1887

Abstract

Methicillin-resistant is a ‘superbug’ that is responsible for extensive death and morbidity. Chronic infections are associated with the presence of intracellular bacteria and the host cytosol is an aerobic low-redox-potential (E) environment. How adapts to aerobic low-E environments is understudied. A low external E, 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 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 into the aerobic low-E environment of the host cytosol could result in adaptive responses that promote the formation of SCVs.

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2019-07-01
2024-03-28
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