Therapeutic potential of isoallolithocholic acid in methicillin-resistant Staphylococcus Aureus peritoneal infection.

Abstract

A significant increase in multidrug-resistant Methicillin-resistant Staphylococcus aureus (MRSA) infections has made it crucial to explore new antimicrobial drugs and strategies. Emerging evidence suggests that the bile acid metabolite isoallolithocholic acid (isoallo-LCA) may contribute to reducing the risk of infection among centenarians. However, its precise role remains somewhat ambiguous and necessitates further investigation. This study aims to investigate the roles of isoallo-LCA in MRSA-associated peritoneal infection. The effects of isoallo-LCA on peritoneal infection are examined in a MRSA-induced peritoneal infected model. Antibacterial activity, biofilm formation assay, and bacterial membrane permeability experiments are conducted to explore the mechanisms involved. Our findings demonstrate that isoallo-LCA effectively suppresses the replication of MRSA with minimal adverse effects on mammalian cells. Furthermore, isoallo-LCA significantly inhibits the formation of bacterial biofilms and eradicates existing bacterial biofilms of MRSA. Administration of isoallo-LCA reduces MRSA colonization in peritoneal organs and alleviates peritonitis-related inflammation and damage in a MRSA-infected peritonitis mice. Mechanistically, isoallo-LCA exhibits potent bactericidal activity against MRSA by disrupting the integrity and permeability of bacterial cells. In addition, isoallo-LCA also enhances the macrophage phagocytosis. In conclusion, our results suggest that isoallo-LCA could be an effective treatment for infections caused by MRSA.