LAUSR

Graphical abstract Figure. No Caption available. HighlightsA targeted mass spectrometry based metabolomics detecting more than 200 metabolites.Exogenous glucose enhanced the killing of methicillin treated S. aureus.Metabolic reprogramming was detected after glucose and methicillin co‐treatment.Massive S. aureus metabolic profile shift was discovered after co‐treatment.Both MSSA and MRSA responded to glucose and methicillin co‐treatment. Abstract Traditional strategies in developing novel drugs to treat antibiotic‐resistant S. aureus have not been very successful to date, therefore, there is an urgent need for creative usage of existing agents that can treat and control S. aureus infection. This study demonstrated that a combination of glucose and a sublethal dose of antibiotic can reduce the survivability of S. aureus in a glucose concentration‐dependent manner. Mass spectrometry‐based targeted metabolic profiling detected massive metabolic profile shift of both methicillin‐susceptible and resistant S. aureus after methicillin and glucose co‐treatment. The dramatic alteration of metabolites from these metabolic pathways can be detected when 10 mg/L or higher concentration of glucose were added to methicillin treated culture. Our data also indicated that multiple biochemical metabolic pathways, including pyrimidine metabolism and valine, leucine, and isoleucine degradation showed a significant difference (p < 0.01) in comparison of control groups to glucose treatment groups. Taken together, this pilot study suggested that exogenous glucose in combination with a sublethal dose of antibiotics can disturb the metabolism of both methicillin‐susceptible and resistant S. aureus, and enhance the antibiotic bactericidal effect.