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Membrane Proteins as a Regulator for Antibiotic Persistence in Gram‑Negative Bacteria
Jia Xin Yee , Juhyun Kim , Jinki Yeom
J. Microbiol. 2023;61(3):331-341.   Published online February 17, 2023
DOI: https://doi.org/10.1007/s12275-023-00024-w
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  • 4 Web of Science
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AbstractAbstract PDF
Antibiotic treatment failure threatens our ability to control bacterial infections that can cause chronic diseases. Persister bacteria are a subpopulation of physiological variants that becomes highly tolerant to antibiotics. Membrane proteins play crucial roles in all living organisms to regulate cellular physiology. Although a diverse membrane component involved in persistence can result in antibiotic treatment failure, the regulations of antibiotic persistence by membrane proteins has not been fully understood. In this review, we summarize the recent advances in our understanding with regards to membrane proteins in Gram-negative bacteria as a regulator for antibiotic persistence, highlighting various physiological mechanisms in bacteria.

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  • Cardamom essential oil-loaded zinc oxide nanoparticles: A sustainable antimicrobial strategy against multidrug-resistant foodborne pathogens
    Mabrouk Sobhy, Tamer Elsamahy, Esraa A. Abdelkarim, Ebtihal Khojah, Haiying Cui, Lin Lin
    Microbial Pathogenesis.2025; 205: 107661.     CrossRef
  • Amino Acid and Au(III) Self-Assembled Supramolecular Nanozymes for Antimicrobial Applications
    Yunzhu Xu, Dahai Hou, Min Zhao, Tong Zhao, Yong Ma, Yafeng Zhang, Yang Guo, Weiwei Tao, Hui Wang
    ACS Applied Nano Materials.2024; 7(19): 22505.     CrossRef
  • PhoPQ-mediated lipopolysaccharide modification governs intrinsic resistance to tetracycline and glycylcycline antibiotics in Escherichia coli
    Byoung Jun Choi, Umji Choi, Dae-Beom Ryu, Chang-Ro Lee, Mehrad Hamidian, You-Hee Cho
    mSystems.2024;[Epub]     CrossRef
  • Bacterial Regulatory Mechanisms for the Control of Cellular Processes: Simple Organisms’ Complex Regulation
    Jin-Won Lee
    Journal of Microbiology.2023; 61(3): 273.     CrossRef
Journal Articles
Mutational analysis on stable expression and LasB inhibition of LasB propeptide in Pseudomonas aeruginosa
Youngsun Shin , Xi-Hui Li , Cheol Seung Lee , Joon-Hee Lee
J. Microbiol. 2022;60(7):727-734.   Published online May 25, 2022
DOI: https://doi.org/10.1007/s12275-022-1671-5
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AbstractAbstract PDF
Three major proteases, elastase B (LasB), protease IV (PIV), and elastase A (LasA) expressed in Pseudomonas aeruginosa play important roles in infections and pathogeneses. These are activated by a proteolytic cascade initiated by the activation of LasB. In this study, we investigated whether LasB could be inhibited using its propeptide (LasBpp). Although LasA and PIV were inhibited by their propeptides, LasB was not inhibited by purified LasBpp because LasB degraded LasBpp. To address this problem, mutant LasBpp variants were constructed to obtain a mutant LasBpp resistant to LasB degradation. A C-terminal deletion series of LasBpp was tested in vivo, and two positive candidates, T2 and T2-1, were selected. However, both caused growth retardation and were unstably expressed in vivo. Since deleting the C-terminal end of LasBpp significantly affected its stable expression, substitution mutations were introduced at the two amino acids near the truncation site of T2-1. The resulting mutants, LasBppE172D, LasBppG173A, and LasBppE172DG173A, significantly diminished LasB activity when overexpressed in vivo and were stably expressed in MW1, a quorum sensing mutant that does not produce LasB. In vitro analysis showed that purified LasBppE172DG173A inhibited LasB activity to a small extent. Summarizing, Cterminal modification of LasBpp profoundly affected the stable expression of LasBpp, and little enhanced the ability of LasBpp to resist degradation by LasB.

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  • LasB activation in Pseudomonas aeruginosa: Quorum sensing-mediated release of an auto-activation inhibitor
    Cheol Seung Lee, Xi-Hui Li, Chae-Ran Jeon, Joon-Hee Lee
    Journal of Microbiology.2025; 63(2): e2411005.     CrossRef
Lactobacillus plantarum-derived metabolites sensitize the tumorsuppressive effects of butyrate by regulating the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells
Hye-Ju Kim , JaeJin An , Eun-Mi Ha
J. Microbiol. 2022;60(1):100-117.   Published online December 29, 2021
DOI: https://doi.org/10.1007/s12275-022-1533-1
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  • 32 Web of Science
  • 28 Crossref
AbstractAbstract PDF
A critical obstacle to the successful treatment of colorectal cancer (CRC) is chemoresistance. Chemoresistant CRC cells contribute to treatment failure by providing a mechanism of drug lethargy and modifying chemoresistance-associated molecules. The gut microbiota provide prophylactic and therapeutic effects by targeting CRC through anticancer mechanisms. Among them, Lactobacillus plantarum contributes to the health of the host and is clinically effective in treating CRC. This study confirmed that 5-fluorouracil (5-FU)-resistant CRC HCT116 (HCT116/5FUR) cells acquired butyrateinsensitive properties. To date, the relationship between 5- FU-resistant CRC and butyrate resistance has not been elucidated. Here, we demonstrated that the acquisition of butyrate resistance in HCT116/5FUR cells was strongly correlated with the inhibition of the expression and function of SMCT1, a major transporter of butyrate in colonocytes. L. plantarum-cultured cell-free supernatant (LP) restored the functional expression of SMCT1 in HCT116/5FUR cells, leading to butyrate-induced antiproliferative effect and apoptosis. These results suggest that LP has a synergistic effect on the SMCT1/butyrate-mediated tumor suppressor function and is a potential chemosensitizer to overcome dual 5-FU and butyrate resistance in HCT116 cells.

