Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in <em>Pseudomonas aeruginosa</em>

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; 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

doi:10.3934/microbiol.2018.1.173

AIMS Microbiology

2018, Volume 4, Issue 1: 173-191. doi: 10.3934/microbiol.2018.1.173

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Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in Pseudomonas aeruginosa

1.
Centre for Microbial Diseases and Immunity Research, Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, Canada
2.
Microbiology of Natural and Technical Interfaces Department, Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany

Received: 14 December 2017 Accepted: 26 February 2018 Published: 08 March 2018

The rapid adaptation of the opportunistic bacterial pathogen Pseudomonas aeruginosa 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.
- Pseudomonas aeruginosa,
- two-component regulatory systems,
- cytotoxicity,
- motility,
- adherence,
- biofilm,
- FleSR,
- PilSR,
- WspR
Citation: 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 Pseudomonas aeruginosa[J]. AIMS Microbiology, 2018, 4(1): 173-191. doi: 10.3934/microbiol.2018.1.173

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Abstract

The rapid adaptation of the opportunistic bacterial pathogen Pseudomonas aeruginosa 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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