Microbiology Editor's Choice: How does MRSA adapt to survive within a cell?

Posted on July 1, 2019   by Microbiology Society

Each month, a manuscript published in our flagship journal Microbiology is chosen by a member of the Editorial Board. This month, the paper is titled 'Staphylococcus aureus adaptation to aerobic low-redox-potential environments: implications for an intracellular lifestyle,' and was chosen by Professor Gail Preston.

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Professor Gail Preston: Methicillin-resistant Staphylococcus aureus (MRSA) is an antibiotic resistant 'superbug' that is associated with infections of blood, skin and soft tissues, and is a predominant cause of infections associated with medical implants.

Chronic MRSA infections are often characterised by the presence of slow-growing, antibiotic-resistant small-colony variants (SCVs) that are associated with the survival of bacteria within host cells. The redox potential of the host cell cytoplasm is low, and SCVs are often characterised by mutations resulting in impaired respiration, suggesting a link between intracellular growth and SCV formation.

In this study, Christmas and collaborators examine the effect of low redox environments on S. aureus physiology and gene expression and observe that exposure of bacteria to the host cytoplasmic reductant glutathione results in an increase in both antibiotic resistance and in the number of SCVs, along with a shift towards fermentative metabolism. This suggests that the low redox environment encountered by MRSA on invasion of host cells contributes to the formation of SCVs and the establishment of chronic, difficult to treat infections.

Staphylococcus aureus adaptation to aerobic low-redox-potential environments: implications for an intracellular lifestyle

Persistent staphylococcal infections are associated with the presence of slow-growing, antibiotic-tolerant bacteria residing within host cells. The host cytosol is aerobic but has a low redox potential, which is set by the presence of the reductant, glutathione. Experiments that mimicked these conditions in the laboratory showed that Staphylococcus aureus adapted by altering its gene expression to enhance fermentative metabolism. These changes, driven by redox-responsive gene regulators, resulted in phenotypes typical of ‘persister’ cells. Hence, it is suggested that adaptation to the low redox potential of the host cytosol could be important in establishing and maintaining persistent S. aureus infections.

We spoke with the corresponding author, Professor Jeff Green, about his research: 

What is your institution and how long have you been there?

University of Sheffield, 30 years.

What is your research area?

Microbial physiology, with particular interest in gene regulation and bacterial stress responses.

What inspired you to research this topic?

During my undergraduate biochemistry degree at the University of Hull I was fortunate to carry out my third-year project in Peter Large's laboratory to investigate aspects of the physiology of methazotrophic yeasts and became fascinated by the adaptability of microbes. 

What is the most rewarding part of your research?

Working with inspiring and creative people to reveal just a little more about how microbes 'work'.

What would you be doing if you weren't a scientist?

I cannot really imagine doing something else now but, if I had not been lucky enough to have been taught chemistry at secondary school by the inspirational Dr Haynes, I would probably have tried to secure an apprenticeship as a car mechanic.

To access the full paper, click here. Editor's Choice articles published in Microbiology are free to read.