Cholera's weapon has more than one trigger

Cholera is caused by the bacterium Vibrio cholerae, which infects the small intestine, causing diarrhea and severe dehydration. The bacterium lives in water, e.g. the sea, where it attaches onto small crustaceans and feeds on a sugar polymer called chitin. In this environment, V. cholerae aggressively steals DNA from neighboring bacteria by stabbing them with a tiny, spring-loaded spear. This is called the “type VI secretion system” (T6SS), and it helps V. cholerae to evolve. EPFL scientists have now discovered that the T6SS is activated by diverse environmental cues. Published in Cell Reports, the new insight could help explain how the pathogen protects itself against predators and, potentially also, against human defense mechanisms.

The structure of the T6SS has been extensively studied in V. cholerae, but this killing nanomachine is found across many species of bacteria, especially Gram-negative ones. In the cholera bacterium it is activated by a regulator protein called TfoX, which the bacterium produces when it encounters two environmental cues: high population density and the polysaccharide chitin.

The lab of Melanie Blokesch at EPFL has now found that the T6SS can also be induced by another regulator, TfoY, which is found in all members of the genus Vibrio. Notably, both TfoX and TfoY have similar protein domains that are widely distributed among many different bacteria. Based on this abundance, the researchers investigated the presence and function of TfoY in V. cholerae.

Using various techniques including RNA sequencing and live-cell microscopy imaging, Blokesch’s lab was able to explore how TfoY contributes to the T6SS induction in V. cholerae, as well as to related phenotypes, e.g. bacterial motility.

The results show that the T6SS of V. cholerae is activated independently by both TfoX and TfoY, but each regulator initiates a distinctive cell fate. In fact, unlike TfoX activation of T6SS, chitin and cell-growth density do not seem to have any bearing on the activity of TfoY. Importantly, TfoY not only induced T6SS in the V. cholerae strains involved in the current 7^th cholera pandemic, but also in non-pandemic isolates of the bacterium.

The authors conclude that V. cholerae uses its T6SS as a “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.”

The findings of this study are expected to extend our knowledge on the ongoing global cholera pandemic based on the successful defense strategies used by this important pathogen.

This work was funded by the Swiss National Science Foundation and the European Research Council.

Reference

Metzger LC, Stutzmann S, Scrignari T, Van der Henst C, Matthey N, Blokesch M. Independent Regulation of Type VI Secretion in Vibrio cholera by TfoX and TfoY. Cell Reports 21 April 2016. DOI: 10.1016/j.celrep.2016.03.092