When the pandemic opts for the lockdown: Secretion system evolution in the cholera bacterium

Vibrio cholerae, the causative agent of the diarrheal disease cholera, is a microbe capable of inhabiting two different ecosystems: chitinous surfaces in brackish, estuarine waters and the epithelial lining of the human gastrointestinal tract. V. cholerae defends against competitive microorganisms with a contact-dependent, contractile killing machine called the type VI secretion system (T6SS) in each of these niches. The T6SS resembles an inverted T4 bacteriophage tail and is used to deliver toxic effector proteins into neighboring cells. Pandemic strains of V. cholerae encode a unique set of T6SS effector proteins, which may play a role in pathogenesis or pandemic spread. In our recent study (Santoriello et al. (2020), Nat Commun, doi: 10.1038/s41467-020-20012-7), using genomic and molecular biology tools, we demonstrated that the T6SS island Auxiliary Cluster 3 (Aux3) is unique to pandemic strains of V. cholerae. We went on to show that Aux3 is related to a phage-like element circulating in environmental V. cholerae strains and that two genetic domestication events formed the pandemic Aux3 cluster during the evolution of the pandemic clone. Our findings support two main conclusions: (1) Aux3 evolution from phage-like element to T6SS cluster offers a snapshot of phage domestication in early T6SS evolution and (2) chromosomal maintenance of Aux3 was advantageous to the common ancestor of V. cholerae pandemic strains.