Quorum-sensing- and type VI secretion-mediated spatiotemporal cell death drives genetic diversity in Vibrio cholerae. Author Ameya Mashruwala, Boyang Qin, Bonnie Bassler Publication Year 2022 Type Journal Article Abstract Bacterial colonies composed of genetically identical individuals can diversify to yield variant cells with distinct genotypes. Variant outgrowth manifests as sectors. Here, we show that Type VI secretion system (T6SS)-driven cell death in Vibrio cholerae colonies imposes a selective pressure for the emergence of variant strains that can evade T6SS-mediated killing. T6SS-mediated cell death occurs in two distinct spatiotemporal phases, and each phase is driven by a particular T6SS toxin. The first phase is regulated by quorum sensing and drives sectoring. The second phase does not require the T6SS-injection machinery. Variant V. cholerae strains isolated from colony sectors encode mutated quorum-sensing components that confer growth advantages by suppressing T6SS-killing activity while simultaneously boosting T6SS-killing defenses. Our findings show that the T6SS can eliminate sibling cells, suggesting a role in intra-specific antagonism. We propose that quorum-sensing-controlled T6SS-driven killing promotes V. cholerae genetic diversity, including in natural habitats and during disease. Keywords Gene Expression Regulation, Bacterial, Quorum Sensing, Vibrio cholerae, Bacterial Proteins, Genetic Variation, Type VI Secretion Systems Journal Cell Volume 185 Issue 21 Pages 3966-3979.e13 Date Published 2022 Oct 13 ISSN Number 1097-4172 DOI 10.1016/j.cell.2022.09.003 Alternate Journal Cell PMCID PMC9623500 PMID 36167071 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML