Effect of chemotaxis on the interaction of cholera vibrios with intestinal mucosa

Freter, Rolf; O’Brien, Patrícia C. M.; Mácsai, Mónika

doi:10.1093/ajcn/32.1.128

Cited by 81 publications

(70 citation statements)

References 5 publications

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“…Early work by Freter et al (6,10) proposed that the ability of nonchemotactic V. cholerae to out-compete wild-type was a result of an inability of the former to enter the intestinal crypts. It was proposed that a large percentage of wild-type V. cholerae are killed by innate immune defenses within the crypts and that the out-competition of nonchemotactic V. cholerae is a direct result of avoiding such killing.…”

Section: Ccw-biased Rotation Results In Increased Infectivitymentioning

confidence: 99%

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Both chemotaxis and net motility greatly influence the infectivity of Vibrio cholerae

Butler

Camilli

2004

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

184

206

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The role of chemotaxis in the virulence of gastrointestinal pathogens is ill defined. Counterintuitively, nonchemotactic mutants of the polarly flagellated pathogen Vibrio cholerae greatly outcompete the wild-type strain during infection of the small intestine. We show that the out-competition phenotype is dependent on the direction of flagellar rotation and independent of Toxin Co-regulated Pilus function. Specifically, the out-competition associated with the loss of chemotaxis required the presence of counterclockwise-biased flagellar rotation and smooth straight runs by the bacteria. In contrast, a nonchemotactic strain with clockwise-biased flagellar rotation was confined to small-scale net movement and was attenuated for infection. The significance of the out-competition phenotype was examined and was shown to correlate with a true increase in infectivity. Counterclockwisebiased mutants are aberrantly distributed throughout the infant mouse small intestine and we find that the expression of virulence factors occurs normally in all segments. Thus, alteration of the chemotactic properties of V. cholerae allows it to exploit additional niches in the host intestine.T he Gram-negative bacterium Vibrio cholerae is the causative agent of the epidemic disease cholera. Cholera patients are afflicted with a profuse watery diarrhea resulting from the action of the ADP-ribosylating cholera toxin (CT). This organism is highly motile by means of a single polar sheathed flagellum and is believed to use the processes of motility and chemotaxis to travel from the lumen of the small intestine to its preferred intestinal niche on the intestinal epithelium. In this niche V. cholerae expresses a number of virulence factors including CT and the toxin co-regulated type IV pilus (TCP). The latter has been shown to be essential for colonization of humans (1), as well as in the infant mouse model of infection (2).Within the V. cholerae genome are multiple paralogues of chemotaxis genes (3). Despite the presence of three chemotaxis operons, only one of these operons is required for chemotaxis (4). The function of the remaining chemotaxis operons remains unknown. Chemotaxis in many organisms is achieved by modulating change in the direction of flagellar rotation from the default direction of counterclockwise (CCW) to clockwise (CW) rotation. In the peritrichously flagellated bacterium Escherichia coli, CCW rotation results in the bacterium swimming smoothly in a mostly straight line, whereas CW rotation causes the cell to turn abruptly in a process known as tumbling (5). Because of the presence of a single polar flagellum, V. cholerae does not tumble per se but instead reverses direction brief ly, thereby allowing the bacterium to randomly reorient itself and swim in a new direction.Although motility and chemotaxis are believed to guide V. cholerae to its preferred colonization site within the small intestine, the precise role of each of these processes during infection has not been clearly established. Previous work by Freter et al. ...

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Section: Ccw-biased Rotation Results In Increased Infectivitymentioning

confidence: 99%

“…Previous work by Freter et al (6) revealed that motility is required for the establishment of an infection. However, subsequent work by two other groups indicated that motility might in fact be dispensable for infection (7,8).…”

mentioning

confidence: 99%

Both chemotaxis and net motility greatly influence the infectivity of Vibrio cholerae

Butler

Camilli

2004

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

184

206

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“…were enumerated on LB and on selective medium (LB with mecillinam for rcsC constitutive mutants). A competitive index (CI) for each mutant was calculated as the ratio between the mutant and the wild-type strain in the output (bacteria recovered from the host after infection) divided by their ratio in the input (initial inoculum) (Beuzó n & Holden, 2001;Freter et al, 1981;Taylor et al, 1987).…”

