title: Vibrio cholerae hemolysin is required for lethality, developmental delay, and intestinal vacuolation in Caenorhabditis elegans.
abstract: BACKGROUND
  Cholera toxin (CT) and toxin-co-regulated pili (TCP) are the major virulence factors of Vibrio cholerae O1 and O139 strains that contribute to the pathogenesis of disease during devastating cholera pandemics. However, CT and TCP negative V. cholerae strains are still able to cause severe diarrheal disease in humans through mechanisms that are not well understood.
  
  
  RESULTS
  To determine the role of other virulence factors in V. cholerae pathogenesis, we used a CT and TCP independent infection model in the nematode Caenorhabditis elegans and identified the hemolysin A (hlyA) gene as a factor responsible for animal death and developmental delay. We demonstrated a correlation between the severity of infection in the nematode and the level of hemolytic activity in the V. cholerae biotypes. At the cellular level, V. cholerae infection induces formation of vacuoles in the intestinal cells in a hlyA dependent manner, consistent with the previous in vitro observations.
  
  
  CONCLUSIONS
  Our data strongly suggest that HlyA is a virulence factor in C. elegans infection leading to lethality and developmental delay presumably through intestinal cytopathic changes.
authors.affiliation: Division of Virulence Assessment, Food and Drug Administration, Laurel, Maryland, USA. hediye.cinar@fda.hhs.gov
authors.forename: Hediye Nese
authors.initials: HN
authors.lastname: Cinar
authors.forename: Mahendra
authors.initials: M
authors.lastname: Kothary
authors.forename: Atin R
authors.initials: AR
authors.lastname: Datta
authors.forename: Ben D
authors.initials: BD
authors.lastname: Tall
authors.forename: Robert
authors.initials: R
authors.lastname: Sprando
authors.forename: Kivanc
authors.initials: K
authors.lastname: Bilecen
authors.forename: Fitnat
authors.initials: F
authors.lastname: Yildiz
authors.forename: Barbara
authors.initials: B
authors.lastname: McCardell
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000382:microbiology*; D006460:Hemolysin Proteins / Q000235:genetics / Q000502:physiology*; D007422:Intestines / Q000382:microbiology*; D014617:Vacuoles / Q000382:microbiology*; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D037521:Virulence Factors; C073845:hemolysin, Vibrio