vibrio cholerae hemolysin is required for lethality, developmental delay, and intestinal vacuolation in caenorhabditis elegans霍乱弧菌溶血素需要杀伤力,发育迟缓,肠道线虫的空泡形成.pdfVIP

Vibrio cholerae Hemolysin Is Required for Lethality, Developmental Delay, and Intestinal Vacuolation in Caenorhabditis elegans 1 1 1 1 3 2 Hediye Nese Cinar *, Mahendra Kothary , Atin R. Datta , Ben D. Tall , Robert Sprando , Kivanc Bilecen , Fitnat Yildiz2, Barbara McCardell1 1 Division of Virulence Assessment, Food and Drug Administration, Laurel, Maryland, United States of America, 2 Department of Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, United States of America, 3 Division of Toxicology, Food and Drug Administration, Laurel, Maryland, United States of America 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. Methodology/Principal Findings: 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/Significance: Our data strongly suggest that HlyA is a virulence factor in C. elegans infection lead