Vibrio type III secretion system 2 is not restricted to the Vibrionaceae and encodes differentially distributed repertoires of effector proteins

Abstract

<i>Vibrio parahaemolyticus</i> is the leading cause of seafood-borne gastroenteritis worldwide. A distinctive feature of the O3:K6 pandemic clone, and its derivatives, is the presence of a second, phylogenetically distinct, type III secretion system (T3SS2) encoded within the genomic island VPaI-7. The T3SS2 allows the delivery of effector proteins directly into the cytosol of infected eukaryotic cells to subvert key host-cell processes, critical for <i>V. parahaemolyticus</i> to colonize and cause disease. Furthermore, the T3SS2 also increases the environmental fitness of <i>V. parahaemolyticus</i> in its interaction with bacterivorous protists; hence, it has been proposed that it contributed to the global oceanic spread of the pandemic clone. Several reports have identified T3SS2-related genes in <i>Vibrio</i> and non-<i>Vibrio</i> species, suggesting that the T3SS2 gene cluster is not restricted to the <i>Vibrionaceae</i> and can mobilize through horizontal gene transfer events. In this work, we performed a large-scale genomic analysis to determine the phylogenetic distribution of the T3SS2 gene cluster and its repertoire of effector proteins. We identified putative T3SS2 gene clusters in 1130 bacterial genomes from 8 bacterial genera, 5 bacterial families and 47 bacterial species. A hierarchical clustering analysis allowed us to define six T3SS2 subgroups (I-VI) with different repertoires of effector proteins, redefining the concepts of T3SS2 core and accessory effector proteins. Finally, we identified a subset of the T3SS2 gene clusters (subgroup VI) that lacks most T3SS2 effector proteins described to date and provided a list of 10 novel effector candidates for this subgroup through bioinformatic analysis. Collectively, our findings indicate that the T3SS2 extends beyond the family <i>Vibrionaceae</i> and suggest that different effector protein repertories could have a differential impact on the pathogenic potential and environmental fitness of each bacterium that has acquired the <i>Vibrio</i> T3SS2 gene cluster.