Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em>
The rapid adaptation of the opportunistic bacterial pathogen <em>Pseudomonas aeruginosa</em> to various growth modes and environmental conditions is controlled in part through diverse two-component regulatory systems. Some of these systems are well studied, but the majority are poorly ch...
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AIMS Press
2018-03-01
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author | Shaan L. Gellatly Manjeet Bains Elena B.M. Breidenstein Janine Strehmel Fany Reffuveille Patrick K. Taylor Amy T.Y. Yeung Joerg Overhage Robert E.W. Hancock |
author_facet | Shaan L. Gellatly Manjeet Bains Elena B.M. Breidenstein Janine Strehmel Fany Reffuveille Patrick K. Taylor Amy T.Y. Yeung Joerg Overhage Robert E.W. Hancock |
author_sort | Shaan L. Gellatly |
collection | DOAJ |
description | The rapid adaptation of the opportunistic bacterial pathogen <em>Pseudomonas aeruginosa</em> to various growth modes and environmental conditions is controlled in part through diverse two-component regulatory systems. Some of these systems are well studied, but the majority are poorly characterized, even though it is likely that several of these systems contribute to virulence. Here, we screened all available strain PA14 mutants in 50 sensor kinases, 50 response regulators and 5 hybrid sensor/regulators, for contributions to cytotoxicity against cultured human bronchial epithelial cells, as assessed by the release of cytosolic lactate dehydrogenase. This enabled the identification of 8 response regulators and 3 sensor kinases that caused substantial decreases in cytotoxicity, and 5 response regulators and 8 sensor kinases that significantly increased cytotoxicity by 15–58% or more. These regulators were additionally involved in motility, adherence, type 3 secretion, production of cytotoxins, and the development of biofilms. Here we investigated in more detail the roles of FleSR, PilSR and WspR. Not all cognate pairs contributed to cytotoxicity (e.g. PhoPQ, PilSR) in the same way and some differences could be detected between the same mutants in PAO1 and PA14 strain backgrounds (e.g. FleSR, PhoPQ). This study highlights the potential importance of these regulators and their downstream targets on pathogenesis and demonstrates that cytotoxicity can be regulated by several systems and that their contributions are partly dependent on strain background. |
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last_indexed | 2024-12-19T10:29:14Z |
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spelling | doaj.art-74975aa3162845e4be7600c2879b8ece2022-12-21T20:25:48ZengAIMS PressAIMS Microbiology2471-18882018-03-014117319110.3934/microbiol.2018.1.173microbiol-04-01-173Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em>Shaan L. Gellatly0Manjeet Bains1Elena B.M. Breidenstein2Janine Strehmel3Fany Reffuveille4Patrick K. Taylor5Amy T.Y. Yeung6Joerg Overhage7Robert E.W. Hancock8Centre for Microbial Diseases and Immunity Research, Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, CanadaMicrobiology of Natural and Technical Interfaces Department, Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Karlsruhe, GermanyCentre for Microbial Diseases and Immunity Research, Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, CanadaMicrobiology of Natural and Technical Interfaces Department, Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Karlsruhe, GermanyCentre for Microbial Diseases and Immunity Research, Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, CanadaThe rapid adaptation of the opportunistic bacterial pathogen <em>Pseudomonas aeruginosa</em> to various growth modes and environmental conditions is controlled in part through diverse two-component regulatory systems. Some of these systems are well studied, but the majority are poorly characterized, even though it is likely that several of these systems contribute to virulence. Here, we screened all available strain PA14 mutants in 50 sensor kinases, 50 response regulators and 5 hybrid sensor/regulators, for contributions to cytotoxicity against cultured human bronchial epithelial cells, as assessed by the release of cytosolic lactate dehydrogenase. This enabled the identification of 8 response regulators and 3 sensor kinases that caused substantial decreases in cytotoxicity, and 5 response regulators and 8 sensor kinases that significantly increased cytotoxicity by 15–58% or more. These regulators were additionally involved in motility, adherence, type 3 secretion, production of cytotoxins, and the development of biofilms. Here we investigated in more detail the roles of FleSR, PilSR and WspR. Not all cognate pairs contributed to cytotoxicity (e.g. PhoPQ, PilSR) in the same way and some differences could be detected between the same mutants in PAO1 and PA14 strain backgrounds (e.g. FleSR, PhoPQ). This study highlights the potential importance of these regulators and their downstream targets on pathogenesis and demonstrates that cytotoxicity can be regulated by several systems and that their contributions are partly dependent on strain background.http://www.aimspress.com/microbiology/article/1860/fulltext.html<em>Pseudomonas aeruginosa</em>two-component regulatory systemscytotoxicitymotilityadherencebiofilmFleSRPilSRWspR |
spellingShingle | Shaan L. Gellatly Manjeet Bains Elena B.M. Breidenstein Janine Strehmel Fany Reffuveille Patrick K. Taylor Amy T.Y. Yeung Joerg Overhage Robert E.W. Hancock Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em> AIMS Microbiology <em>Pseudomonas aeruginosa</em> two-component regulatory systems cytotoxicity motility adherence biofilm FleSR PilSR WspR |
title | Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em> |
title_full | Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em> |
title_fullStr | Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em> |
title_full_unstemmed | Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em> |
title_short | Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em> |
title_sort | novel roles for two component regulatory systems in cytotoxicity and virulence related properties in em pseudomonas aeruginosa em |
topic | <em>Pseudomonas aeruginosa</em> two-component regulatory systems cytotoxicity motility adherence biofilm FleSR PilSR WspR |
url | http://www.aimspress.com/microbiology/article/1860/fulltext.html |
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