Citations

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  • Advancements in the Pathogenesis, Diagnosis, and Therapeutic Implications of Intestinal Bacteria
    Duofei Lu, Xianxiong Ma, Kaixiong Tao, Hongwei Lei
    Current Issues in Molecular Biology.2025; 47(2): 106.     CrossRef
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    Joshua Tobias, Stefan Heinl, Kristina Dendinovic, Ajša Ramić, Anna Schmid, Catherine Daniel, Ursula Wiedermann
    Immunology Letters.2025; 272: 106971.     CrossRef
  • Advances in understanding therapeutic mechanisms of probiotics in cancer management, with special emphasis on breast cancer: A comprehensive review
    A S Angel Nama, G Mary Sandeepa, Viswanath Buddolla, Anthati Mastan
    European Journal of Pharmacology.2025; 995: 177410.     CrossRef
  • Unlocking the power of probiotics, postbiotics: targeting apoptosis for the treatment and prevention of digestive diseases
    Qiuyan Xie, Ji Liu, Ping Yu, Ting Qiu, Shanyu Jiang, Renqiang Yu
    Frontiers in Nutrition.2025;[Epub]     CrossRef
  • Unveiling the Interplay Between the Human Microbiome and Gastric Cancer: A Review of the Complex Relationships and Therapeutic Avenues
    Jenan Al-Matouq, Hawra Al-Ghafli, Noura N. Alibrahim, Nida Alsaffar, Zaheda Radwan, Mohammad Daud Ali
    Cancers.2025; 17(2): 226.     CrossRef
  • The role of gut microbiota and metabolites in cancer chemotherapy
    Shiyu Li, Shuangli Zhu, Jun Yu
    Journal of Advanced Research.2024; 64: 223.     CrossRef
  • Sodium Butyrate Inhibits the Expression of Thymidylate Synthase and Induces Cell Death in Colorectal Cancer Cells
    Nayeon Kim, Changwon Yang
    International Journal of Molecular Sciences.2024; 25(3): 1572.     CrossRef
  • Anticancer Properties of Saccharomyces boulardii Metabolite Against Colon Cancer Cells
    Babak Pakbin, Samaneh Allahyari, Shaghayegh Pishkhan Dibazar, Amir Peymani, Mozhdeh Khajeh Haghverdi, Khadijeh Taherkhani, Maryam Javadi, Razzagh Mahmoudi
    Probiotics and Antimicrobial Proteins.2024; 16(1): 224.     CrossRef
  • The effect of oral butyrate on colonic short-chain fatty acid transporters and receptors depends on microbial status
    Karla Vagnerová, Tomáš Hudcovic, Martin Vodička, Peter Ergang, Petra Klusoňová, Petra Petr Hermanová, Dagmar Šrůtková, Jiří Pácha
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Exploiting lactic acid bacteria for colorectal cancer: a recent update
    Yang Chen, Bo Yang, Jianxin Zhao, R. Paul Ross, Catherine Stanton, Hao Zhang, Wei Chen
    Critical Reviews in Food Science and Nutrition.2024; 64(16): 5433.     CrossRef
  • Gut microbial metabolites: Shaping future diagnosis and treatment against gastrointestinal cancer
    Hongyan Gou, Ruijie Zeng, Harry Cheuk Hay Lau, Jun Yu
    Pharmacological Research.2024; 208: 107373.     CrossRef
  • Probiotics intervention in colorectal cancer: From traditional approaches to novel strategies
    Suki Ha, Xiang Zhang, Jun Yu
    Chinese Medical Journal.2024; 137(1): 8.     CrossRef
  • A Narrative Review on the Advance of Probiotics to Metabiotics
    Hye Ji Jang, Na-Kyoung Lee, Hyun-Dong Paik
    Journal of Microbiology and Biotechnology.2024; 34(3): 487.     CrossRef
  • Pharmacomicrobiomics of cell-cycle specific anti-cancer drugs – is it a new perspective for personalized treatment of cancer patients?
    Karolina Kaźmierczak-Siedlecka, Nikola Bulman, Paweł Ulasiński, Bartosz Kamil Sobocki, Karol Połom, Luigi Marano, Leszek Kalinowski, Karolina Skonieczna-Żydecka
    Gut Microbes.2023;[Epub]     CrossRef
  • Participation of protein metabolism in cancer progression and its potential targeting for the management of cancer
    Dalong Liu, Yun Wang, Xiaojiang Li, Yan Wang, Zhiqiang Zhang, Zhifeng Wang, Xudong Zhang
    Amino Acids.2023; 55(10): 1223.     CrossRef
  • Microbial metabolites in colorectal tumorigenesis and cancer therapy
    Yali Liu, Harry Cheuk-Hay Lau, Jun Yu
    Gut Microbes.2023;[Epub]     CrossRef
  • Lactobacillus plantarum Metabolites Elicit Anticancer Effects by Inhibiting Autophagy-Related Responses
    Sihyun Jeong, Yuju Kim, Soyeong Park, Doyeon Lee, Juho Lee, Shwe Phyu Hlaing, Jin-Wook Yoo, Sang Hoon Rhee, Eunok Im
    Molecules.2023; 28(4): 1890.     CrossRef
  • Lactobacillus plantarum modulate gut microbiota and intestinal immunity in cyclophosphamide-treated mice model
    Zhibo Zeng, Zonghao Huang, Wen Yue, Shah Nawaz, Xinzhu Chen, Jing Liu
    Biomedicine & Pharmacotherapy.2023; 169: 115812.     CrossRef
  • Gut Microbiome in Colorectal Cancer: Clinical Diagnosis and Treatment
    Yali Liu, Harry Cheuk-Hay Lau, Wing Yin Cheng, Jun Yu
    Genomics, Proteomics & Bioinformatics.2023; 21(1): 84.     CrossRef
  • Research progress of traditional Chinese medicine as sensitizer in reversing chemoresistance of colorectal cancer
    Xiang Lin, Xinyu Yang, Yushang Yang, Hangbin Zhang, Xuan Huang
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Characterization of Wnt signaling pathway under treatment of Lactobacillus acidophilus postbiotic in colorectal cancer using an integrated in silico and in vitro analysis
    Nafiseh Erfanian, Saeed Nasseri, Adib Miraki Feriz, Hossein Safarpour, Mohammad Hassan Namaei
    Scientific Reports.2023;[Epub]     CrossRef
  • A Review of Gut Microbiota‐Derived Metabolites in Tumor Progression and Cancer Therapy
    Qiqing Yang, Bin Wang, Qinghui Zheng, Heyu Li, Xuli Meng, Fangfang Zhou, Long Zhang
    Advanced Science.2023;[Epub]     CrossRef
  • Anti-tumour effect of Huangqin Decoction on colorectal cancer mice through microbial butyrate mediated PI3K/Akt pathway suppression
    Jia-Jie Zhu, Hai-Yan Liu, Liang-Jun Yang, Zheng Fang, Rui Fu, Jia-Bin Chen, Shan Liu, Bao-Ying Fei
    Journal of Medical Microbiology .2023;[Epub]     CrossRef
  • Fecal levels of SCFA and BCFA during capecitabine in patients with metastatic or unresectable colorectal cancer
    Janine Ziemons, Romy Aarnoutse, Anne Heuft, Lars Hillege, Janneke Waelen, Judith de Vos-Geelen, Liselot Valkenburg-van Iersel, Irene E. G. van Hellemond, Geert-Jan M. Creemers, Arnold Baars, Johanna H. M. J. Vestjens, John Penders, Koen Venema, Marjolein
    Clinical and Experimental Medicine.2023; 23(7): 3919.     CrossRef
  • Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment
    Christina Thoda, Maria Touraki
    Microorganisms.2023; 11(8): 1898.     CrossRef
  • Gut microbiota and microbiota-derived metabolites in colorectal cancer: enemy or friend
    Xinyi Wang, Xicai Sun, Jinjin Chu, Wenchang Sun, Shushan Yan, Yaowen Wang
    World Journal of Microbiology and Biotechnology.2023;[Epub]     CrossRef
  • Determination of the effect of L. plantarum AB6-25, L. plantarum MK55 and S. boulardii T8-3C microorganisms on colon, cervix, and breast cancer cell lines: Molecular docking, and molecular dynamics study
    Seda Yalçınkaya, Serap Yalçın Azarkan, Aynur Gül Karahan Çakmakçı
    Journal of Molecular Structure.2022; 1261: 132939.     CrossRef
  • Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells
    JaeJin An, Eun-Mi Ha
    Journal of Microbiology.2022; 60(7): 735.     CrossRef
Short-chain fatty acids inhibit the biofilm formation of Streptococcus gordonii through negative regulation of competence-stimulating peptide signaling pathway
Taehwan Park , Jintaek Im , A Reum Kim , Dongwook Lee , Sungho Jeong , Cheol-Heui Yun , Seung Hyun Han
J. Microbiol. 2021;59(12):1142-1149.   Published online December 4, 2021
DOI: https://doi.org/10.1007/s12275-021-1576-8
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AbstractAbstract PDF
Streptococcus gordonii, a Gram-positive commensal bacterium, is an opportunistic pathogen closely related to initiation and progression of various oral diseases, such as periodontitis and dental caries. Its biofilm formation is linked with the development of such diseases by enhanced resistance against antimicrobial treatment or host immunity. In the present study, we investigated the effect of short-chain fatty acids (SCFAs) on the biofilm formation of S. gordonii. SCFAs, including sodium acetate (NaA), sodium propionate (NaP), and sodium butyrate (NaB), showed an effective inhibitory activity on the biofilm formation of S. gordonii without reduction in bacterial growth. SCFAs suppressed S. gordonii biofilm formation at early time points whereas SCFAs did not affect its preformed biofilm. A quorum-sensing system mediated by competence-stimulating peptide (CSP) is known to regulate biofilm formation of streptococci. Interestingly, SCFAs substantially decreased mRNA expression of comD and comE, which are CSP-sensor and its response regulator responsible for CSP pathway, respectively. Although S. gordonii biofilm formation was enhanced by exogenous synthetic CSP treatment, such effect was not observed in the presence of SCFAs. Collectively, these results suggest that SCFAs have an anti-biofilm activity on S. gordonii through inhibiting comD and comE expression which results in negative regulation of CSP quorum-sensing system. SCFAs could be an effective anti-biofilm agent against S. gordonii for the prevention of oral diseases.

