MprF-mediated immune evasion is necessary forLactiplantibacillus plantarumresilience inDrosophilagut during inflammation

Abstract

AbstractBackgroundMultiple peptide resistance factor (MprF) confers resistance to cationic antimicrobial peptides (AMPs) in several pathogens, thereby enabling evasion of the host immune response. While MprF has been proven to be crucial for the virulence of various pathogens, its role in commensal gut bacteria remains uncharacterized. To close this knowledge gap, we used a common gut commensal of animals,Lactiplantibacillus plantarum, and its natural host, the fruit flyDrosophila melanogaster, as an experimental model to investigate the role of MprF in commensal-host interactions.ResultsTheL. plantarumΔmprFmutant that we generated exhibited deficiency in the synthesis of lysyl-phosphatidylglycerol (Lys-PG), resulting in increased negative cell surface charge and increased susceptibility to AMPs. Susceptibility to AMPs had no effect on ΔmprFmutant’s ability to colonize guts of uninfected flies. However, we observed significantly reduced abundance of the ΔmprFmutant after infection-induced inflammation in the guts of wild-type flies but not flies lacking AMPs. These results demonstrate that host AMPs reduce the abundance of the ΔmprFmutant during infection. We found in addition that the ΔmprFmutant compared to wild-typeL. plantaruminduces a stronger intestinal immune response in flies due to the increased release of immunostimulatory peptidoglycan fragments, indicating an important role of MprF in promoting host tolerance to commensals.ConclusionOverall, our results demonstrate that MprF, besides its well-characterized role in pathogen immune evasion and virulence, is also an important resilience factor in maintaining stable microbiota-host interactions during intestinal inflammation.