Abstract Members of gut microbiota are confronted by the epithelial immune system suggesting that resistance is crucial for chronical gut colonization. We show that the insect Riptortus pedestris produces massively hundreds of specific antimicrobial peptides (AMPs), the Crypt-specific Cysteine-Rich peptides (CCRs), in the posterior midgut that houses a mono-specific bacterial community. CCRs have membrane-damaging antimicrobial activity against diverse bacteria but gut symbionts have elevated resistance. Tn-seq determined the genetic repertoire in the gut symbiont Caballeronia insecticola to manage AMP stress, identifying novel pathways targeted by AMPs in addition to cell envelope functions. Mutants in the corresponding genes have reduced capacity to colonize the gut, demonstrating that CCRs create a selective barrier and resistance is a key attribute of gut symbionts.

Hundreds of antimicrobial peptides create a selective barrier for insect gut symbionts