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    María José Mendoza-León, Ashutosh K. Mangalam, Alejandro Regaldiz, Enrique González-Madrid, Ma. Andreina Rangel-Ramírez, Oscar Álvarez-Mardonez, Omar P. Vallejos, Constanza Méndez, Susan M. Bueno, Felipe Melo-González, Yorley Duarte, Ma. Cecilia Opazo, Al
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    Richard J. Lamont, George Hajishengallis, Hyun Koo, Anthony R. Richardson
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[PROTOCOL] Flow cytometric monitoring of the bacterial phenotypic diversity in aquatic ecosystems
Jin-Kyung Hong , Soo Bin Kim , Seok Hyun Ahn , Yongjoo Choi , Tae Kwon Lee
J. Microbiol. 2021;59(10):879-885.   Published online September 23, 2021
DOI: https://doi.org/10.1007/s12275-021-1443-7
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AbstractAbstract PDF
Flow cytometry is a promising tool used to identify the phenotypic features of bacterial communities in aquatic ecosystems by measuring the physical and chemical properties of cells based on their light scattering behavior and fluorescence. Compared to molecular or culture-based approaches, flow cytometry is suitable for the online monitoring of microbial water quality because of its relatively simple sample preparation process, rapid analysis time, and high-resolution phenotypic data. Advanced statistical techniques (e.g., denoising and binning) can be utilized to successfully calculate phenotypic diversity by processing the scatter data obtained from flow cytometry. These phenotypic diversities were well correlated with taxonomic-based diversity computed using nextgeneration 16S RNA gene sequencing. The protocol provided in this paper should be a useful guide for a fast and reliable flow cytometric monitoring of bacterial phenotypic diversity in aquatic ecosystems.

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  • Enhancing Bacterial Phenotype Classification Through the Integration of Autogating and Automated Machine Learning in Flow Cytometric Analysis
    In Jae Jeong, Jin‐Kyung Hong, Young Jun Bae, Tea Kwon Lee
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  • Assessing long-term ecological impacts of PCE contamination in groundwater using a flow cytometric fingerprint approach
    Jin-Kyung Hong, Soo Bin Kim, Gui Nam Wee, Bo Ram Kang, Jee Hyun No, Susmita Das Nishu, Joonhong Park, Tae Kwon Lee
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    Gui Nam Wee, Eun Sun Lyou, Susmita Das Nishu, Tae Kwon Lee
    Frontiers in Microbiology.2023;[Epub]     CrossRef
Full-repertoire comparison of the microscopic objects composing the human gut microbiome with sequenced and cultured communities
Edmond Kuete Yimagou , Jean-Pierre Baudoin , Rita Abou Abdallah , Fabrizio Di Pinto , Jacques Yaacoub Bou Khalil , Didier Raoult
J. Microbiol. 2020;58(5):377-386.   Published online April 11, 2020
DOI: https://doi.org/10.1007/s12275-020-9365-3
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AbstractAbstract PDF
The study of the human gut microbiome is essential in microbiology and infectious diseases as specific alterations in the gut microbiome might be associated with various pathologies, such as chronic inflammatory disease, intestinal infection and colorectal cancer. To identify such dysregulations, several strategies are being used to create a repertoire of the microorganisms composing the human gut microbiome. In this study, we used the “microscomics” approach, which consists of creating an ultrastructural repertoire of all the cell-like objects composing stool samples from healthy donors using transmission electron microscopy (TEM). We used TEM to screen ultrathin sections of 8 resin-embedded stool samples. After exploring hundreds of micrographs, we managed to elaborate ultrastructural categories based on morphological criteria or features. This approach explained many inconsistencies observed with other techniques, such as metagenomics and culturomics. We highlighted the value of our cultureindependent approach by comparing our microscopic images to those of cultured bacteria and those reported in the literature. This study helped to detect “minimicrobes” Candidate Phyla Radiation (CPR) for the first time in human stool samples. This “microscomics” approach is non-exhaustive but complements already existing approaches and adds important data to the puzzle of the microbiota.

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Differential expression of the major catalase, KatA in the two wild type Pseudomonas aeruginosa strains, PAO1 and PA14
Bi-o Kim , In-Young Chung , You-Hee Cho
J. Microbiol. 2019;57(8):704-710.   Published online June 11, 2019
DOI: https://doi.org/10.1007/s12275-019-9225-1
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AbstractAbstract PDF
KatA is the major catalase required for hydrogen peroxide (H2O2) resistance and acute virulence in Pseudomonas aeruginosa PA14, whose transcription is governed by its dual promoters (katAp1 and katAp2). Here, we observed that KatA was not required for acute virulence in another wild type P. aeruginosa strain, PAO1, but that PAO1 exhibited higher KatA expression than PA14 did. This was in a good agreement with the observation that PAO1 was more resistant than PA14 to H2O2 as well as to the antibiotic peptide, polymyxin B (PMB), supposed to involve reactive oxygen species (ROS) for its antibacterial activity. The higher KatA expression in PAO1 than in PA14 was attributed to both katAp1 and katAp2 transcripts, as assessed by S1 nuclease mapping. In addition, it was confirmed that the PMB resistance is attributed to both katAp1 and katAp2 in a complementary manner in PA14 and PAO1, by exploiting the promoter mutants for each -10 box (p1m, p2m, and p1p2m). These results provide an evidence that the two widely used P. aeruginosa strains display different virulence mechanisms associated with OxyR and Anr, which need to be further characterized for better understanding of the critical virulence pathways that may differ in various P. aeruginosa strains.

