Evolution of a
            <i>cis</i>
            -Acting SNP That Controls Type VI Secretion in Vibrio cholerae

Ng, Siu Lung; Kammann, Sophia; Steinbach, Gabi; Hoffmann, Tobias; Yunker, Peter; Hammer, Brian K.

doi:10.1128/mbio.00422-22

Cited by 8 publications

(7 citation statements)

References 68 publications

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“…Importantly, for several phenotypes, an increased fitness has been demonstrated for heterogenous populations, supporting the idea that bacteria can use bet-hedging strategies to maximize survival [67]. Notably, the observed sporadic (or stochastic) VxrAB-dependent T6SS production phenotype differed significantly from the T6SS status of environmental and non-pandemic V. cholerae strains, which contain a deterministic SNP upstream of vipA [36,37]. Indeed, strains carrying this SNP, as well as TfoX-/TfoY-producing 7PET strains, show almost uniform T6SS production within the population consistent with increased T6SS transcript levels compared to those in WT 7PET strains, as demonstrated previously through RNA sequencing (RNA-seq) [24,28,36].…”

Section: Discussionmentioning

confidence: 67%

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Sporadic type VI secretion in seventh pandemic Vibrio cholerae

et al. 2023

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Vibrio cholerae is a pathogen that causes disease in millions of people every year by colonizing the small intestine and then secreting the potent cholera toxin. How the pathogen overcomes the colonization barrier created by the host’s natural microbiota is, however, still not well understood. In this context, the type VI secretion system (T6SS) has gained considerable attention given its ability to mediate interbacterial killing. Interestingly, and in contrast to non-pandemic or environmental V. cholerae isolates, strains that are causing the ongoing cholera pandemic (7PET clade) are considered T6SS-silent under laboratory conditions. Since this idea was recently challenged, we performed a comparative in vitro study on T6SS activity using diverse strains or regulatory mutants. We show that modest T6SS activity is detectable in most of the tested strains under interbacterial competition conditions. The system’s activity was also observed through immunodetection of the T6SS tube protein Hcp in culture supernatants, a phenotype that can be masked by the strains’ haemagglutinin/protease. We further investigated the low T6SS activity within the bacterial populations by imaging 7PET V. cholerae at the single-cell level. The micrographs showed the production of the machinery in only a small fraction of cells within the population. This sporadic T6SS production was higher at 30 °C than at 37 °C and occurred independently of the known regulators TfoX and TfoY but was dependent on the VxrAB two-component system. Overall, our work provides new insight into the heterogeneity of T6SS production in populations of 7PET V. cholerae strains in vitro and provides a possible explanation of the system’s low activity in bulk measurements.

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Section: Discussionmentioning

confidence: 67%

“…In this context, we recently reported the experimental identification of a single-nucleotide polymorphism (SNP) located in an intergenic region within the primary T6SS cluster of V. cholerae [36], which was concomitantly also identified by others using a bioinformatic approach [37]. We demonstrated that the exchange of this SNP (e.g.…”

Section: Introductionmentioning

confidence: 95%

Sporadic type VI secretion in seventh pandemic Vibrio cholerae

et al. 2023

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“…All V. cholerae mutant strains were made using the pKAS allelic exchange system described by Skorupski et al using pKAS32 (Skorupski & Taylor, 1996). JT101 and SN598 (Table S1) were described in previous studies (Ng et al, 2022;Thomas et al, 2017). CZ005 and CZ006 were generated through an insertion of a spectinomycin resistance cassette into the lacZ gene of JT101 and SN598, respectively.…”

Section: Mutant Constructionmentioning

confidence: 99%

Constitutive expression of the Type VI Secretion System carries no measurable fitness cost in Vibrio cholerae

Zhang,

Datta,

Ratcliff

et al. 2024

Ecology and Evolution

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The Type VI Secretion System (T6SS) is a widespread and highly effective mechanism of microbial warfare; it confers the ability to efficiently kill susceptible cells within close proximity. Due to its large physical size, complexity, and ballistic basis for intoxication, it has widely been assumed to incur significant growth costs in the absence of improved competitive outcomes. In this study, we precisely examine the fitness costs of constitutive T6SS firing in the bacterium Vibrio cholerae. We find that, contrary to expectations, constitutive expression of the T6SS has a negligible impact on growth, reducing growth fitness by 0.025 ± 0.5% (95% CI) relative to a T6SS− control. Mathematical modeling of microbial populations demonstrates that, due to clonal interference, constitutive expression of the T6SS will often be neutral, with little impact on evolutionary outcomes. Our findings underscore the importance of precisely measuring the fitness costs of microbial social behaviors and help explain the prevalence of the T6SS across Gram‐negative bacteria.

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“…In the current pandemic strains of V. cholerae , this activation is orchestrated by the TfoX master regulator once the bacteria reach a high cell density state [42,43,45,46]. In environmental V. cholerae isolates, the T6SS machinery is in a state of constant activity [20,47–50], representing an immediate risk for T6SS-associated harm in case cell-to-cell contact in established. Therefore, bacteria must distinguish between nearby individuals before intentionally initiating cell-to-cell contact.…”

Section: Introductionmentioning

confidence: 99%

Interactions between pili affect the outcome of bacterial competition driven by the type VI secretion system

Otto,

Servajean,

Lemopoulos

et al. 2023

Preprint

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The bacterial type VI secretion system (T6SS) is a widespread, kin-discriminatory weapon capable of shaping microbial communities. Due to the system's dependency on contact, cellular interactions can lead to either competition or kin protection. Cell-to-cell contact is often accomplished via surface-exposed type IV pili (T4P). In Vibrio cholerae, these T4P facilitate specific interactions when the bacteria colonize natural chitinous surfaces. However, it has remained unclear whether and, if so, how these interactions affect the bacterium's T6SS-mediated killing. In this study, we demonstrate that pilus-mediated interactions can be harnessed to reduce the population of V. cholerae under liquid growth conditions in a T6SS-dependent manner. We also show that the naturally occurring diversity of pili determines the likelihood of cell-to-cell contact and, consequently, the extent of T6SS-mediated competition. To determine the factors that enable or hinder the T6SS's targeted reduction of competitors carrying pili, we developed a physics-grounded computational model for autoaggregation. Collectively, our research demonstrates that T4P involved in cell-to-cell contact can impose a selective burden when V. cholerae encounters non-kin cells that possess an active T6SS. Additionally, our study underscores the significance of T4P diversity in protecting closely related individuals from T6SS attacks through autoaggregation and spatial segregation.

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Evolution of a cis -Acting SNP That Controls Type VI Secretion in Vibrio cholerae

Cited by 8 publications

References 68 publications

Sporadic type VI secretion in seventh pandemic Vibrio cholerae

Sporadic type VI secretion in seventh pandemic Vibrio cholerae

Constitutive expression of the Type VI Secretion System carries no measurable fitness cost in Vibrio cholerae

Interactions between pili affect the outcome of bacterial competition driven by the type VI secretion system

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