Nontargeted Metabolomics Analysis of Oxacillin Resistance in Staphylococcus Aureus

Abstract BackgroundStaphylococcus aureus has acquired resistance to antibiotics in the long-term struggle against antibiotics. Treatment of Staphylococcus aureus infection has become more difficult. In this study, based on nontargeted metabolic figure printing technique, the metabolome of a pair of isogenic methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA) strains treated with the sublethal dose of oxacillin was characterize to investigate the mechanism of antibiotic resistance.ResultsMassive alternations of metabolite expression were observed in both MSSA and MRSA treated with oxacillin. The results of accurate mass and mass fragmentation analysis showed that 7 and 29 metabolites of MRSA and MSSA have changed significantly after oxacillin treatment. The dysregulated metabolites suggested that CoA and fatty acids could help Staphylococcus aureus survive under antibiotic stress. Metabolic pathways engaged in antibiotic resistance were discovered through pathway enrichment analysis. The enriched pathways suggested that DNA repairing and flavin biosynthesis are universal pathways to help MSSA and MRSA survive under antibiotic stress. Compared with MSSA, MRSA systematically and effectively fight against oxacillin through precisely controlling energy producing, PBP2a substrate biosynthesis and antioxidant function. ConclusionsCoenzyme A and fatty acids help both MSSA and MRSA survive under the antibiotic stress. MSSA was susceptible to oxacillin and was forced to response. On the contrary, MRSA systematically and effectively fight against oxacillin. The different metabolome responses of MSSA and MRSA provide us with new insights into how Staphylococcus aureus develops antibiotics resistance.