vibrio cholerae infection of drosophila melanogaster mimics the human disease cholera霍乱弧菌感染黑腹果蝇模拟人类疾病霍乱.pdfVIP

Vibrio cholerae Infection of Drosophila melanogaster Mimics the Human Disease Cholera 1 2 3 3 3 4 Nathan S. Blow , Robert N. Salomon , Kerry Garrity , Isabelle Reveillaud , Alan Kopin , F. Rob Jackson , 1* Paula I. Watnick 1 Department of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Boston, Massachusetts, United States of America, 2 Department of Pathology, Tufts-New England Medical Center, Boston, Massachusetts, United States of America, 3 Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, Massachusetts, United States of America, 4 Department of Neurosciences, Tufts University School of Medicine, Boston, Massachusetts, United States of America 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, Gsa, or the Gardos Kþ channel homolog SK are resistant to V. cholerae infection; and (iii) ingestion of a Kþ channel blocker along with V. cholerae pr