Pathogen and host adapt pH responses during enteric infection

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.