Pseudomonas aeruginosa Pili and Flagella Mediate Distinct Binding and Signaling Events at the Apical and Basolateral Surface of Airway Epithelium

Bucior, Iwona; Pielage, Julia F.; Engel, Joanne N.

doi:10.1371/journal.ppat.1002616

Cited by 159 publications

(150 citation statements)

References 62 publications

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“…However, in natural environments such as the mucosal epithelia of their hosts, bacteria would freely transition from swimming (planktonic) to surface-attached states (16). In an effort to establish the importance of surface mechanosensing in a more realistic environment, we measured the activity of the PaQa reporter in the presence of mucin, a major component of mucus, in a semiinfinite liquid environment where cells are free to attach or swim away from the surface.…”

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.

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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.

Self Cite

343

398

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“…Resistance to phages due to modified type IV pili has consequences for bacterial motility by affecting twitching -a form of solid surface translocation (Chiang & Burrows, 2003). Type IV pili allow the adherence of P. aeruginosa cells to the host epithelium and also play a role in biofilm formation (Bucior et al, 2012;Klausen et al, 2003;O'Toole & Kolter, 1998). The mechanism of resistance associated with the loss of pili may drive an increase in P. aeruginosa diversity and strongly reduce infectivity…”

Section: Introductionmentioning

confidence: 99%

Pseudolysogeny and sequential mutations build multiresistance to virulent bacteriophages in Pseudomonas aeruginosa

Latino

2016

Microbiology

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Coevolution between bacteriophages (phages) and their prey is the result of mutualistic interactions. Here, we show that pseudolysogeny is a frequent outcome of infection by virulent phages of Pseudomonas aeruginosa and that selection of resistant bacterial mutants is favoured by continuous production of phages. We investigated the frequency and characteristics of P. aeruginosa strain PAO1 variants resisting infection by different combinations of virulent phages belonging to four genera. The frequency of resistant bacteria was 10 25 for single phage infection and 10 26 for infections with combinations of two or four phages. The genome of 27 variants was sequenced and the comparison with the genome of the parental PAO1 strain allowed the identification of point mutations or small indels. Four additional variants were characterized by a candidate gene approach. In total, 27 independent mutations were observed affecting 14 genes and a regulatory region. The mutations affected genes involved in biosynthesis of type IV pilus, alginate, LPS and O-antigen. Half of the variants possessed changes in homopolymer tracts responsible for frameshift mutations and these phase variation mutants were shown to be unstable. Eleven double mutants were detected. The presence of free phage DNA was observed in association with exclusion of superinfection in half of the variants and no chromosomal mutation could be found in three of them. Upon further growth of these pseudolysogens, some variants with new chromosomal mutations were recovered, presumably due to continuous evolutionary pressure.

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“…Flagella have been shown to play a significant role in the colonization of host tissues by a wide variety of bacteria (26)(27)(28)(29)(30). Flagella and motility have been implicated in the ability of C. difficile to cause disease in animal models, but there are conflicting data on the exact way in which flagella impact virulence.…”

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confidence: 99%

The Second Messenger Cyclic Di-GMP Regulates Clostridium difficile Toxin Production by Controlling Expression of sigD

et al. 2013

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The Gram-positive obligate anaerobe Clostridium difficile causes potentially fatal intestinal diseases. How this organism regulates virulence gene expression is poorly understood. In many bacterial species, the second messenger cyclic di-GMP (c-di-GMP) negatively regulates flagellar motility and, in some cases, virulence. c-di-GMP was previously shown to repress motility of C. difficile. Recent evidence indicates that flagellar gene expression is tightly linked with expression of the genes encoding the two C. difficile toxins TcdA and TcdB, which are key virulence factors for this pathogen. Here, the effect of c-di-GMP on expression of the toxin genes tcdA and tcdB was determined, and the mechanism connecting flagellar and toxin gene expressions was examined. In C. difficile, increasing c-di-GMP levels reduced the expression levels of tcdA and tcdB, as well as that of tcdR, which encodes an alternative sigma factor that activates tcdA and tcdB expression. We hypothesized that the C. difficile orthologue of the flagellar alternative sigma factor SigD (FliA; 28 ) mediates regulation of toxin gene expression in response to c-di-GMP. Indeed, ectopic expression of sigD in C. difficile resulted in increased expression levels of tcdR, tcdA, and tcdB. Furthermore, sigD expression enhanced toxin production and increased the cytopathic effect of C. difficile on cultured fibroblasts. Finally, evidence is provided that SigD directly activates tcdR expression and that SigD cannot activate tcdA or tcdB expression independent of TcdR. Taken together, these data suggest that SigD positively regulates toxin genes in C. difficile and that c-di-GMP can inhibit both motility and toxin production via SigD, making this signaling molecule a key virulence gene regulator in C. difficile.

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Pseudomonas aeruginosa Pili and Flagella Mediate Distinct Binding and Signaling Events at the Apical and Basolateral Surface of Airway Epithelium

Cited by 159 publications

References 62 publications

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

Pseudolysogeny and sequential mutations build multiresistance to virulent bacteriophages in Pseudomonas aeruginosa

The Second Messenger Cyclic Di-GMP Regulates Clostridium difficile Toxin Production by Controlling Expression of sigD

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