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Low-density lipoprotein as an opsonin promoting the phagocytosis of Pseudomonas aeruginosa by U937 cells
Yuxin Li , Zhi Liu , Jinli Yang , Ling Liu , Runlin Han
J. Microbiol. 2019;57(8):711-716.   Published online May 11, 2019
DOI: https://doi.org/10.1007/s12275-019-8413-3
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AbstractAbstract PDF
Low-density lipoprotein (LDL) was recently reported to be an opsonin, enhancing the phagocytosis of group A Streptococcus (GAS) by human monocytic leukemia U937 cells due to the binding of LDL to some GAS strains. We postulated that LDL might also promote the opsonophagocytosis of Pseudomonas aeruginosa by U937 cells since this bacterium interacts with LDL. In this study, P. aeruginosa (CMCC10104), U937 cells, and human LDL were used in phagocytosis assays to test our hypothesis. Escherichia coli strain BL21, which does not interact with LDL, was used as a negative control. Colony counting and fluorescence microscopy were used to determine the bacterial quantity in the opsonophagocytosis assays. After incubation of U937 cells and P. aeruginosa with LDL (100 μg/ml) for 15 and 30 min, phagocytosis was observed to be increased by 22.71% and 32.90%, respectively, compared to that seen in the LDL-free group. However, LDL did not increase the phagocytosis of E. coli by U937 cells. In addition, we identified CD36 as a major opsonin receptor on U937 cells, since an anti-CD36 monoclonal antibody, but not an anti- CD4 monoclonal antibody, almost completely abolished the opsonophagocytosis of P. aeruginosa by U937 cells.

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  • Adhesion of Enteropathogenic, Enterotoxigenic, and Commensal Escherichia coli to the Major Zymogen Granule Membrane Glycoprotein 2
    Christin Bartlitz, Rafał Kolenda, Jarosław Chilimoniuk, Krzysztof Grzymajło, Stefan Rödiger, Rolf Bauerfeind, Aamir Ali, Veronika Tchesnokova, Dirk Roggenbuck, Peter Schierack, Isaac Cann
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    Zhi Liu, Yuxin Li, Yu Wang, Zhe Liu, Yan Su, Qiang Ma, Runlin Han, Enrique Ortega
    Journal of Immunology Research.2021; 2021: 1.     CrossRef
Antibiofilm effect of biofilm-dispersing agents on clinical isolates of Pseudomonas aeruginosa with various biofilm structures
Soo-Kyoung Kim , Xi-Hui Li , Hyeon-Ji Hwang , Joon-Hee Lee
J. Microbiol. 2018;56(12):902-909.   Published online October 25, 2018
DOI: https://doi.org/10.1007/s12275-018-8336-4
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AbstractAbstract PDF
Pseudomonas aeruginosa, an opportunistic human pathogen, causes many biofilm-mediated chronic infections. In this study, biofilm structures of various clinical strains of P. aeruginosa isolated from hospitalized patients were examined and their influence on the biofilm-dispersing effects of chemicals was investigated. The clinical isolates formed structurally distinct biofilms that could be classified into three different groups: 1) mushroom-like, 2) thin flat, and 3) thick flat structures. A dispersion of these differently structured biofilms was induced using two biofilm-dispersing agents, anthranilate and sodium nitroprusside (SNP). Although both SNP and anthranilate could disperse all types of biofilms, the thick flat biofilms were dispersed less efficiently than the biofilms of other structures. This suggests that biofilm-dispersing agents have higher potency on the biofilms of porous structures than on densely packed biofilms.

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[PROTOCOL] Drosophila melanogaster as a polymicrobial infection model for Pseudomonas aeruginosa and Staphylococcus aureus
Young-Joon Lee , Hye-Jeong Jang , In-Young Chung , You-Hee Cho
J. Microbiol. 2018;56(8):534-541.   Published online July 25, 2018
DOI: https://doi.org/10.1007/s12275-018-8331-9
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AbstractAbstract PDF
Non-mammalian infection models have been developed over the last two decades, which is a historic milestone to understand the molecular basis of bacterial pathogenesis. They also provide small-scale research platforms for identification of virulence factors, screening for antibacterial hits, and evaluation of antibacterial efficacy. The fruit fly, Drosophila melanogaster is one of the model hosts for a variety of bacterial pathogens, in that the innate immunity pathways and tissue physiology are highly similar to those in mammals. We here present a relatively simple protocol to assess the key aspects of the polymicrobial interaction in vivo between the human opportunistic pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, which is based on the systemic infection by needle pricking at the dorsal thorax of the flies. After infection, fly survival and bacteremia over time for both P. aeruginosa and S. aureus within the infected flies can be monitored as a measure of polymicrobial virulence potential. The infection takes ~24 h including bacterial cultivation. Fly survival and bacteremia are assessed using the infected flies that are monitored up to ~60 h post-infection. These methods can be used to identify presumable as well as unexpected phenotypes during polymicrobial interaction between P. aeruginosa and S. aureus mutants, regarding bacterial pathogenesis and host immunity.

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Review
[MINIREVIEW] Interdependence between iron acquisition and biofilm formation in Pseudomonas aeruginosa
Donghoon Kang , Natalia V. Kirienko
J. Microbiol. 2018;56(7):449-457.   Published online June 14, 2018
DOI: https://doi.org/10.1007/s12275-018-8114-3
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AbstractAbstract PDF
Bacterial biofilms remain a persistent threat to human healthcare due to their role in the development of antimicrobial resistance. To combat multi-drug resistant pathogens, it is crucial to enhance our understanding of not only the regulation of biofilm formation, but also its contribution to bacterial virulence. Iron acquisition lies at the crux of these two subjects. In this review, we discuss the role of iron acquisition in biofilm formation and how hosts impede this mechanism to defend against pathogens. We also discuss recent findings that suggest that biofilm formation can also have the reciprocal effect, influencing siderophore production and iron sequestration.

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Journal Articles
A common evolutionary pathway for maintaining quorum sensing in Pseudomonas aeruginosa
Bai-min Lai , Hui-cong Yan , Mei-zhen Wang , Na Li , Dong-sheng Shen
J. Microbiol. 2018;56(2):83-89.   Published online February 2, 2018
DOI: https://doi.org/10.1007/s12275-018-7286-1
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AbstractAbstract PDF
In the bacterium Pseudomonas aeruginosa, the synthesis and secretion of extracellular protease is a typical cooperative behavior regulated by quorum sensing. However, this type of cooperative behavior is easily exploited by other individuals who do not synthesize public goods, which is known as the “tragedy of the commons”. Here P. aeruginosa was inoculated into casein media with different nitrogen salts added. In casein broth, protease (a type of public good) is necessary for bacterial growth. After 30 days of sequential transfer, some groups propagated stably and avoided “tragedy of the commons”. The evolved cooperators who continued to synthesize protease were isolated from these stable groups. By comparing the characteristics of quorum sensing in these cooperators, an identical evolutionary pattern was found. A variety of cooperative behaviors regulated by quorum sensing, such as the synthesis and secretion of protease and signals, were significantly reduced during the process of evolution. Such reductions improved the efficiency of cooperation, helping to prevent cheating. In addition, the production of pyocyanin, which is regulated by the RhlIR system, increased during the process of evolution, possibly due to its role in stabilizing the cooperation. This study contributes towards our understanding of the evolution of quorum sensing of P. aeruginosa.

