Bacterial Peptidoglycan as a Food Digestive Signal that Facilitates Adaptation of Animals in Nature

Abstract

Food availability and usage is a major adaptive force for the successful survival of animals in nature. However, very little is known about the signal from food to activate the hosts digestive system, which facilitates animals to digest more diverse food in nature. Here, by using a food digestion system in C. elegans, we discover that bacterial peptidoglycan (PGN) is a unique food signal that activates animals to digest inedible food. We identified that a glycosylated protein BCF-1 in the gut that interacts directly with bacterial peptidoglycan. This interaction inhibits mitochondrial UPR (UPRmt) by regulating the release of a neuropeptide (NLP-3). Moreover, constitutive activation of UPRmt is sufficient to inhibit food digestion, which depends on innate immune PMK-1. Addition, inhibition of innate immune PMK-1 can counter the digest defects of bcf-1 mutants. Finally, we demonstrate that natural adaptation is reduced in animals with digestion defects. Thus, our study reveals that bacterial PGN-glycosylated protein interaction is essential for digestion though cell-non-autonomous UPRmt inhibition, which facilitates adaptation of the host animals by increasing ability to consume a wide range of foods in their natural environment.