Prophage Induction Is Enhanced and Required for Renal Disease and Lethality in an EHEC Mouse Model

PLoS Pathogens

Jonathan H. Friedman¹  Karen Beeri²  David I. Friedman²  Jared L. Reynolds²  Katherine G. Skinner²  Jessica S. Tyler²  Christopher J. Alteri²  Kathryn A. Eaton² 

[1] Department of Mathwork, Mathworks, Natick, Massachusetts, United States of America;Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America

关键词: Bacteriophages;    Mouse models;    Gastrointestinal tract;    Enterohaemorrhagic Escherichia coli;    DNA damage;    Cats;    Toxins;    Lysis (medicine);   

DOI  :  10.1371/journal.ppat.1003236

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Enterohemorrhagic Escherichia coli (EHEC), particularly serotype O157:H7, causes hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies showed that Shiga toxin 2 (Stx2), the primary virulence factor expressed by EDL933 (an O157:H7 strain), is encoded by the 933W prophage. And the bacterial subpopulation in which the 933W prophage is induced is the producer of Stx2. Using the germ-free mouse, we show the essential role 933W induction plays in the virulence of EDL933 infection. An EDL933 derivative with a single mutation in its 933W prophage, resulting specifically in that phage being uninducible, colonizes the intestines, but fails to cause any of the pathological changes seen with the parent strain. Hence, induction of the 933W prophage is the primary event leading to disease from EDL933 infection. We constructed a derivative of EDL933, SIVET, with a biosensor that specifically measures induction of the 933W prophage. Using this biosensor to measure 933W induction in germ-free mice, we found an increase three logs greater than was expected from in vitro results. Since the induced population produces and releases Stx2, this result indicates that an activity in the intestine increases Stx2 production.

【 授权许可】

CC BY