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  • Role of horizontal gene transfer and cooperation in rhizosphere microbiome assembly
    Simone Raposo Cotta, Armando Cavalcante Franco Dias, Rodrigo Mendes, Fernando Dini Andreote
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  • To cheat or not to cheat: cheatable and non-cheatable virulence factors in Pseudomonas aeruginosa
    Katya Dafne Guadarrama-Orozco, Caleb Perez-Gonzalez, Kokila Kota, Miguel Cocotl-Yañez, Jesús Guillermo Jiménez-Cortés, Miguel Díaz-Guerrero, Mariel Hernández-Garnica, Julia Munson, Frederic Cadet, Luis Esaú López-Jácome, Ángel Yahir Estrada-Velasco, Ana M
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    Daniel Huelgas-Méndez, Daniel Cazares, Luis David Alcaraz, Corina Diana Ceapã, Miguel Cocotl-Yañez, Toya Shotaro, Toshinari Maeda, Ana María Fernández-Presas, Oswaldo Tostado-Islas, Ana Lorena González-Vadillo, Aldo Limones-Martínez, Carlos Eduardo Hernan
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    Rhea G. Abisado, John H. Kimbrough, Brielle M. McKee, Vaughn D. Craddock, Nicole E. Smalley, Ajai A. Dandekar, Josephine R. Chandler, Rebecca E. Parales
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  • Seeding Public Goods Is Essential for Maintaining Cooperation in Pseudomonas aeruginosa
    Daniel Loarca, Dánae Díaz, Héctor Quezada, Ana Laura Guzmán-Ortiz, Abril Rebollar-Ruiz, Ana María Fernández Presas, Jimena Ramírez-Peris, Rafael Franco-Cendejas, Toshinari Maeda, Thomas K. Wood, Rodolfo García-Contreras
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Imipenem-resistant Gram-negative bacterial isolates carried by persons upon medical examination in Korea
So Yeon Kim , Sang Yop Shin , Ji-Young Rhee , Kwan Soo Ko
J. Microbiol. 2017;55(8):612-618.   Published online July 18, 2017
DOI: https://doi.org/10.1007/s12275-017-6555-8
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AbstractAbstract PDF
Carbapenem-resistant Gram-negative bacteria (CR-GNB) have emerged and disseminated worldwide, become a great concern worldwide including Korea. The prevalence of fecal carriage of imipenem-resistant Gram-negative bacteria (IRGNB) in persons in Korea was investigated. Stool samples were collected from 300 persons upon medical examination. Samples were screened for IR-GNB by using MacConkey agar with 2 μl/ml imipenem. Species were identified by 16S rRNA gene sequence analysis, and antimicrobial susceptibility was determined by the broth microdilution method. In total, 82 IR-GNB bacterial isolates were obtained from 79 (26.3%) out of 300 healthy persons. Multilocus sequence typing analysis showed very high diversity among IR P. aeruginosa, S. maltophilia, and E. cloacae isolates, and pulsedfield gel electrophoresis revealed five main pulsotypes of IR P. mirabilis. As for the presence of metallo-β-lactamases (MBLs), only one IMP-25-producing S. marcescens isolate was identified. Although only one carbapenemase-producing isolate was identified, the high colonization rates with IRGNB isolates in this study is notable because carriers may be a reservoir for the dissemination of resistant pathogens within the community as well as in health care institutions.

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  • Global mapping of antibiotic resistance rates among clinical isolates of Stenotrophomonas maltophilia: a systematic review and meta-analysis
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Antibacterial compound produced by Pseudomonas aeruginosa strain UICC B-40, an endophytic bacterium isolated from Neesia altissima
Rina Hidayati Pratiwi , Iman Hidayat , Muhammad Hanafi , Wibowo Mangunwardoyo
J. Microbiol. 2017;55(4):289-295.   Published online January 26, 2017
DOI: https://doi.org/10.1007/s12275-017-6311-0
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AbstractAbstract PDF
This study’s aim was to determine the identity of antibacte-rial compounds produced by Pseudomonas aeruginosa strain UICC B-40 and describe the antibacterial compounds’ me-chanisms of action for damaging pathogenic bacteria cells. Isolation and identification of the compounds were carried out using thin layer chromatography (TLC), nuclear mag-netic resonance (NMR) spectroscopy and liquid chromato-graphy mass spectrometry (LC-MS) analyses. Antibacterial activity was assayed via minimum inhibitory concentration (MIC) and the antibacterial compound mechanism was ob-served morphologically through scanning electron micros-copy (SEM). This study successfully identified the (2E,5E)- phenyltetradeca-2,5-dienoate antibacterial compound (mole-cular weight 300 g/mol), composed of a phenolic ester, fatty acid and long chain of aliphatic group structures. MIC values for this compound were determined at 62.5 μg/ml against Staphylococcus aureus strain ATCC 25923. The mechanism of the compound involved breaking down the bacterial cell walls through the lysis process. The (2E,5E)-phenyltetradeca- 2,5-dienoate compound exhibited inhibitory activity on the growth of Gram-positive bacteria.

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Identification of essential genes of Pseudomonas aeruginosa for its growth in airway mucus
Mohammed Abd Alrahman , Sang Sun Yoon
J. Microbiol. 2017;55(1):68-74.   Published online December 30, 2016
DOI: https://doi.org/10.1007/s12275-017-6515-3
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AbstractAbstract PDF
Pseudomonas aeruginosa has been identified as an important causative agent of airway infection, mainly in cystic fibrosis. This disease is characterized by defective mucociliary clearance induced in part by mucus hyper-production. Mucin is a major component of airway mucus and is heavily O-glycosylated, with a protein backbone. Airway infection is known to be established with bacterial adhesion to mucin. However, the genes involved in mucin degradation or utilization remain elusive. In this study, we sought to provide a genetic basis of P. aeruginosa airway growth by identifying those genes. First, using RNASeq analyses, we compared genome-wide expression profiles of PAO1, a prototype P. aeruginosa laboratory strain, grown in M9-mucin (M9M) and M9-glucose (M9G) media. Additionally, a PAO1 transposon (Tn) insertion mutants library was screened for mutants defective in growth in M9M medium. One mutant with a Tn insertion in the xcpU gene (PA3100) was determined to exhibit faulty growth in M9M medium. This gene contributes to the type II secretion system, suggesting that P. aeruginosa uses this secretion system to produce a number of proteins to break down and assimilate the mucin molecule. Furthermore, we screened the PAO1 genome for genes with protease activity. Of 13 mutants, one with mutation in PA3247 gene exhibited defective growth in M9M, suggesting that the PA3247-encoded protease plays a role in mucin utilization. Further mechanistic dissection of this particular process will reveal new drug targets, the inhibition of which could control recalcitrant P. aeruginosa infections.

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Review
MINIREVIEW] Biofilm dispersion in Pseudomonas aeruginosa
Soo-Kyoung Kim , Joon-Hee Lee
J. Microbiol. 2016;54(2):71-85.   Published online February 2, 2016
DOI: https://doi.org/10.1007/s12275-016-5528-7
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AbstractAbstract PDF
In recent decades, many researchers have written numerous articles about microbial biofilms. Biofilm is a complex community of microorganisms and an example of bacterial group behavior. Biofilm is usually considered a sessile mode of life derived from the attached growth of microbes to surfaces, and most biofilms are embedded in self-produced extracellular matrix composed of extracellular polymeric substances (EPSs), such as polysaccharides, extracellular DNAs (eDNA), and proteins. Dispersal, a mode of biofilm detachment indicates active mechanisms that cause individual cells to separate from the biofilm and return to planktonic life. Since biofilm cells are cemented and surrounded by EPSs, dispersal is not simple to do and many researchers are now paying more attention to this active detachment process. Unlike other modes of biofilm detachment such as erosion or sloughing, which are generally considered passive processes, dispersal occurs as a result of complex spatial differentiation and molecular events in biofilm cells in response to various environmental cues, and there are many biological reasons that force bacterial cells to disperse from the biofilms. In this review, we mainly focus on the spatial differentiation of biofilm that is a prerequisite for dispersal, as well as environmental cues and molecular events related to the biofilm dispersal. More specifically, we discuss the dispersal-related phenomena and mechanisms observed in Pseudomonas aeruginosa, an important opportunistic human pathogen and representative model organism for biofilm study.

