Transmission of Vibrio cholerae Is Antagonized by Lytic Phage and Entry into the Aquatic Environment

PLoS Pathogens

Regina C. LaRocque¹  Stephen B. Calderwood¹  Andrew Camilli²  Eric J. Nelson²  Lori Bourassa²  Stefan Schild³  Firdausi Qadri⁴  Ashrafuzzaman Chowdhury⁵  James Flynn⁶  Yue Shao⁶ 

[1] Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America, and Harvard Medical School, Boston, Massachusetts, United States of America;Howard Hughes Medical Institute and the Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America;Institut fuer Molekulare Biowissenschaften, Karl-Franzens-Universitaet Graz, Graz, Austria;International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh;Microbiology Department, Jahangirnagar University, Savar, Dhaka, Bangladesh;Tufts Expression Array Core (TEAC) Facility, Tufts University School of Medicine, Boston, Massachusetts, United States of America

关键词: Bacteriophages;    Vibrio cholerae;    Ponds;    Microarrays;    Cholera;    Mouse models;    Aquatic environments;    Principal component analysis;   

DOI  :  10.1371/journal.ppat.1000187

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Cholera outbreaks are proposed to propagate in explosive cycles powered by hyperinfectious Vibrio cholerae and quenched by lytic vibriophage. However, studies to elucidate how these factors affect transmission are lacking because the field experiments are almost intractable. One reason for this is that V. cholerae loses the ability to culture upon transfer to pond water. This phenotype is called the active but non-culturable state (ABNC; an alternative term is viable but non-culturable) because these cells maintain the capacity for metabolic activity. ABNC bacteria may serve as the environmental reservoir for outbreaks but rigorous animal studies to test this hypothesis have not been conducted. In this project, we wanted to determine the relevance of ABNC cells to transmission as well as the impact lytic phage have on V. cholerae as the bacteria enter the ABNC state. Rice-water stool that naturally harbored lytic phage or in vitro derived V. cholerae were incubated in a pond microcosm, and the culturability, infectious dose, and transcriptome were assayed over 24 h. The data show that the major contributors to infection are culturable V. cholerae and not ABNC cells. Phage did not affect colonization immediately after shedding from the patients because the phage titer was too low. However, V. cholerae failed to colonize the small intestine after 24 h of incubation in pond water—the point when the phage and ABNC cell titers were highest. The transcriptional analysis traced the transformation into the non-infectious ABNC state and supports models for the adaptation to nutrient poor aquatic environments. Phage had an undetectable impact on this adaptation. Taken together, the rise of ABNC cells and lytic phage blocked transmission. Thus, there is a fitness advantage if V. cholerae can make a rapid transfer to the next host before these negative selective pressures compound in the aquatic environment.

【 授权许可】

CC BY