<i>Pseudomonas aeruginosa fimL</i> regulates multiple virulence functions by intersecting with Vfr‐modulated pathways

Whitchurch, Cynthia B.; Beatson, Scott A.; Comolli, James C.; Jakobsen, Thania; Sargent, Jennifer L.; Bertrand, Jacob J.; West, Joyce T.; Klausen, Mikkel; Waite, Leslie L.; Kang, Pil Jung; Tolker‐Nielsen, Tim; Mattick, John S.; Engel, Joanne N.

doi:10.1111/j.1365-2958.2005.04479.x

Cited by 92 publications

(110 citation statements)

References 83 publications

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“…As our knowledge of bacterial gene regulation advances, the coordinate regulation of virulence factors is elucidated (7,24,43,44). An understanding of how this regulation occurs is central to determining how to counter these traits.…”

Section: Discussionmentioning

confidence: 99%

The Pseudomonas aeruginosa Ribbon-Helix-Helix DNA-Binding Protein AlgZ (AmrZ) Controls Twitching Motility and Biogenesis of Type IV Pili

et al. 2006

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Pseudomonas aeruginosa is an opportunistic pathogen that is commonly found in water and soil. In order to colonize surfaces with low water content, P. aeruginosa utilizes a flagellum-independent form of locomotion called twitching motility, which is dependent upon the extension and retraction of type IV pili. This study demonstrates that AlgZ, previously identified as a DNA-binding protein absolutely required for transcription of the alginate biosynthetic operon, is required for twitching motility. AlgZ may be required for the biogenesis or function of type IV pili in twitching motility. Transmission electron microscopy analysis of an algZ deletion in nonmucoid PAO1 failed to detect surface pili. To examine expression and localization of PilA (the major pilin subunit), whole-cell extracts and cell surface pilin preparations were analyzed by Western blotting. While the PilA levels present in whole-cell extracts were similar for wild-type P. aeruginosa and P. aeruginosa with the algZ deletion, the amount of PilA on the surface of the cells was drastically reduced in the algZ mutant. Analysis of algZ and algD mutants indicates that the DNA-binding activity of AlgZ is essential for the regulation of twitching motility and that this is independent of the role of AlgZ in alginate expression. These data show that AlgZ DNA-binding activity is required for twitching motility independently of its role in alginate production and that this involves the surface localization of type IV pili. Given this new role in twitching motility, we propose that algZ (PA3385) be designated amrZ (alginate and motility regulator Z).

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Section: Discussionmentioning

confidence: 99%

The Pseudomonas aeruginosa Ribbon-Helix-Helix DNA-Binding Protein AlgZ (AmrZ) Controls Twitching Motility and Biogenesis of Type IV Pili

et al. 2006

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“…The decrease in expression of TFP and TTSS genes in strains lacking a functional FimL is likely indirect and due to the decreased expression of vfr in a fimL mutant (62). FimL has sequence similarity to ChpA, a protein in P. aeruginosa identified as important for twitching motility (63).…”

Section: What Molecular Mechanisms Integrate Expression Of Genes Requmentioning

confidence: 99%

“…Recently, Whitchurch and colleagues (62) reported the identification of FimL (PA1822), a protein required for TFP production and TTSS gene expression. The decrease in expression of TFP and TTSS genes in strains lacking a functional FimL is likely indirect and due to the decreased expression of vfr in a fimL mutant (62).…”

Section: What Molecular Mechanisms Integrate Expression Of Genes Requmentioning

confidence: 99%

Keeping Their Options Open: Acute versus Persistent Infections

2006

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“…The Chp system, a complex two-component signal transduction system that resembles the flagellar chemotaxis system, has previously been implicated as a regulator of TFP; in the absence of Chp proteins, P. aeruginosa exhibits defective TFP assembly and twitching motility, although pilin subunits are still produced (8). In addition, the Chp system has been shown to regulate the level of the signaling molecule cAMP (9, 10), which in turn binds to the transcription factor Vfr (virulence factor regulator) to activate the transcription of more than 100 genes (11).…”

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confidence: 99%

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

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Engel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Bacteria have evolved a wide range of sensing systems to appropriately respond to environmental signals. Here we demonstrate that the opportunistic pathogen Pseudomonas aeruginosa detects contact with surfaces on short timescales using the mechanical activity of its type IV pili, a major surface adhesin. This signal transduction mechanism requires attachment of type IV pili to a solid surface, followed by pilus retraction and signal transduction through the Chp chemosensory system, a chemotaxis-like sensory system that regulates cAMP production and transcription of hundreds of genes, including key virulence factors. Like other chemotaxis pathways, pili-mediated surface sensing results in a transient response amplified by a positive feedback that increases type IV pili activity, thereby promoting long-term surface attachment that can stimulate additional virulence and biofilm-inducing pathways. The methyl-accepting chemotaxis protein-like chemosensor PilJ directly interacts with the major pilin subunit PilA. Our results thus support a mechanochemical model where a chemosensory system measures the mechanically induced conformational changes in stretched type IV pili. These findings demonstrate that P. aeruginosa not only uses type IV pili for surface-specific twitching motility, but also as a sensor regulating surface-induced gene expression and pathogenicity.surface sensing | mechanotransduction | type IV pili | virulence N umerous bacterial species exhibit a range of behaviors that are specific to life on surfaces. For many pathogens, surfacespecific phenotypes are often associated with virulent activity, because many infection strategies require contact with a host (1). For example, in Pseudomonas aeruginosa, the type III secretion system, which infects by injecting toxins, requires attachment of individual cells to host-cell membranes (2). The genetic pathways that regulate P. aeruginosa secretion systems have been well characterized (3), but the environmental signals that activate these pathways remain poorly defined (4). Given the requirement for host-cell contact for efficient infection, P. aeruginosa could leverage surface contact as a signal to properly activate and coordinate pathogenicity. Indeed, our laboratory recently demonstrated that prolonged association with a solid surface contributes to P. aeruginosa pathogenicity when bacteria and host cells are forced together (5). Here we address the fundamental question of how bacteria rapidly sense surface contact and transduce this input into a cellular response over short timescales.Surface-specific behaviors require intimate contact between cells and substrate. In P. aeruginosa, contact is mediated by several adhesins, particularly type IV pili (TFP). TFP are long, motorized fimbriae that also provide cells with surface-specific twitching motility and are essential to virulence and biofilm formation (6, 7). Successive TFP extension, attachment, and retraction promote intimate association with surfaces and motility along them. Because TFP dynamically int...

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Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr‐modulated pathways

Cited by 92 publications

References 83 publications

The Pseudomonas aeruginosa Ribbon-Helix-Helix DNA-Binding Protein AlgZ (AmrZ) Controls Twitching Motility and Biogenesis of Type IV Pili

The Pseudomonas aeruginosa Ribbon-Helix-Helix DNA-Binding Protein AlgZ (AmrZ) Controls Twitching Motility and Biogenesis of Type IV Pili

Keeping Their Options Open: Acute versus Persistent Infections

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

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