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Research Support, Non-U.S. Gov'ts
Note] Inhibition of quorum sensing in Pseudomonas aeruginosa by two herbal essential oils from Apiaceae family
Ehsan Sepahi , Saeed Tarighi , Farajollah Shahriari Ahmadi , Abdolreza Bagheri
J. Microbiol. 2015;53(2):176-180.   Published online January 5, 2015
DOI: https://doi.org/10.1007/s12275-015-4203-8
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AbstractAbstract
Ferula (Ferula asafoetida L.) and Dorema (Dorema aucheri Bioss.) both from Apiaceae family were tested for their antiquorum sensing (QS) activity against Pseudomonas aeruginosa. Both essential oils exhibited anti-QS activity at 25 μg/ml of concenteration. At this concenteration Ferula fully abolished and Dorema reduced the violacein production by C. violaceum. Pyocyanin, pyoverdine, elastase and biofilm production were decreased in Ferula oil treatments. Dorema oil reduced pyoverdine and elastase production, while pyocyanin and biofilm production were not affacted. Expresion analysis of QS-dependent genes confirmed our phenotypic data. Our data introduced native Dorema and Ferula plants as novel QS and virulence inhibitors.

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J. Microbiol. 2014;52(12):1044-1049.   Published online November 29, 2014
DOI: https://doi.org/10.1007/s12275-014-4512-3
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AbstractAbstract PDF
The proinflammatory cytokine interleukin-1β plays an important role in protecting the host against airway infection; however, it can also trigger a massive influx of neutrophils into the airways, causing tissue damage. Anti-inflammatory treatments are particularly in demand for patients suffering from chronic inflammatory diseases. Sophora flavescens is a traditional herbal medicine used to reduce inflammation, but no study has examined its ability to block IL-1β production. Here, we show that S. flavescens reduced the Pseudomonas aeruginosa-induced expression of IL-1β by lung epithelial cells and macrophages. S. flavescens was also effective at reducing IL-1β production induced by either Staphylococcus aureus or phorbol 12-myristate 13-acetate, indicating that the effect is generalizable to diverse inflammatory stimuli. In addition, S. flavescens blocked the phosphorylation of IKKα/β, key upstream kinases involved in the degradation of IκBα, and the cleavage of caspase-1, a key component of the inflammasome. Thus, this study demonstrates that S. flavescens exerts its anti-inflammatory effects by blocking P. aeruginosa-mediated NF-κB/inflammasome activation and the subsequent production of IL-1β.

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AbstractAbstract PDF
4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF), a nonhalogenated furanone found in a variety of fruits, has been shown to have antimicrobial activity. However, few studies have focused on its inhibitory effect on bacterial quorum sensing (QS) at levels below the non-inhibitory concentration. In this study, 0.1 μM HDMF decreased the production of QS signal molecules and inhibited QS-controlled biofilm formation by Pseudomonas aeruginosa PAO1 without causing growth inhibition. In the presence of 0.1 and 1.0 μM HDMF, biofilm production by PAO1 was reduced by 27.8 and 42.6%, respectively, compared to that by untreated control cells. HDMF (1.0 μM) also significantly affected virulence factor expression (regulated by the las, rhl, and pqs system), resulting in a significant reduction in the production of LasA protease (53.8%), rhamnolipid (40.9%), and pyocyanin (51.4%). This HDMF-dependent inhibition of virulence factor expression was overcome by increasing the levels of two QS signal molecules of P. aeruginosa, N-(3-oxo-dodecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone, suggesting reversible competitive inhibition between HDMF and these molecules. The results of this study indicate that HDMF has great potential as an inhibitor of QS, and that it may be of value as a therapeutic agent and in biofilm control, without increasing selective pressure for resistance development.

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Superinfection Exclusion Reveals Heteroimmunity between Pseudomonas aeruginosa Temperate Phages
In-Young Chung , Hee-Won Bae , Hye-Jung Jang , Bi-o Kim , You-Hee Cho
J. Microbiol. 2014;52(6):515-520.   Published online May 29, 2014
DOI: https://doi.org/10.1007/s12275-014-4012-5
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AbstractAbstract PDF
Temperate siphophages (MP29, MP42, and MP48) were isolated from the culture supernatant of clinical Pseudomonas aeruginosa isolates. The complete nucleotide sequences and annotation of the phage genomes revealed the overall synteny to the known temperate P. aeruginosa phages such as MP22, D3112, and DMS3. Genome-level sequence analysis showed the conservation of both ends of the linear genome and the divergence at the previously identified dissimilarity regions (R1 to R9). Protein sequence alignment of the c repressor (ORF1) of each phage enabled us to divide the six phages into two groups: D3112 group (D3112, MP29, MP42, and MP48) and MP22 group (MP22 and DMS3). Superinfection exclusion was observed between the phages belonging to the same group, which was mediated by the specific interaction between the c repressor and the cognate operator. Based on these, we suggest that the temperate siphophages prevalent in the clinical strains of P. aeruginosa represent at least two distinct heteroimmunity groups.

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Reviews
REVIEW] Chronic Obstructive Pulmonary Disease (COPD): Evaluation From Clinical, Immunological and Bacterial Pathogenesis Perspectives
Daniel J. Hassett , Michael T. Borchers , Ralph J. Panos
J. Microbiol. 2014;52(3):211-226.   Published online March 1, 2014
DOI: https://doi.org/10.1007/s12275-014-4068-2
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AbstractAbstract PDF
Chronic obstructive pulmonary disease (COPD), a disease manifested by significantly impaired airflow, afflicts ~14.2 million cases in the United States alone with an estimated 63 million people world-wide. Although there are a number of causes, the predominant cause is excessive tobacco smoke. In fact, in China, there have been estimates of 315,000,000 people that smoke. Other less frequent causes are associated with indirect cigarette smoke, air pollutants, biomass fuels, and genetic mutations. COPD is often associated with heart disease, lung cancer, osteoporosis and conditions can worsen in patients with sudden falls. COPD also affects both innate and adaptive immune processes. Cigarette smoke increases the expression of matrix metalloproteases and proinflammatory chemokines and increases lung titers of natural killer cells and neutrophils. Yet, neutrophil reactive oxygen species (ROS) mediated by the phagocytic respiratory burst and phagocytosis is impaired by nicotine. In contrast to innate immunity in COPD, dendritic cells represent leukocytes recruited to the lung that link the innate immune responses to adaptive immune responses by activating naïve T cells through antigen presentation. The autoimmune process that is also a significant part of inflammation associated with COPD. Moreover, coupled with restricted FEV1 values, are the prevalence of patients with single or multiple infections by bacteria, viruses and fungi. Finally, we focus on one of the more problematic infectious agents, the Gram-negative opportunistic pathogenic bacterium, Pseudomonas aeruginosa. Specifically, we delve into the development of highly problematic biofilm infections that are highly refractory to conventional antibiotic therapies in COPD. We offer a nonconventional, biocidal treatment that may be effective for COPD airway infections as well as with combinations of current antibiotic regimens for more effective treatment outcomes and relief for patients with COPD.

