Christmas, B.A.F., Rolfe, M.D., Rose, M. et al. (1 more author) (2019) Staphylococcus aureus adaptation to aerobic low-redox-potential environments: implications for an intracellular lifestyle. Microbiology, 165 (7). pp. 779-791. ISSN 1465-2080
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. This is an author-produced version of a paper subsequently published in Microbiology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | redox sensing; aminoglycoside antiobiotics; intracellular pathogen; gene regulation; MRSA; small-colony variants |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 May 2019 11:23 |
Last Modified: | 03 Dec 2021 12:21 |
Status: | Published |
Publisher: | Microbiology Society |
Refereed: | Yes |
Identification Number: | 10.1099/mic.0.000809 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:146733 |