Newswise — The replication of a bacterial virus is not necessary to cause lethal disease in a mouse model of a food-borne pathogen called Enterohemorrhagic Escherichia coli (EHEC), according to a study published January 10 in the open-access journal PLOS Pathogens by Sowmya Balasubramanian, John Leong and Marcia Osburne of Tufts University School of Medicine, and colleagues. The surprising findings could lead to the development of novel strategies for the treatment of EHEC and life-threatening kidney-related complications in children.
EHEC is a Shiga toxin-producing pathogen associated with serious disease outbreaks worldwide, including more than 390 food-poisoning outbreaks in the U.S. in the last two decades. Humans acquire EHEC by ingesting contaminated food or water, or through contact with animals or their environment. Infection may progress to life-threatening hemolytic uremic syndrome (HUS), the leading cause of kidney failure in children. Treatment for EHEC or HUS remains elusive, as antibiotics have been shown to exacerbate disease. The bacteria begin to produce Shiga toxin when a virus present in the EHEC genome is induced to leave its dormant state and begin to replicate, a process promoted by many antibiotics. Until now, it was generally believed that extensive virus replication was necessary for the bacteria to produce sufficient toxin to cause disease.
Using an EHEC disease mouse model, the authors show that an inducing signal needed to begin viral replication is essential for lethal disease. But surprisingly, sufficient Shiga toxin was produced to cause lethal mouse disease, even without viral replication. According to John Leong, one of the authors, “An important next step will be to learn what parts of the viral life cycle occur in human patients, and whether there are ways to prevent those aspects that lead to disease”.
Funding: This work was supported by National Institute of Health (https://www.nih.gov/) grants R21AI107587 and 2R01AI046454 to JML. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Citation: Balasubramanian S, Osburne MS, BrinJones H, Tai AK, Leong JM (2019) Prophage induction, but not production of phage particles, is required for lethal disease in a microbiome-replete murine model of enterohemorrhagic E. coli
Department of Immunology at Tufts University School of Medicine, Boston, MA, United States of America
Department of Molecular Biology and Microbiology at Tufts University School of Medicine, Boston, MA, United States of America
About PLOS Pathogens
PLOS Pathogens is the first Open Access journal for breakthroughs in understanding pathogens and their interactions with host organisms. The journal publishes original research and commentary that yield novel insights into pathogenesis that are of broad interest and importance to researchers studying pathogens and pathogen-host interactions. For more information, visit http://journals.plos.
Media and Copyright Information
For information about PLOS Pathogens relevant to journalists, bloggers and press officers, including details of our press release process and embargo policy, visit http://journals.plos.
PLOS journals publish under a Creative Commons Attribution License, which permits free reuse of all materials published with the article, so long as the work is cited.
About the Public Library of Science
Public Library of Science (PLOS) is a nonprofit Open Access (OA) publisher, innovator and advocacy organization dedicated to accelerating progress in science and medicine by leading a transformation in research communication. The PLOS suite of journals contain rigorously peer-reviewed Open Access research articles from all areas of science and medicine, together with expert commentary and analysis. In addition to journals, the organization advances innovations in scientific publishing through Collections, Communities and The PLOS Blog Network. Founded to catalyze a revolution in scientific publishing by demonstrating the value and feasibility of Open Access publication, PLOS is committed to innovative and forward-looking solutions to scientific communication. For more information, visit https://www.plos.org/