title: Genetic analysis of Vibrio parahaemolyticus intestinal colonization.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Division of Infectious Diseases, Brigham & Women's Hospital, Boston, MA 02115;
authors.forename: Troy P
authors.initials: TP
authors.lastname: Hubbard
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Division of Infectious Diseases, Brigham & Women's Hospital, Boston, MA 02115;
authors.forename: Michael C
authors.initials: MC
authors.lastname: Chao
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of Norway, 9037 Tromso, Norway; Centre for Molecular Medicine Norway, Nordic EMBL Partnership for Molecular Medicine, 0318 Oslo, Norway;
authors.forename: Sören
authors.initials: S
authors.lastname: Abel
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Division of Infectious Diseases, Brigham & Women's Hospital, Boston, MA 02115;
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Blondel
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of Norway, 9037 Tromso, Norway; Centre for Molecular Medicine Norway, Nordic EMBL Partnership for Molecular Medicine, 0318 Oslo, Norway;
authors.forename: Pia
authors.initials: P
authors.lastname: Abel Zur Wiesch
authors.affiliation: Department of Pathobiology & Veterinary Science, University of Connecticut, Storrs, CT 06269;
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Division of Infectious Diseases, Brigham & Women's Hospital, Boston, MA 02115; Howard Hughes Medical Institute, Boston, MA 02115.
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Division of Infectious Diseases, Brigham & Women's Hospital, Boston, MA 02115; Howard Hughes Medical Institute, Boston, MA 02115 mwaldor@research.bwh.harvard.edu.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000821:virology*; D011817:Rabbits; D014157:Transcription Factors / Q000378:metabolism; D000069296:Type III Secretion Systems; D014735:Vibrio Infections / Q000235:genetics* / Q000821:virology; D014736:Vibrio parahaemolyticus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D014157:Transcription Factors; D000069296:Type III Secretion Systems
keywords: Vibrio parahaemolyticus; bacterial pathogenesis; pathogen evolution; transposon-insertion sequencing; type III secretion