MprF-mediated immune evasion is necessary for Lactiplantibacillus plantarum resilience in the Drosophila gut during inflammation.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Drosophila melanogaster*/immunology ; Drosophila melanogaster*/microbiology ; Immune Evasion*/immunology ; Inflammation*/immunology; Animals ; Lactobacillus plantarum/immunology ; Bacterial Proteins/immunology ; Bacterial Proteins/metabolism ; Bacterial Proteins/genetics ; Antimicrobial Peptides/immunology ; Lactobacillaceae/immunology

Multiple peptide resistance factor (MprF) confers resistance to cationic antimicrobial peptides (AMPs) in several pathogens, thereby enabling evasion of the host immune response. The role of MprF in commensals remains, however, uncharacterized. To close this knowledge gap, we used a common gut commensal of animals, Lactiplantibacillus plantarum, and its natural host, the fruit fly Drosophila melanogaster, as an experimental model to investigate the role of MprF in commensal-host interactions. The L. plantarum ΔmprF mutant 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 ΔmprF mutant's ability to colonize guts of uninfected flies. However, we observed significantly reduced abundance of the ΔmprF mutant after infection-induced inflammation in the guts of wild-type flies but not of flies lacking AMPs. Additionally, we found that the ΔmprF mutant compared to wild-type L. plantarum induces 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. Our further analysis suggests that MprF-mediated lipoteichoic acid modifications are involved in host immunomodulation. Overall, our results demonstrate that MprF, besides its well-characterized role in pathogen immune evasion and virulence, is also an important commensal resilience factor.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Arias-Rojas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (Bacterial Proteins)
0 (Antimicrobial Peptides)

Date Created: 20240819 Date Completed: 20240829 Latest Revision: 20240912

20240912

PMC11361745

10.1371/journal.ppat.1012462

39159259