Presented by: Jarrod Smith
View Abstract
Intestinal mucus is thought to promote host health by functioning as a passive barrier that
distances potentially inflammatory symbiotic microbiota from the gut epithelium. Here we report
new evidence that beneficial microbes sense and respond to intestinal mucus by self-limiting
their intestinal distribution and inflammatory capacity, thus actively promoting host health. Our
work couples experimental microbial evolution with live imaging of bacterial dynamics and
transgenic reporters of host inflammation across the entire intestine to probe the distribution,
physiology, and inflammatory potential of a beneficial bacterium Aeromonas (Aer01) in its
native host, the larval zebrafish. Aer01 typically forms large aggregates in a distinct intestinal
region. Phenotypic and subsequent genomic analysis of evolved Aer01 that do not respond to
mucin in culture identified a putative mucin-sensing two-component system and surface associated mucin-binding adhesin that are crucial for driving Aer01 aggregation and localization in the host intestinal environment. Disruptions in either pathway dramatically transformed Aer01 intestinal distribution and aggregative clustering, stimulating the host innate immune system and leading to increased intestinal inflammation. We also found Aer01 mucin-sensing disruptions altered the community composition in defined 2- and 5- member communities. Together, our work highlights the important but largely unexplored role of microbial mucin sensory pathways in promoting host health and contributing to community composition.