Peptidoglycan recognition protein SC (PGRP‐SC) shapes gut microbiota richness, diversity and composition by modulating immunity in the house fly Musca domestica

The gastrointestinal tract of all animals, including insects, is colonized by a remarkable array of microorganisms which are referred to collectively as the gut microbiota. The hosts establish mutually beneficial interactions with the gut microbiota. However, the mechanisms shaping these interactions remain to be better understood. Here, we investigated the roles of Musca domestica peptidoglycan recognition protein SC (MdPGRP‐SC), a secreted pattern recognition receptor, in shaping the gut microbial community structure by using biochemical and high‐throughput sequencing approaches. The recombinant MdPGRP‐SC (rMdPGRP‐SC) could strongly bind various pathogen‐associated molecular patterns (PAMPs) including peptidoglycan, lipopolysaccharide and D‐galactose, and exhibited mild affinity to β‐1, 3‐glucan and D‐mannose. Meanwhile, rMdPGRP‐SC could also bind different kinds of microorganisms, including gram‐positive bacteria (Bacillus subtilis and Staphylococcus aureus), gram‐negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and yeast (Pichia pastoris). rMdPGRP‐SC also exhibited weak antibacterial activity against Bacillus subtilis. Knockdown of MdPGRP‐SC by RNAi reduced the persistence of ingested E. coli and a load of indigenous microbiota in the larval gut significantly. In addition, depleted MdPGRP‐SC also altered the gut microbiota composition and led to increased ratios of Gram‐negative bacteria. We hypothesize that MdPGRP‐SC is involved in maintaining gut homeostasis by modulating the immune intensity of the gut through multiple mechanisms, including degrading or neutralizing various PAMPs and selectively suppressing the growth of some bacteria. Considering the functional conservation of the peptidoglycan recognition protein (PGRP) family in insects, the catalytic PGRPs might be promising candidate targets not only for pest and vector control but also for the treatment of bacterial infection in insect farming. Musca domestica PGRP‐SC (MdPGRP‐SC) is a pattern recognition receptor with multiple pathogen‐associated molecular patterns recognition capabilities and microbial binding activities. MdPGRP‐SC negatively regulates intestinal antimicrobial peptide expression. Knockdown of MdPGRP‐SC alters the gut microbiota composition and richness.