Adaptive Metabolism of Staphylococcus aureus Revealed by Untargeted Metabolomics

Staphylococcus aureus (SA) is an opportunistic pathogen that can cause a wide spectrum of infections, from superficial skin inflammation to severe and potentially fatal and invasive diseases. Due to the many potential routes of infection, host-derived environmental signals (oxygen availability, nutrients, etc.) are vital for host colonization and thus contribute to SA's pathogenesis. To uncover the direct effects of environmental factors on SA metabolism, we performed a series of experiments in diverse culture environments and correlated our findings of SA's metabolic adaptation to some of the pathogen's known virulence factors. Untargeted metabolomics was conducted on a Thermo Q-Exactive high-resolution mass spectrometer. We detected 260 intracellular polar metabolites from our bacteria cultured under both aerobic and anaerobic conditions and in glucose- and dextrin-supplemented cultures. These metabolites were mapped to relevant metabolic pathways to elucidate the adaptive metabolic processes of both methicillin-sensitive SA (MSSA) and methicillin-resistant SA (MRSA). We also detected an increased expression of virulence genes agr-I and sea of MRSA supplemented with both glucose and dextrin by qPCR. With the metabolic data collected that may be associated with the adaptive growth and virulence of SA, our study could set up the foundations for future work to identify metabolic inhibitors/modulators to mitigate SA infections in different growth environments.