Abstract
In a healthy gut, microbes are often aggregated with host mucus, yet the molecular basis for this organization and its impact on intestinal health are unclear. Mucus is a viscous physical barrier separating resident microbes from epithelia, but it also provides glycan cues that regulate microbial behaviors. Here, we describe a mucin-sensing pathway in an Aeromonas symbiont of zebrafish, Aer01. In response to the mucin-associated glycan N-acetylglucosamine, a sensor kinase regulates the expression of an aggregation-promoting adhesin we named MbpA. Upon MbpA disruption, Aer01 colonizes to normal levels but is largely planktonic and more pro-inflammatory. Increasing cell surface MbpA rescues these traits. MbpA-like adhesins are common in human-associated bacteria, and the expression of an Akkermansia muciniphila MbpA-like adhesin in MbpA-deficient Aer01 restores lumenal aggregation and reverses its pro-inflammatory character. Our work demonstrates how resident bacteria use mucin glycans to modulate behaviors congruent with host health.