Section: Methodsmentioning

confidence: 99%

Virulence attenuation in Salmonella enterica rcsC mutants with constitutive activation of the Rcs system

et al. 2005

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Mutations in rcsC that result in constitutive colanic acid capsule synthesis were obtained in Salmonella enterica serovar Typhimurium. Most rcsC alleles were dominant; however, recessive rcsC alleles were also found, in agreement with the postulated double role (positive and negative) of RcsC on the activation of the RcsB/C phosphorelay system. Salmonella rcsC mutants with constitutive activation of the Rcs system are severely attenuated for virulence in BALB/c mice and their degree of attenuation correlates with the level of Rcs activation. Partial relief of attenuation by a gmm mutation indicates that capsule overproduction is one of the factors leading to avirulence in constitutively activated rcsC mutants. INTRODUCTIONThe Rcs phosphorelay system was initially characterized in Escherichia coli as a two-component positive regulator of colanic acid capsule synthesis encoded by rcsC and rcsB (Brill et al., 1988;Gottesman et al., 1985;Stout & Gottesman, 1990). The sensor protein RcsC, a hybrid histidine kinase, and the transcriptional activator RcsB are the main components of the system, which also includes a second transcriptional activator, RcsA (Stout et al., 1991) and an intermediate phosphotransmitter, YojN (Takeda et al., 2001). The Rcs system is also a negative regulator of the flagellar master operon flhDC (Francez-Charlot et al., 2003), whose products are necessary for the expression of genes involved in flagellum synthesis, motility and chemotaxis.The first environmental signal shown to strongly and rapidly induce colanic acid synthesis was osmotic upshift (Sledjeski & Gottesman, 1996). This effect was mediated by the Rcs system. More recently it has been shown that the Rcs phosphorelay can be activated when wild-type cells are grown at 20 uC in the presence of glucose and a high concentration of Zn 2+ (Hagiwara et al., 2003). Furthermore, several genetic conditions that result in alterations in envelope composition or integrity are known to activate the Rcs system. For example, a mutation in the mdoH gene involved in the biosynthesis of membrane-derived oligosaccharides (Ebel et al., 1997) Here, we describe the isolation of Salmonella rcsC mutants with constitutive activation of the Rcs system, and the characterization of amino acid substitutions that lead to different degrees of activation of the system. Virulence trials with constitutively activated rcsC mutants provide a direct demonstration of the link between activation of the Rcs system and avirulence in mice. We also show that virulence attenuation associated with activation of the RcsB/C system is partially due to colanic acid overproduction. METHODSBacterial strains, bacteriophages and strain construction.S. enterica serovar Typhimurium strains used in this study are described in Table 1. Unless otherwise indicated, the strains derive from the mouse-virulent strain 14028. Transductional crosses using phage P22 HT 105/1 int201 (Schmieger, 1972) were used for strain construction operations. The transduction protocol was described by Maloy (199...

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“…The presence of this organism in aquatic environments contributes to endemic disease, and the evolution of new pathogenic strains provides the potential for epidemic, and even pandemic, spread (Mel and Mekalanos, 1996). The relationship between V. cholerae motility and pathogenesis has been studied for many years (Fretter et al, 1981); however, a well-defined role for motility in this context still remains uncertain (Richardson, 1991;Gardel and Mekalanos, 1996). Some interesting links between the expression of virulence determinants and motility have been found recently.…”

Section: Glowing Squid Septic Trout and Aquatic Vibriosmentioning

confidence: 99%

Roles for motility in bacterial–host interactions

Ottemann

Miller

1997

Molecular Microbiology

291

217

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SummaryThe ability to move in a directed manner may confer distinct advantages upon host-adapted prokaryotes. Potential benefits of motility include increased efficiency of nutrient acquisition, avoidance of toxic substances, the ability to translocate to preferred hosts and access optimal colonization sites within them, and dispersal in the environment during the course of transmission. The costs of motility also may be significant. These include the metabolic burden of synthesizing flagellar components, the energetic expense of fuelling flagellar motors and the presentation of polymeric and highly antigenic targets to the immune system. It is therefore not surprising that synthesis of the motility apparatus is usually subject to strict control. Studies of a variety of bacterial-host interactions demonstrate roles for motility, and its regulation, at points throughout the infectious cycle.

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Effect of chemotaxis on the interaction of cholera vibrios with intestinal mucosa

Cited by 81 publications

References 5 publications

Both chemotaxis and net motility greatly influence the infectivity of Vibrio cholerae

Both chemotaxis and net motility greatly influence the infectivity of Vibrio cholerae

Virulence attenuation in Salmonella enterica rcsC mutants with constitutive activation of the Rcs system

Roles for motility in bacterial–host interactions

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