
Raha Orfali, Shagufta Perveen, Mohamed Fahad AlAjmI, Safina Ghaffar, Md Tabish Rehman, Abdullah R. AlanzI, Saja Bane Gamea, Mona Essa Khwayri
Molecules.2022; 27(11): 3630. CrossRef
The Odd Couple(s): An Overview of Beta-Lactam Antibiotics Bearing More Than One Pharmacophoric Group
Margherita De Rosa, Anna Verdino, Annunziata Soriente, Anna Marabotti
International Journal of Molecular Sciences.2021; 22(2): 617. CrossRef
Drugs That Changed Society: History and Current Status of the Early Antibiotics: Salvarsan, Sulfonamides, and β-Lactams
Søren Brøgger Christensen
Molecules.2021; 26(19): 6057. CrossRef
In Crystallo Time-Resolved Interaction of the Clostridioides difficile CDD-1 enzyme with Avibactam Provides New Insights into the Catalytic Mechanism of Class D β-lactamases
Nichole K. Stewart, Marta Toth, Anastasiya Stasyuk, Sergei B. Vakulenko, Clyde A. Smith
ACS Infectious Diseases.2021; 7(6): 1765. CrossRef
Inhibition of the Clostridioides difficile Class D β-Lactamase CDD-1 by Avibactam
Nichole K. Stewart, Marta Toth, Anastasiya Stasyuk, Mijoon Lee, Clyde A. Smith, Sergei B. Vakulenko
ACS Infectious Diseases.2021; 7(5): 1164. CrossRef

Journal Articles

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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Abstract

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.

Citations

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Maternal immune activation mediated prenatal chronic stress induces Th17/Treg cell imbalance may relate to the PI3K/Akt/NF-κB signaling pathway in offspring rats
Ye Li, Guixiang Yao, Rui Wang, Jiashu Zhu, Hongyu Li, Deguang Yang, Shuqin Ma, Youjuan Fu, Can Liu, Suzhen Guan
International Immunopharmacology.2024; 126: 111308. CrossRef
Secreted protein NFA47630 from Nocardia farcinica IFM10152 induces immunoprotective effects in mice
Lichao Han, Xingzhao Ji, Shihong Fan, Jirao Shen, Bin Liang, Zhenjun Li
Tropical Diseases, Travel Medicine and Vaccines.2024;[Epub] CrossRef
Human microbiomes in cancer development and therapy
Chenglai Xia, Jiyan Su, Can Liu, Zhikai Mai, Shuanghong Yin, Chuansheng Yang, Liwu Fu
MedComm.2023;[Epub] CrossRef
Identification and Analysis of Potential Immune-Related Biomarkers in Endometriosis
Yanan He, Jixin Li, Yanjun Qu, Liyuan Sun, Xibo Zhao, Han Wu, Guangmei Zhang, Amar Singh
Journal of Immunology Research.2023; 2023: 1. CrossRef
The identification of two M20B family peptidases required for full virulence in Staphylococcus aureus
Nathanial J. Torres, Devon N. Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey N. Shaw
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
Exploration of immune response mechanisms in cadmium and copper co-exposed juvenile golden cuttlefish (Sepia esculenta) based on transcriptome profiling
Xiaokai Bao, Weijun Wang, Xipan Chen, Yanwei Feng, Xiaohui Xu, Guohua Sun, Bin Li, Xiumei Liu, Zan Li, Jianmin Yang
Frontiers in Immunology.2022;[Epub] CrossRef
Pathogenicity and virulence ofStreptococcus pneumoniae: Cutting to the chase on proteases
Mary E. Marquart
Virulence.2021; 12(1): 766. CrossRef
Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics
Chang Yi Shi, Chen Huan Yu, Wen Ying Yu, Hua Zhong Ying, Hua Zhang
Canadian Journal of Infectious Diseases and Medical Microbiology.2021; 2021: 1. CrossRef

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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Abstract

