RT Journal Article SR Electronic(1) A1 Christmas, Benjamin A. F. A1 Rolfe, Matthew D. A1 Rose, Matthew A1 Green, JeffreyYR 2019 T1 Staphylococcus aureus adaptation to aerobic low-redox-potential environments: implications for an intracellular lifestyle JF Microbiology, VO 165 IS 7 SP 779 OP 791 DO https://doi.org/10.1099/mic.0.000809 PB Microbiology Society, SN 1465-2080, AB Methicillin-resistant Staphylococcus aureus is a ‘superbug’ that is responsible for extensive death and morbidity. Chronic S. aureus infections are associated with the presence of intracellular bacteria and the host cytosol is an aerobic low-redox-potential (Eh) environment. How S. aureus adapts to aerobic low-Eh environments is understudied. A low external Eh, imposed by the non-metabolizable reductant dithiothreitol, resulted in transcriptional reprogramming mediated by the redox-responsive transcription factors AgrA, Rex and SrrBA, resulting in a shift towards fermentative metabolism. Accordingly, in the presence of the host cytoplasmic reductant glutathione, the aerobic respiration of S. aureus was impaired, the intracellular NADH:NAD+ ratio increased, lactate dehydrogenase was induced, resistance to the aminoglycoside antibiotic gentamicin was enhanced and greater numbers of small-colony variants (SCVs) were detected. These observations suggest that entry of S. aureus into the aerobic low-Eh environment of the host cytosol could result in adaptive responses that promote the formation of SCVs., UL https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000809