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Vibrio cholerae is a diverse species that inhabits a wide range of environments from copepods in brackish waterto the intestines of humans. In order to remain competitive, V. cholerae uses the versatile type-VI secretion system (T6SS) tosecrete anti-prokaryotic and anti-eukaryotic effectors. In addition to competing with other bacterial species, V. cholerae strainsalso compete with one another. Some strains are able to coexist, and are referred to as belonging to the same compatibility group.Challenged by diverse competitors in various environments, different V. choleare strains secrete different combination of effectors– presumably to best suit their niche. Interestingly, all pandemic V. cholerae strains encode the same three effectors. In additionto the diversity displayed in the encoded effectors, the regulation of V. cholerae also differs between strains. Two main layersof regulation appear to exist. One strategy connects T6SS activity with behavior that is suited to fighting eukaryotic cells, whilethe other is linked with natural competence – the ability of the bacterium to acquire and incorporate extracellular DNA. Thisrelationship between bacterial killing and natural competence is potentially a source of diversification for V. cholerae as it hasbeen shown to incorporate the DNA of cells recently killed through T6SS activity. It is through this process that we hypothesizethe transfer of virulence factors, including T6SS effector modules, to happen. Switching of T6SS effectors has the potential tochange the range of competitors V. cholerae can kill and to newly define which strains V. cholerae can co-exist with, two importantparameters for survival in diverse environments.

The type VI secretion system (T6SS) mediates protein translocation across the cell membrane of Gram-negative bacteria, including Vibrio cholerae – the causative agent of cholera. All V. cholerae strains examined to date harbor gene clusters encoding a T6SS. Structural similarity and sequence homology between components of the T6SS and the T4 bacteriophage cell-puncturing device suggest that the T6SS functions as a contractile molecular syringe to inject effector molecules into prokaryotic and eukaryotic target cells. Regulation of the T6SS is critical. A subset of V. cholerae strains, including the clinical O37 serogroup strain V52, express T6SS constitutively. In contrast, pandemic strains impose tight control that can be genetically disrupted: mutations in the quorum sensing gene luxO and the newly described regulator gene tsrA lead to constitutive T6SS expression in the El Tor strain C6706. In this report, we examined environmental V. cholerae isolates from the Rio Grande with regard to T6SS regulation. Rough V. cholerae lacking O-antigen carried a nonsense mutation in the gene encoding the global T6SS regulator VasH and did not display virulent behavior towards Escherichia coli and other environmental bacteria. In contrast, smooth V. cholerae strains engaged constitutively in type VI-mediated secretion and displayed virulence towards prokaryotes (E. coli and other environmental bacteria) and a eukaryote (the social amoeba Dictyostelium discoideum). Furthermore, smooth V. cholerae strains were able to outcompete each other in a T6SS-dependent manner. The work presented here suggests that constitutive T6SS expression provides V. cholerae with an advantage in intraspecific and interspecific competition., Canadian Institutes of Health Research (Operating Grant MOP-84473), Alberta Heritage Foundation for Medical Research (Alberta Innovates-Health Solutions, Endowment Fund), National Institutes of Health (U.S.) (grant MD001091-01), National Institutes of Health (U.S.) (grant GM068855-02), Olegario V. Rana Fellowship, Alberta Heritage Foundation for Medical Research (Alberta Innovates-Health Solutions Graduate Studentships)