Synergistic Inhibition of MRSA by Chenodeoxycholic Acid and Carbapenem Antibiotics

Methicillin-resistant Staphylococcus aureus (MRSA) has posed a severe global health threat. In this study, we screened an antibiotic and non-antibiotic combination that provides a viable strategy to solve this issue by broadening the antimicrobial spectrum. We found that chenodeoxycholic acid (CDCA) could synergistically act with carbapenem antibiotics to eradicate MRSA-related infections. This synergy specifically targets MRSA and was also validated using 25 clinical MRSA strains using time-kill analysis. We speculated that the underlying mechanism was associated with the interaction of penicillin-binding proteins (PBPs). As a result, the synergistic efficiency of CDCA with carbapenems targeting PBP1 was better than that of beta-lactams targeting PBPs. Moreover, we showed that CDCA did not affect the expression level of PBPs, but sensitized MRSA to carbapenems by disrupting the cell membrane. In our study, we have revealed a novel synergistic combination of antibiotics and non-antibiotics to combat potential bacterial infections.

Automated summary

In this study, a viable strategy to solve the problem of methicillin-resistant Staphylococcus aureus (MRSA) was identified by screening an antibiotic and non-antibiotic combination that broadens the antimicrobial spectrum. Chenodeoxycholic acid (CDCA) was found to synergistically act with carbapenem antibiotics to eradicate MRSA-related infections. The underlying mechanism was associated with the interaction of penicillin-binding proteins (PBPs), and CDCA sensitized MRSA to carbapenems by disrupting the cell membrane.