Both pathogen and host dynamically adapt pH responses along the intestinal tract during enteric bacterial infection

Enteric pathogens navigate distinct regional microenvironments within the intestine that cue important adaptive behaviors. We investigated the response of Citrobacter rodentium, a model of human pathogenic Escherichia coli infection in mice, to regional gastrointestinal pH. We found that small intes...

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Bibliographic Details
Published in:	PLoS biology Vol. 22; no. 8; p. e3002761
Main Authors:	Woodward, Sarah E, Neufeld, Laurel M P, Peña-Díaz, Jorge, Feng, Wenny, Serapio-Palacios, Antonio, Tarrant, Isabel, Deng, Wanyin, Finlay, B Brett
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 15-08-2024 Public Library of Science (PLoS)
Subjects:	Adaptation, Physiological Animals Bacteria, Pathogenic Bacterial infections Biology and Life Sciences Citrobacter rodentium - pathogenicity Citrobacter rodentium - physiology Development and progression Enterobacteriaceae Infections - metabolism Enterobacteriaceae Infections - microbiology Escherichia coli - metabolism Escherichia coli - physiology Female Health aspects Host-bacteria relationships Host-Pathogen Interactions Humans Hydrogen-Ion Concentration Intestines - microbiology Medicine and Health Sciences Mice Mice, Inbred C57BL Reactive Oxygen Species - metabolism Research and Analysis Methods Virulence Canada
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Summary:	Enteric pathogens navigate distinct regional microenvironments within the intestine that cue important adaptive behaviors. We investigated the response of Citrobacter rodentium, a model of human pathogenic Escherichia coli infection in mice, to regional gastrointestinal pH. We found that small intestinal pH (4.4-4.8) triggered virulence gene expression and altered cell morphology, supporting initial intestinal attachment, while higher pH, representative of C. rodentium's replicative niches further along the murine intestine, supported pathogen growth. Gastric pH, a key barrier to intestinal colonization, caused significant accumulation of intra-bacterial reactive oxygen species (ROS), inhibiting growth of C. rodentium and related human pathogens. Within-host adaptation increased gastric acid survival, which may be due to a robust acid tolerance response (ATR) induced at colonic pH. However, the intestinal environment changes throughout the course of infection. We found that murine gastric pH decreases postinfection, corresponding to increased serum gastrin levels and altered host expression of acid secretion-related genes. Similar responses following Salmonella infection may indicate a protective host response to limit further pathogen ingestion. Together, we highlight interlinked bacterial and host adaptive pH responses as an important component of host-pathogen coevolution.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1544-9173 1545-7885 1545-7885
DOI:	10.1371/journal.pbio.3002761