Modular small RNA drives the emergence of virulence traits and environmental trade-offs in Vibrio cholerae

The molecular drivers and health trade-offs controlling the transition of environmental micro organism into human pathogens stay enigmatic. Here, we describe a small RNA (sRNA) with a novel modular construction that shapes the evolution of toxigenic Vibrio cholerae, the agent of cholera. The sRNA contains a variable 5’ module positioned inside the ompU ORF and a conserved 3’ area downstream. This atypical location confers a definite bimodular construction to the OmpU-encoded sRNA (OueS), producing allelic variants with distinctive capabilities. Unlike environmental counterparts, the OueS allele from toxigenic strains controls phenotypes important throughout host colonization in a domain-dependent method: a) inhibits biofilm formation by suppressing RyhB, b) confers resistance in opposition to intestinal bacteriophages by activating the CBASS system, and c) drives mucus penetration. Toxigenic OueS is crucial for profitable intestinal colonization and acts as a practical surrogate of the grasp virulence regulator ToxR, controlling over 84% of its regulome. However, this allele results in lowered aggressive health throughout colonization of pure reservoirs when in comparison with environmental ones. Finally, we decided that the acquisition of the ompU ORF is modular and managed by exogenous situations, offering vital insights into the evolution of toxigenic V. cholerae and the emergence of pathogenic traits in micro organism.