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REVIEW] Perturbation of Pulmonary Immune Functions by Carbon Nanotubes and Susceptibility to Microbial Infection
Brent E. Walling , Gee W. Lau
J. Microbiol. 2014;52(3):227-234.   Published online March 1, 2014
DOI: https://doi.org/10.1007/s12275-014-3695-y
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AbstractAbstract PDF
Occupational and environmental pulmonary exposure to carbon nanotubes (CNT) is considered to be a health risk with a very low threshold of tolerance as determined by the United States Center for Disease Control. Immortalized airway epithelial cells exposed to CNTs show a diverse range of effects including reduced viability, impaired proliferation, and elevated reactive oxygen species generation. Additionally, CNTs inhibit internalization of targets in multiple macrophage cell lines. Mice and rats exposed to CNTs often develop pulmonary granulomas and fibrosis. Furthermore, CNTs have immunomodulatory properties in these animal models. CNTs themselves are proinflammatory and can exacerbate the allergic response. However, CNTs may also be immunosuppressive, both locally and systemically. Studies that examined the relationship of CNT exposure prior to pulmonary infection have reached different conclusions. In some cases, pre-exposure either had no effect or enhanced clearance of infections while other studies showed CNTs inhibited clearance. Interestingly, most studies exploring this relationship use pathogens which are not considered primary pulmonary pathogens. Moreover, harmony across studies is difficult as different types of CNTs have dissimilar biological effects. We used Pseudomonas aeruginosa as model pathogen to study how helical multi-walled carbon nanotubes (HCNTs) affected internalization and clearance of the pulmonary pathogen. The results showed that, although HCNTs can inhibit internalization through multiple processes, bacterial clearance was not altered, which was attributed to an enhanced inflammatory response caused by pre-exposure to HCNTs. We compare and contrast our findings in relation to other studies to gauge the modulation of pulmonary immune response by CNTs.

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Research Support, Non-U.S. Gov'ts
A New Quorum-Sensing Inhibitor Attenuates Virulence and Decreases Antibiotic Resistance in Pseudomonas aeruginosa
Yu-Xiang Yang , Zhen-Hua Xu , Yu-Qian Zhang , Jing Tian , Li-Xing Weng , Lian-Hui Wang
J. Microbiol. 2012;50(6):987-993.   Published online December 30, 2012
DOI: https://doi.org/10.1007/s12275-012-2149-7
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AbstractAbstract PDF
Quorum sensing (QS) has been a novel target for the treatment of infectious diseases. Here structural analogs of Pseudomonas aeruginosa autoinducer N-acyl homoserine lactone (AHL) were investigated for QS inhibitor (QSI) activity and a novel QSI was discovered, N-decanoyl-L-homoserine benzyl ester (C2). Virulence assays showed that C2 downregulated total protease and elastase activities, as well as the production of rhamnolipid, that are controlled by QS in P. aeruginosa wild-type strain PAO1 without affecting growth. C2 was also shown to inhibit swarming motility of PAO1. Using a microdilution checkerboard method, we identified synergistic interactions between C2 and several antibiotics, tobramycin, gentamycin, cefepime, and meropenem. Data from real-time RT-PCR suggested that C2 inhibited the expression of lasR (29.67%), lasI (21.57%), rhlR (28.20%), and rhlI (29.03%).

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Antibacterial Efficacy of Lytic Pseudomonas Bacteriophage in Normal and Neutropenic Mice Models
Birendra R. Tiwari , Shukho Kim , Marzia Rahman , Jungmin Kim
J. Microbiol. 2011;49(6):994-999.   Published online December 28, 2011
DOI: https://doi.org/10.1007/s12275-011-1512-4
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AbstractAbstract PDF
Recently, lytic bacteriophages (phages) have been focused on treating bacterial infectious diseases. We investigated the protective efficacy of a novel Pseudomonas aeruginosa phage, PA1Ø, in normal and neutropenic mice. A lethal dose of P. aeruginosa PAO1 was administered via the intraperitoneal route and a single dose of PA1Ø with different multiplicities of infection (MOI) was treated into infected mice. Immunocompetent mice infected with P. aeruginosa PAO1 were successfully protected by PA1Ø of 1 MOI, 10 MOI or 100 MOI with 80% to 100% survival rate. No viable bacteria were found in organ samples after 48 h of the phage treatment. Phage clearing patterns were different in the presence or absence of host bacteria but PA1Ø disappeared from all organs after 72 h except spleen in the presence of host bacteria. On the contrary, PA1Ø treatment could not protect neutropenic mice infected with P. aeruginosa PAO1 even though could extend their lives for a short time. In in vitro phage-neutrophil bactericidal test, a stronger bactericidal effect was observed in phage-neutrophil co-treatment than in phage single treatment without neutrophils, suggesting phage-neutrophil co-work is essential for the efficient killing of bacteria in the mouse model. In conclusion, PA1Ø can be possibly utilized in future phage therapy endeavors since it exhibited strong protective effects against virulent P. aeruginosa infection.

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Detection of Pseudomonas aeruginosa Carried a New Array of Gene Cassettes within Class 1 Integron Isolated from a Teaching Hospital in Nanjing, China
Yuan Wu† , Hui Li† , Jun Li , Zu Hu Huang
J. Microbiol. 2008;46(6):687-691.   Published online December 24, 2008
DOI: https://doi.org/10.1007/s12275-008-0021-6
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AbstractAbstract PDF
We report here novel array of gene cassettes found in single variable region of class 1 integron disseminated in Pseudomonas aeruginosa isolated from a teaching hospital in Nanjing, Jiangsu Province, China. 29 of 47 (61%) P. aeruginosa strains were confirmed haboured class 1 integron, and all the positive strains have the same variable region confirmed by PCR and RFLP methods. The variable region contained an unreported order of four gene cassettes aac(6’)-II-aadA13-cmlA8-oxa 10. Of those, cmlA8 gene was a variant of cmlA5 encoding non-enzymatic protein which putatively confer resistance to chloramphenicol. Susceptibility testing revealed multidrug-resistant mechanisms were involved in the class 1 integron positive clinical isolates. And the class 1 integron located on an about 15 kb transferable plasmid was certified by conjugation experiment and plasmid DNA analysis. The macro restriction profile indicated those clinical strains were clonally related.

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  • Distribution and Molecular Characterization of Resistance Gene Cassettes Containing Class 1 Integrons in Multi-Drug Resistant (MDR) Clinical Isolates of Pseudomonas aeruginosa


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Modulation of Secreted Virulence Factor Genes by Subinhibitory Concentrations of Antibiotics in Pseudomonas aeruginosa
Lixin Shen , Ying Shi , Dan Zhang , Jinhua Wei , Michael G. Surette , Kangmin Duan
J. Microbiol. 2008;46(4):441-447.   Published online August 31, 2008
DOI: https://doi.org/10.1007/s12275-008-0054-x
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AbstractAbstract PDF
Recent studies have shown that subinhibitory antibiotics play important roles in regulating bacterial genes including virulence factor genes. In this study, the expression of 13 secreted virulence related gene clusters of Pseudomonas aeruginosa, an important opportunistic pathogen, was examined in the presence of subinhibitory concentrations of 4 antibiotics: vancomycin, tetracycline, ampicilin and azithromycin. Activation of gene expression was observed with phzA1, rhlAB, phzA2, lasB, exoY, and exoS. Subinhibitory concentrations of vancomycin resulted in more than 10-fold increase of rhlAB and phzA2 transcription. Both rhamnolipid production and pyocyanin production were significantly elevated, correlating phenotypes with the increased transcription. P. aeruginosa swarming and swimming motility also increased. Similar results were observed with subinhibitory tetracycline, azithromycin and ampicillin. These results indicate that the antibiotics at low concentrations can up-regulate virulence factors and therefore influence bacterial pathogenesis.

