Diarrhoea from Vibrio parahaemolyticus? It runs in the genes

Vibrio parahaemolyticus is an autochthonous, marine γ-proteobacterium. In the wild, it may exist as either a plankter or in association with marine invertebrates, yet it is most infamous as a facultative human pathogen and as the most common global cause of seafood-induced gastroenteritis. Pathogenic strains of V. parahaemolyticus all possess a multiprotein complex, known as a Type III Secretion System (T3SS2), to directly translocate pathogenic proteins into host cells. The T3SS2 is encoded by horizontally acquired pathogenicity island, which also confers the ability to synthesise a pore-forming haemolysin (TDH). When such enterotoxic strains are introduced into the mammalian digestive track, they can multiply rapidly and induce nausea, diarrhoea and abdominal cramps. Therefore, understanding the pathogenesis of V. parahaemolyticus has implications to public health and in developing an effective treatment.

Genome analysis and the establishment of mammalian model systems has confidently identified the role of T3SS2 in pathogenesis, but other factors that contribute to the virulence of pathogenic strains are poorly understood. Therefore, Troy Hubbard and colleagues (2016) employed transposon-insertion sequencing to screen for genetic elements that may play a contributory role in the viability of V. parahaemolyticus O3:K6 in mammalian intestines. Phenotypic examination of insertion mutants from both in vitro culture and in vivo infection of infant rabbits allowed the authors to screen for genes involved in bacterial virulence. Subsequent analysis identified 565 genes that likely contribute to pathogenesis and intestinal colonisation in this species, many of which have previously not been attributed in host invasion in this bacterium (such as lipopolysaccharide and nucleotide synthesis) and others which are V. parahaemolyticus-specific.

Most strikingly of all was the discovery that toxR is integral to virulence and necessary in T3SS2 gene expression. ToxR is a transmembrane transcription factor ancestral in the Vibrio genus and is most widely recognised for its role in regulating a virulence cascade involving horizontally-acquired pathogenic elements in V. chloerae. While this may not seem surprising (as ToxR is responsive to intestinal stimuli), this noteworthy discovery suggests that two pathogenic vibrios independently linked the regulation of the ancestral toxR gene to two distinct, horizontally-acquired mechanisms of infection.

Overall, this study provides a thorough and comprehensive genetic analysis of intestinal colonization and pathogenesis in V. parahaemolyticus O3:K6. The identification of T3SS2-independent genes associated with infection provides a more holistic understanding to pathogenesis in this species and may aid in developing an effective treatment. I am most excited, however, about the insights provided into the virulent role of toxR regulation. Having developed convergently, I am now curious as to how prevalent this phenomenon is in other pathogenic vibrios. For example, is a similar mechanism employed by pathogens of marine molluscs (such as Vibrio splendidus) or is it only employed by those that infect mammalian hosts? While speculative at this stage, exciting findings such as these that link pathogenesis across the vibrios could contribute to a pan-Vibrio treatment to common diseases, should such a panacea be possible. Nevertheless, this paper makes a positive step forward in our understanding of a common pathogen in marine systems and may lead to a shift in our thinking as to how pathogenesis is regulated across this prevalent clade. 

Reviewed Paper: Hubbard, T. P., Chao, M. C., Abel, S., Blondel, C. J., zur Wiesch, P. A., Zhou, X., ... & Waldor, M. K. (2016). Genetic analysis of Vibrio parahaemolyticus intestinal colonization. Proceedings of the National Academy of Sciences, 113(22), 6283-6288. http://www.pnas.org/content/113/22/6283.short