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bioRxiv · 10.1101/2024.01.05.573998

Pathogen and host adapt pH responses during enteric infection

Woodward, S. E.·Neufeld, L. M. P.·Pena-Diaz, J.·Feng, W.·Serapio-Palacios, A.·Tarrant, I.·Finlay, B. B.
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Abstract

Enteric pathogens navigate distinct regional micro-environments within the intestine which cue important adaptive behaviours. We investigated the response of Citrobacter rodentium, a model of human pathogenic Escherichia coli infection, 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. rodentiums replicative niches further along the intestine, supported pathogen growth. Gastric pH, a key barrier to intestinal colonization, caused significant accumulation of intra-bacterial reactive oxygen species, 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 induced at colonic pH. However, we also found that host gastric pH decreases post-infection, 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 adaptive pH responses as an important component of host-pathogen co-evolution.

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Woodward, S. E., Neufeld, L. M. P., Pena-Diaz, J., Feng, W., Serapio-Palacios, A., Tarrant, I., Finlay, B. B.. 2024-01-05. Pathogen and host adapt pH responses during enteric infection. https://doi.org/10.1101/2024.01.05.573998

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