Abstract
Summary Vibrio cholerae isolates responsible for cholera pandemics represent only a small portion of the diverse strains belonging to this species. Indeed, most V. cholerae are encountered in aquatic environments. To better understand the emergence of pandemic lineages, it is crucial to discern what differentiates pandemic strains from their environmental relatives. Here, we studied the interaction of environmental V. cholerae with eukaryotic predators or competing bacteria and tested the contributions of the haemolysin and the type VI secretion system (T6SS) to those interactions. Both of these molecular weapons are constitutively active in environmental isolates but subject to tight regulation in the pandemic clade. We showed that several environmental isolates resist amoebal grazing and that this anti‐grazing defense relies on the strains' T6SS and its actincross‐linking domain (ACD)‐containing tip protein. Strains lacking the ACD were unable to defend themselves against grazing amoebae but maintained high levels of T6SS‐dependent interbacterial killing. We explored the latter phenotype through whole‐genome sequencing of 14 isolates, which unveiled a wide array of novel T6SS effector and (orphan) immunity proteins. By combining these in silico predictions with experimental validations, we showed that highly similar but non‐identical immunity proteins were insufficient to provide cross‐immunity among those wild strains.
Highlights
Diarrheal diseases can be caused by a variety of microorganisms, including the causative agent of cholera, Vibrio cholerae, which infects up to 4 million people every year (Ali et al., 2015)
Another toxic protein that shows differential activity in pandemic compared with nonpandemic V. cholerae strains is the hemolysin protein (HlyA), which is likewise widespread among Vibrio species (Zhang and Austin, 2005)
To better understand the accessory genome, including the T6SS E/I modules and to identify those genes that are novel when compared with strain N16961, we first whole-genome sequenced these strains using a long-read PacBio approach followed by the de novo assembly of their 176 genomes
Summary
Diarrheal diseases can be caused by a variety of microorganisms, including the causative agent of cholera, Vibrio cholerae, which infects up to 4 million people every year (Ali et al., 2015). The aux 3 effector TseH was predicted to contain a hydrolase domain (Altindis et al, 2015), while the recently reported crystal structure supported its role as a papain-like NlpC/P60 peptidase (Hersch et al, 2020) with structural similarity to the T6SS effector Tse of Pseudomonas aeruginosa that contains bacteriolytic peptidoglycan amidase activity (Chou et al, 2012) Another toxic protein that shows differential activity in pandemic compared with nonpandemic V. cholerae strains is the hemolysin protein (HlyA), which is likewise widespread among Vibrio species (Zhang and Austin, 2005). We experimentally tested how the environmental isolates compete with one another and how this interbacterial competition correlates with their T6SS E/I repertoire
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