Vibrio cholerae Infection of Drosophila melanogaster Mimics the Human Disease Cholera

PLoS Pathogens

Nathan S Blow¹  Paula I Watnick¹  F. Rob Jackson²  Robert N Salomon³  Isabelle Reveillaud⁴  Kerry Garrity⁴  Alan Kopin⁴ 

[1] Department of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Boston, Massachusetts, United States of America;Department of Neurosciences, Tufts University School of Medicine, Boston, Massachusetts, United States of America;Department of Pathology, Tufts-New England Medical Center, Boston, Massachusetts, United States of America;Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, Massachusetts, United States of America

关键词: Vibrio cholerae;    Cholera;    Toxins;    Drosophila melanogaster;    Gastrointestinal tract;    Ingestion;    Virulence factors;    Arthropoda;   

DOI  :  10.1371/journal.ppat.0010008

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Cholera, the pandemic diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, continues to be a major public health challenge in the developing world. Cholera toxin, which is responsible for the voluminous stools of cholera, causes constitutive activation of adenylyl cyclase, resulting in the export of ions into the intestinal lumen. Environmental studies have demonstrated a close association between V. cholerae and many species of arthropods including insects. Here we report the susceptibility of the fruit fly, Drosophila melanogaster, to oral V. cholerae infection through a process that exhibits many of the hallmarks of human disease: (i) death of the fly is dependent on the presence of cholera toxin and is preceded by rapid weight loss; (ii) flies harboring mutant alleles of either adenylyl cyclase, Gsα, or the Gardos K+ channel homolog SK are resistant to V. cholerae infection; and (iii) ingestion of a K+ channel blocker along with V. cholerae protects wild-type flies against death. In mammals, ingestion of as little as 25 μg of cholera toxin results in massive diarrhea. In contrast, we found that ingestion of cholera toxin was not lethal to the fly. However, when cholera toxin was co-administered with a pathogenic strain of V. cholerae carrying a chromosomal deletion of the genes encoding cholera toxin, death of the fly ensued. These findings suggest that additional virulence factors are required for intoxication of the fly that may not be essential for intoxication of mammals. Furthermore, we demonstrate for the first time the mechanism of action of cholera toxin in a whole organism and the utility of D. melanogaster as an accurate, inexpensive model for elucidation of host susceptibility to cholera.

【 授权许可】

CC BY