Infection of human mucosal tissue by Pseudomonas aeruginosa requires sequential and mutually dependent virulence factors and a novel pilus-associated adhesin

Heiniger, Ryan W.; Winther‐Larsen, Hanne C.; Pickles, Raymond J.; Koomey, Michael; Wolfgang, Matthew C.

doi:10.1111/j.1462-5822.2010.01461.x

Cited by 105 publications

(145 citation statements)

References 67 publications

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“…Therefore, PilY1 affects short timescale mechanosensation but is not absolutely required. This effect could be explained by the fact that pilY1 mutants are partially defective in TFP assembly and retraction (20).…”

Section: Resultsmentioning

confidence: 99%

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

Persat

Inclán

Engel

et al. 2015

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

364

398

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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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Section: Resultsmentioning

confidence: 99%

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

Persat

Inclán

Engel

et al. 2015

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

364

398

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“…Those data led to a focus on development of anti-P. aeruginosa vaccines containing peptides corresponding to the D region (71,72,75,162,216). Newer information showing that the minor pilins are present in sheared pilus fractions (154,416) and that the orthologous PilC1 or PilC2 (Neisseria and Kingella) and PilY1 (Pseudomonas) proteins are potentially pilus associated and required for adherence to-and manipulation of-the host (174,204,217,288,289,384) suggests that additional studies are needed to unequivocally identify all T4aP adhesins. Given the wide range of surfaces to which T4P bind, there may be multiple players that contribute to adherence under specific circumstances.…”

Section: Figmentioning

confidence: 99%

“…N. meningitidis isolates use PilC1 and PilC2 to adhere to the uropods of neutrophils in order to escape phagocytosis (362). P. aeruginosa expresses an integrinbinding PilC homolog, called PilY1, that requires the T4P system for surface localization, although its direct association with pili has not yet been demonstrated convincingly (13,53,174,204). Mutation of PilY1 homologs in plant pathogens has also been associated with defects in motility and biofilm formation (252,310).…”

Section: Adherence and Aggregationmentioning

confidence: 99%

Type IV Pilin Proteins: Versatile Molecular Modules

Giltner

Nguyen

Burrows

2012

Microbiol Mol Biol Rev

412

519

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SUMMARYType IV pili (T4P) are multifunctional protein fibers produced on the surfaces of a wide variety of bacteria and archaea. The major subunit of T4P is the type IV pilin, and structurally related proteins are found as components of the type II secretion (T2S) system, where they are called pseudopilins; of DNA uptake/competence systems in both Gram-negative and Gram-positive species; and of flagella, pili, and sugar-binding systems in the archaea. This broad distribution of a single protein family implies both a common evolutionary origin and a highly adaptable functional plan. The type IV pilin is a remarkably versatile architectural module that has been adopted widely for a variety of functions, including motility, attachment to chemically diverse surfaces, electrical conductance, acquisition of DNA, and secretion of a broad range of structurally distinct protein substrates. In this review, we consider recent advances in this research area, from structural revelations to insights into diversity, posttranslational modifications, regulation, and function.

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“…To confirm that the loss of type IV pili or the loss of the replicative form of bacteriophage Pf4 results in cells that can tolerate the loss of both MvaT and MvaU, we tested the effect of deleting the pilY1 and PA0728 genes, as pilY1 is known to be required for the production of type IV pili and PA0728 is predicted to be important for the production of Pf4; pilY1 encodes a protein that is typically required for type IV pilus biogenesis (23,41) and was hit in our transposon mutant screen (Table 1), whereas PA0728 is a gene whose ortholog in P. aeruginosa strain PA14 has been shown to be required for production of the replicative form of phage Pf5, a phage that is highly related to Pf4 (36). We therefore deleted the pilY1 and PA0728 genes in our PAO1 ⌬sspB ⌬mvaU MvaT-VDAS4 depletion strain, creating strains PAO1 ⌬sspB ⌬mvaU ⌬pilY1 MvaT-VDAS4 and PAO1 ⌬sspB ⌬mvaU ⌬PA0728 MvaT-VDAS4, respectively.…”

Section: Identification Of Transposon Insertion Mutants That Toleratementioning

confidence: 99%

Basis for the Essentiality of H-NS Family Members in Pseudomonas aeruginosa

Castang

Dove

2012

J. Bacteriol.

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ABSTRACTMembers of the histone-like nucleoid-structuring (H-NS) family of proteins have been shown to play important roles in silencing gene expression and in nucleoid compaction. InPseudomonas aeruginosa, the two H-NS family members MvaT and MvaU are thought to bind the same AT-rich regions of the chromosome and function coordinately to control a common set of genes. Here we present evidence that the loss of both MvaT and MvaU cannot be tolerated because it results in the production of Pf4 phage that superinfect and kill cells or inhibit their growth. Using a ClpXP-based protein depletion system in combination with transposon mutagenesis, we identify mutants ofP. aeruginosathat can tolerate the depletion of MvaT in an ΔmvaUmutant background. Many of these mutants contain insertions in genes encoding components, assembly factors, or regulators of type IV pili or contain insertions in genes of the prophage Pf4. We demonstrate that cells that no longer produce type IV pili or that no longer produce the replicative form of the Pf4 genome can tolerate the loss of both MvaT and MvaU. Furthermore, we show that the loss of both MvaT and MvaU results in an increase in expression of Pf4 genes and that cells that cannot produce type IV pili are resistant to infection by Pf4 phage. Our findings suggest that type IV pili are the receptors for Pf4 phage and that the essential activities of MvaT and MvaU are to repress the expression of Pf4 genes.

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Infection of human mucosal tissue by Pseudomonas aeruginosa requires sequential and mutually dependent virulence factors and a novel pilus-associated adhesin

Cited by 105 publications

References 67 publications

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

Type IV Pilin Proteins: Versatile Molecular Modules

Basis for the Essentiality of H-NS Family Members in Pseudomonas aeruginosa

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