Independent Regulation of Type VI Secretion in Vibrio cholerae by TfoX and TfoY

Abstract

SummaryType VI secretion systems (T6SSs) are nanomachines used for interbacterial killing and intoxication of eukaryotes. Although Vibrio cholerae is a model organism for structural studies on T6SSs, the underlying regulatory network is less understood. A recent study showed that the T6SS is part of the natural competence regulon in V. cholerae and is activated by the regulator TfoX. Here, we identify the TfoX homolog TfoY as a second activator of the T6SS. Importantly, despite inducing the same T6SS core machinery, the overall regulons differ significantly for TfoX and TfoY. We show that TfoY does not contribute to competence induction. Instead, TfoY drives the production of T6SS-dependent and T6SS-independent toxins, together with an increased motility phenotype. Hence, we conclude that V. cholerae uses its sole T6SS in response to diverse cues and for distinctive outcomes: either to kill for the prey’s DNA, leading to horizontal gene transfer, or as part of a defensive escape reaction.

Rules of Engagement: The Type VI Secretion System in Vibrio cholerae

“…The recently identified third auxiliary cluster is predicted to encode for one PAAR motif protein (VCA0284) and a unique effector-immunity pair (VCA0285-86) [22,43]. In addition to the promoters found upstream of each operon, internal promoter activity has been identified within the large cluster and auxiliary clusters 1 and 2 that lie just upstream of the immunity genes [41,45]. The transcriptional regulators that drive expression from these internal promoters are not well understood; however it has been hypothesized that they may allow immunity proteins to be constitutively expressed, thus ensuring protection from neighboring kin cells even in the absence of an active T6SS [41].…”

Bacterial type VI secretion system facilitates niche domination

“…It is well established that chitin-degradation products play a key role in the establishment of the V. fischeri-squid symbiosis (16). As chitin-degradation products induce the T6SS in V. cholerae (12,13), it is conceivable that the same holds true for the T6SS1 of V. fischeri. Indeed, chitin-induced T6SS1 production could occur within the chitin-rich mucus matrix that coats the ciliated surface of the squid's light organ, which might foster competitor exclusion upon initial association with the host.…”

“…1), consistent with the fact that many Vibrio species interact with and feed on natural chitinous surfaces. The authors further deciphered a regulatory link between T6SS induction and natural competence for transformation and demonstrated that T6SS-mediated interbacterial competition can be used by V. cholerae to acquire DNA from killed prey, thereby fostering horizontal gene transfer (12,13). These examples highlight the need to move research toward more realistic conditions that mimic the natural habitats of the bacteria under investigation.…”

Whole-Genome Sequences of 26 Vibrio cholerae Isolates

“…In contrast, the majority of environmental, but not clinical, isolates constitutively killed Escherichia coli prey. Because different regulatory schemes control the phenotypes tested (11, 12), we sought to better understand the genetics that underlie these diverse V. cholerae phenotypes by characterizing whole-genome sequences of 23 environmental and three clinical isolates from Bernardy et al…”