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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Acute otitis media pneumococcal disease burden and nasopharyngeal colonization in children due to serotypes included and not included in current and new pneumococcal conjugate vaccines
Michael Pichichero, Richard Malley, Ravinder Kaur, Robert Zagursky, Porter Anderson
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Yuyu Wang, Jianjiang Huang, Fang Zhang, Keli Shen, Bin Qiu
Growth Factors.2023; 41(4): 210. CrossRef
Occurrence of influenza and bacterial infections in cancer patients receiving radiotherapy in Ghana
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,
PLOS ONE.2022; 17(7): e0271877. CrossRef
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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William Walkowski, Justin Bassett, Manmeet Bhalla, Blaine A. Pfeifer, Elsa N. Bou Ghanem
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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
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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
Scientific Reports.2020;[Epub] CrossRef
Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection
Catherine B. Blackwood, Emel Sen-Kilic, Dylan T. Boehm, Jesse M. Hall, Melinda E. Varney, Ting Y. Wong, Shelby D. Bradford, Justin R. Bevere, William T. Witt, F. Heath Damron, Mariette Barbier
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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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Victor Morais, Esther Texeira, Norma Suarez
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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

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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Abstract

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
Nature Communications.2017;[Epub] CrossRef
New chemical tools to probe cell wall biosynthesis in bacteria
Robert T Gale, Eric D Brown
Current Opinion in Microbiology.2015; 27: 69. CrossRef

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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Abstract

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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Streptococcus pneumoniae serotype distribution in low- and middle-income countries of South Asia: Do we need to revisit the pneumococcal vaccine strategy?
Priya Dhawale, Sanket Shah, Kaushal Sharma, Deepa Sikriwal, Varnik Kumar, Arnabjyoti Bhagawati, Sakshi Dhar, Pratiksha Shetty, Syed Ahmed
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Ayesha Zahid, Jennifer C. Wilson, I. Darren Grice, Ian R. Peak
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Corrected and Republished from: “A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge”
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Infection and Immunity.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
Pneumococcal Choline-Binding Proteins Involved in Virulence as Vaccine Candidates
Julio Sempere, Mirella Llamosí, Idoia del Río Menéndez, Beatriz López Ruiz, Mirian Domenech, Fernando González-Camacho
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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
Novel Protein-Based Pneumococcal Vaccines: Assessing the Use of Distinct Protein Fragments Instead of Full-Length Proteins as Vaccine Antigens
Theano Lagousi, Paraskevi Basdeki, John Routsias, Vana Spoulou
Vaccines.2019; 7(1): 9. CrossRef
A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge
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
Infection and Immunity.2019;[Epub] CrossRef
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Mona Mohammadzadeh, Babak Pourakbari, Shima Mahmoudi, Abbas Keshtkar, Mahdi Habibi-Anbouhi, Setareh Mamishi
Microbial Pathogenesis.2018; 122: 122. CrossRef
Construction and evaluation of a whole-cell pneumococcal vaccine candidate
M. Mohammadzadeh, B. Pourakbari, A. Doosti, S. Mahmoudi, M. Habibi-Anbouhi, S. Mamishi
Journal of Applied Microbiology.2018; 125(6): 1901. CrossRef
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
Journal of Microbiology.2017; 55(10): 823. CrossRef
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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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Abstract

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.

Citations

Citations to this article as recorded by

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Irene Jiménez-Munguía, Mónica Calderón-Santiago, Antonio Rodríguez-Franco, Feliciano Priego-Capote, Manuel J. Rodríguez-Ortega
PeerJ.2018; 6: e4966. CrossRef
Mycoplasma fermentans deacetylase promotes mammalian cell stress tolerance
Qingzhou Cheng, Lijuan Wu, Rongfu Tu, Jun Wu, Wenqian Kang, Tong Su, Runlei Du, Wenbin Liu
Microbiological Research.2017; 201: 1. CrossRef
Serotype IV Sequence Type 468 Group BStreptococcusNeonatal Invasive Disease, Minnesota, USA
Sarah Teatero, Patricia Ferrieri, Nahuel Fittipaldi
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Mass Spectrometry in Clinical Microbiology and Infectious Diseases
Frank Fleurbaaij, Hans C. van Leeuwen, Oleg I. Klychnikov, Ed J. Kuijper, Paul J. Hensbergen
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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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Abstract: 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.

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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Abstract: 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.

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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Abstract: 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.

Journal Article

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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Abstract: 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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Abstract: 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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Abstract: 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.

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Abstract: 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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Abstract: 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.

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