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    D. G. Deryabin, K. S. Inchagova
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    Laura Selan, Gianluca Vrenna, Evaristo Ettorre, Rosanna Papa, Marco Artini
    Journal of Chemotherapy.2018; 30(6-8): 384.     CrossRef
  • Alterations of growth rate and gene expression levels of UPEC by antibiotics at sub-MIC
    Defne Gümüş, Fatma Kalaycı-Yüksek, Emre Yörük, Gülşen Uz, Eşref Çelik, Cansu Arslan, Elif Merve Aydın, Cem Canlı, Mine Anğ-Küçüker
    Folia Microbiologica.2018; 63(4): 451.     CrossRef
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    D. G. Deryabin, K. S. Inchagova
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    Applied and Environmental Microbiology.2017;[Epub]     CrossRef
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    Shekoufeh Roudashti, Habib Zeighami, Hesam Mirshahabi, Shahin Bahari, Ali Soltani, Fakhri Haghi
    World Journal of Microbiology and Biotechnology.2017;[Epub]     CrossRef
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    Christina N. Krute, Kelsey L. Krausz, Mary A. Markiewicz, Jason A. Joyner, Srijana Pokhrel, Pamela R. Hall, Jeffrey L. Bose, C. Vieille
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    Vimla Chaudhari, Haren Gosai, Shreya Raval, Vijay Kothari
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Effect of Titanium Ion and Resistance Encoding Plasmid of Pseudomonas aeruginosa ATCC 10145
Sung Min Park , Hyun Soo Kim , Tae Shick Yu
J. Microbiol. 2006;44(3):255-262.
DOI: https://doi.org/2388 [pii]
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Titanium and its alloys are technically superior and cost-effective materials, with a wide variety of aerospace, industrial, marine, and commercial applications. In this study, the effects of titanium ions on bacterial growth were evaluated. Six strains of bacteria known to be resistant to both metal ions and antibiotics were used in this study. Two strains, Escherichia coli ATCC 15489, and Pseudomonas aeruginosa ATCC 10145, proved to be resistant to titanium ions. Plasmid-cured P. aeruginosa resulted in the loss of one or more resistance markers, indicating plasmid-encoded resistance. The plasmid profile of P. aeruginosa revealed the presence of a 23-kb plasmid. The plasmid was isolated and transformed into DH5α. Interestingly, the untransformed DH5α did not grow in 300 mg/l titanium ions, but the transformed DH5α grew quite well under such conditions. The survival rate of the transformed DH5α also increased more than 3-fold compared to that of untransformed DH5α.
Microarray-Mediated Transcriptome Analysis of the Tributyltin (TBT)-Resistant Bacterium Pseudomonas aeruginosa 25W in the Presence of TBT
Santosh K. Dubey , Tsutomu Tokashiki , Satoru Suzuki
J. Microbiol. 2006;44(2):200-205.
DOI: https://doi.org/2364 [pii]
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AbstractAbstract PDF
The tributyltin (TBT)-resistant bacterium, Pseudomonas aeruginosa 25W, which was isolated in seawater from the Arabian Sea, was subjected to transcriptome analysis in the presence of high concentrations of TBT. Only slight effects were observed at TBT concentration of 50 μM, but exposure to 500 μM resulted in the upregulation of 6 genes and the downregulation of 75. Among the 75 downregulated genes, 53% (40 out of 75) were of hypothetical function, followed by 14 transcriptional regulation- and translationassociated genes. The results of this study indicated that although the 25W strain was highly resistant to TBT, high concentrations of TBT result in toxic effect on the transcriptional and translational levels. The target genes likely belong to a specific category of transcription- and translation-associated genes rather than to other gene categories.
Conserved Virulence Factors of Pseudomonas aeruginosa are Required for Killing Bacillus subtilis
Shin-Young Park , Yun-Jeong Heo , Young-Seok Choi , Eric Deziel , You-Hee Cho
J. Microbiol. 2005;43(5):443-450.
DOI: https://doi.org/2277 [pii]
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AbstractAbstract PDF
The multi-host pathogen, Pseudomonas aeruginosa, possesses an extraordinary versatility which makes it capable of surviving the adverse conditions provided by environmental, host, and, presumably, competing microbial factors in its natural habitats. Here, we investigated the P. aeruginosa-Bacillus subtilis interaction in laboratory conditions and found that some P. aeruginosa strains can outcompete B. subtilis in mixed planktonic cultures. This is accompanied by the loss of B. subtilis viability. The bactericidal activity of P. aeruginosa is measured on B. subtilis plate cultures. The bactericidal activity is attenuated in pqsA, mvfR, lasR, pilB, gacA, dsbA, rpoS, and phnAB mutants. These results suggest that P. aeruginosa utilizes a subset of conserved virulence pathways in order to survive the conditions provided by its bacterial neighbors.
Fungal-sporulation suppressing substances produced by pseudomonas aeruginosa KMCS-1
Min, Bu Yong , Shim, Jae Young , Kim, Kun Woo , Lee, Jong Kyu , Yoon, Kwon Sang
J. Microbiol. 1996;34(3):284-288.
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Among the bacteria isolated form compost piles of cattle excretion in a pasture located at the suburbs of Chunchon city, Pseudomonas aeruginosa KMCS-1 was selected for the test of antifungal substances produced. Six fractions were separated by silica gel column chromatography, and then the antifungal activity of each fraction was assayed against Escherichia coli, Bacillus subtilis, Candida albicans, Rhizopus sp., Aspergillus nidulans, Coprinus cinereus, and Pyricularia oryzae by paper disc method. Two fractions showed significant suppressive activities against A. nidulans, C. cinereus, and P. oryzae; however, their mycelial growth was not affected by neither of these fractions. Inhibitory activities of these fractions to sporulation was assayed at the concentration of 50. 25, 12. 5, and 6.25 ㎍/ml and the average inhibition rates against sporulation of A. nidulans, C. cinereus, and P. oryzae were 94.0, 98.3, and 77.9%, respectively. Further purification and analysis of active substances are now being conducted.
Microscopic Examination of the Suppressive Action of Antifungal Substances from Pseudomonas aeruginosa on Asexual Sporulation of Fungi
Yoon, Kwon S. , Min, Bu Y. , Choi, Hyoung T. , Lee, Jong K. , Kim, Kun W.
J. Microbiol. 1999;37(1):27-34.
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AbstractAbstract PDF
Two fractions with unusual antifungal activity that suppress asexual sporulation of several fungi were obtained from culture filtrate of Pseudomonas aeruginosa and were partially purified through the repeated silicagel flash column chromatographies. The sporulation-suppressive actions of these fractions in Aspergillus nidulans, Rhizopus stolonifer, and Coprinus cinereus, were analyzed by light and electron microscopes. The germination ability of the spores produced in the presence of these fractions were also checked to determine the persistent effects of these antifungal substances on the next generation. Light microscopic observation of developing sporangia of R. stolonifer grown in the presence of both fractions revealed that the significant number of sporangia failed to reach maturity, and frequently, uncontrolled growths of hyphae and rhizoids from the sporangiophores were found. In A. nidulans addition of these fractions appeared to cause different classes of morphological abnormality in conidia development, which included aborted formation of conidiogenous cells from the apex of conidiophores and enhanced hyphal growths either at the tip or middle of the conidiophores. Germination abilities of spores obtained from the cultures grown in the presence of antifungal fractions were 40∼60% in Aspergillus, 50∼80% in Coprinus (thallic spores), and 30∼40% in Rhizopus compared to those of normal spores.

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