Mutation of retS, encoding a putative hybrid two-component regulatory protein in Pseudomonas aeruginosa, attenuates multiple virulence mechanisms

Zolfaghar, Irandokht; Angus, Annette A.; Kang, Pil Jung; To, A Thesis Submitted; Evans, David J.; Fleiszig, Suzanne M. J.

doi:10.1016/j.micinf.2005.04.017

Cited by 59 publications

(55 citation statements)

References 65 publications

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“…This process represents the positive activation loop of the T3SS that is triggered by cell contact in vivo and can be mimicked by calcium depletion in vitro. Besides this major regulatory operon, other factors regulate T3SS expression, including cyclic AMP with Vfr, the Pseudomonas catabolite repression homologue (Wolfgang et al, 2003), PtrA (Ha et al, 2004) and the RetS/LadS/GacAS two-component regulatory systems (Goodman et al, 2004;Laskowski et al, 2004;Ventre et al, 2006;Zolfaghar et al, 2005). Taken together, these published data indicate that P. aeruginosa uses a complex set of signalling pathways both to activate and to repress T3SS expression in response to extracellular and intracellular triggers (Yahr & Wolfgang, 2006).…”

Section: Introductionmentioning

confidence: 98%

High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system: implications for tryptophan catabolites

et al. 2008

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Section: Introductionmentioning

confidence: 98%

High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system: implications for tryptophan catabolites

et al. 2008

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“…The unusual hybrid sensor kinase RetS (Fig. 1A) is required for TTSS activation, concomitant repression of biofilm formation, and colonization/dissemination in murine acute infection models (Goodman et al 2004;Laskowski et al 2004;Zolfaghar et al 2005). Genes under RetS control are inversely regulated by two other sensor kinases: GacS and LadS.…”

mentioning

confidence: 99%

Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen

Goodman¹,

Merighi²,

Hyodo³

et al. 2009

Genes Dev.

273

297

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The genome of the opportunistic pathogen Pseudomonas aeruginosa encodes over 60 two-component sensor kinases and uses several (including RetS and GacS) to reciprocally regulate the production of virulence factors involved in the development of acute or chronic infections. We demonstrate that RetS modulates the phosphorylation state of GacS by a direct and specific interaction between these two membrane-bound sensors. The RetS-GacS interaction can be observed in vitro, in heterologous systems in vivo, and in P. aeruginosa. This function does not require the predicted RetS phosphorelay residues and provides a mechanism for integrating multiple signals without cross-phosphorylation from sensors to noncognate response regulators. These results suggest that multiple two-component systems found in a single bacterium can form multisensor signaling networks while maintaining specific phosphorelay pathways that remain insulated from detrimental cross-talk. Two-component system (TCS) signaling pathways are a major signaling mechanism in bacteria and archaea, and are also found in simple eukaryota and higher plants (Wolanin et al. 2002). These diverse organisms capitalize on TCS pathways to monitor critical external and internal stimuli (including levels of nutrients, concentration of ions and gases, temperature, redox states, and cell density) and translate these signals into adaptive responses. Classical TCS pathways share a conserved core architecture: a homodimerizing histidine kinase protein domain (the ''sensor'') and a cognate receiver domain (the ''response regulator''), coupled mechanistically through a histidine-aspartic acid phosphorelay (Stock et al. 2000). Most cognate sensor response regulator pairs are also linked genetically, encoded by adjacent loci in the chromosome (Alm et al. 2006). Although a single bacterial species can encode up to hundreds of genes specifying TCS pathways, it appears that these systems are insulated against detrimental cross-phosphorylation between sensors and noncognate response regulators (Bijlsma and Groisman 2003;Baker and Stock 2007;Laub and Goulian 2007). The identification of multistep phosphorelays (with intermediary proteins between sensor and regulator) and branched pathways (phosphotransfer between one sensor and multiple response regulators and vice versa) (Laub and Goulian 2007) suggests that TCS pathways have the capacity to form sensitive and complex signaling networks.In contrast to microorganisms with restricted habitats, the genomes of bacteria capable of occupying a number of diverse environments typically contain a disproportionately large number of genes encoding signal transduction and regulatory systems, including TCSs that allow them to sense and respond to a wide range of environmental signals. For opportunistic bacterial pathogens, a number of these systems regulate the expression of genes necessary for transitioning from the environmental reservoir to the host, overcoming innate defense mechanisms and initiating the disease process. The bacterial pathogen ...

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“…Two hybrid sensors lacking cognate sensor kinases, RetS and LadS, have antagonistic roles relative to one another, and exert negative and positive effects respectively on rsmZ expression Laskowski, 2006;Ventre, 2006). retS (regulator of exopolysaccharides and T3S) and rsmA mutants have similar phenotypes including hyperbiofilm formation, reduced T3S expression and cytotoxicity, and diminished twitching motility (decreased Tfp expression) (Pessi, 2001;Zolfaghar, 2005;Goodman, 2009). LadS (lost adherence sensor) was identified in a transposon library screen for mutants reduced in the ability to form biofilms (Vallet, 2001).…”

Section: Additional Regulators Of the Gacs/a Systemmentioning

confidence: 99%

Global Regulatory Pathways and Cross-talk ControlPseudomonas aeruginosaEnvironmental Lifestyle and Virulence Phenotype

Coggan

Wolfgang

2012

Current Issues in Molecular Biology

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Pseudomonas aeruginosa is a metabolically versatile environmental bacterium and an opportunistic human pathogen that relies on numerous signaling pathways to sense, respond, and adapt to fluctuating environmental cues. Although the environmental signals sensed by these pathways are poorly understood, they are largely responsible for determining whether P. aeruginosa adopts a planktonic or sessile lifestyle. These environmental lifestyle extremes parallel the acute and chronic infection phenotypes observed in human disease. In this review, we focus on four major pathways (cAMP/Vfr and c-di-GMP signaling, quorum sensing, and the Gac/Rsm pathway) responsible for sensing and integrating external stimuli into coherent regulatory control at the transcriptional, translational, and post-translational level. A common theme among these pathways is the inverse control of factors involved in promoting motility and acute infection and those associated with biofilm formation and chronic infection. In many instances these regulatory pathways influence one another, forming a complex network allowing P. aeruginosa to assimilate numerous external signals into an integrated regulatory circuit that controls a lifestyle continuum.

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Mutation of retS, encoding a putative hybrid two-component regulatory protein in Pseudomonas aeruginosa, attenuates multiple virulence mechanisms

Cited by 59 publications

References 65 publications

High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system: implications for tryptophan catabolites

High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system: implications for tryptophan catabolites

Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen

Global Regulatory Pathways and Cross-talk ControlPseudomonas aeruginosaEnvironmental Lifestyle and Virulence Phenotype

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