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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Main Authors: 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
Format: Article
Language:English
Published: AIMS Press 2018-03-01
Series:AIMS Microbiology
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Online Access:http://www.aimspress.com/microbiology/article/1860/fulltext.html
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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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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 &amp; Immunology, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, Department of Microbiology &amp; Immunology, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, Department of Microbiology &amp; 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 &amp; Immunology, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, Department of Microbiology &amp; Immunology, University of British Columbia, Vancouver, BC, CanadaCentre for Microbial Diseases and Immunity Research, Department of Microbiology &amp; 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 &amp; 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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