Genetic analysis of Vibrio parahaemolyticus intestinal colonization

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 22; pp. 6283 - 6288
• Main Authors: Hubbard, Troy P., Chao, Michael C., Abel, Sören, Blondel, Carlos J., Wiesch, Pia Abel zur, Zhou, Xiaohui, Davis, Brigid M., Waldor, Matthew K.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 31.05.2016
• Subjects: Animals; Aquaculture; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological Sciences; DNA, Bacterial - genetics; Gene expression; Gene Expression Regulation, Bacterial; Genes; Genetic Testing - methods; Humans; Intestines - metabolism; Intestines - virology; Pathogens; Rabbits; Transcription Factors - metabolism; Type III Secretion Systems; Vibrio cholerae; Vibrio Infections - genetics; Vibrio Infections - virology; Vibrio parahaemolyticus; Vibrio parahaemolyticus - genetics; Vibrio parahaemolyticus - metabolism; Vibrio parahaemolyticus - pathogenicity; Virulence - genetics; Vibrio parahaemolyticus; bacterial pathogenesis; transposon-insertion sequencing; pathogen evolution; type III secretion
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1601718113

Vibrio parahaemolyticus is the most common cause of seafood-borne gastroenteritis worldwide and a blight on global aquaculture. This organism requires a horizontally acquired type III secretion system (T3SS2) to infect the small intestine, but knowledge of additional factors that underlie V. parahaemolyticus pathogenicity is limited. We used transposon-insertion sequencing to screen for genes that contribute to viability of V. parahaemolyticus in vitro and in the mammalian intestine. Our analysis enumerated and controlled for the host infection bottleneck, enabling robust assessment of genetic contributions to in vivo fitness. We identified genes that contribute to V. parahaemolyticus colonization of the intestine independent of known virulence mechanisms in addition to uncharacterized components of T3SS2. Our study revealed that toxR, an ancestral locus in Vibrio species, is required for V. parahaemolyticus fitness in vivo and for induction of T3SS2 gene expression. The regulatory mechanism by which V. parahaemolyticus ToxR activates expression of T3SS2 resembles Vibrio cholerae ToxR regulation of distinct virulence elements acquired via lateral gene transfer. Thus, disparate horizontally acquired virulence systems have been placed under the control of this ancestral transcription factor across independently evolved human pathogens.