Superbug MRSA susceptible to existing antibiotics

Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious problem, forcing doctors to turn to antibiotics other than penicillin or penicillin derivatives, or to different drug cocktails, which are often less effective in treating hospital and community based infections.

petri dishes

But new MRC funded research from scientists at the University of Cambridge and the Wellcome Sanger Institute has found that some MRSA infections could be tackled - and by using existing antibiotics.

The researchers found that MRSA isolates become susceptible to penicillin in combination with clavulanic acid: a widely-used beta-lactamase inhibitor for the treatment of kidney infections during pregnancy.

Using genome sequencing technology, the researchers were then able to identify which genes make MRSA susceptible to this combination of drugs by identifying several mutations centred around a protein known as a penicillin-binding protein 2a or PBP2a; a protein which enables MRSA strains to keep growing despite the presence of penicillin and other antibiotics derived from penicillin.

The team found that two of these mutations reduced the amount of PBP2a produced, while two other mutations increased the ability of penicillin to bind to PBP2a in the presence of clavulanic acid.

The team then looked at whole genome sequences of a diverse collection of MRSA strains and found that a significant number of them – including the dominant US300 clone in the United States – contained both mutations, suggesting that they too would be sensitive to the combination of drugs.

MRSA infections in two model systems, moths and mice, have since been successfully treated using a combination of the two drugs with the team now looking to expand into human trials.

Dr Jessica Boname, Head of Antimicrobial Resistance at the MRC, said: “This study demonstrates how a mechanistic understanding of resistance and access to clinical data can be used to find new ways to contain and control infections with existing resources.”

Dr Mark Holmes from the Department of Veterinary Medicine at the University of Cambridge said: “MRSA and other antibiotic-resistant infections are a major threat to modern medicine and we urgently need to find new ways to tackle them. Developing new medicines is extremely important, but can be a lengthy and expensive process. Our works suggests that already widely-available medicines could be used to treat one of the world’s major strains of MRSA.”

Dr Ewan Harrison, from the Wellcome Sanger Institute and the University of Cambridge, said: “This study highlights the importance of genomic surveillance – collecting and sequencing representative collections of bacterial strains. By combining the DNA sequencing data generated by genomic surveillance with laboratory testing of the strains against a broad selection of antibiotics, we may find other unexpected chinks in the armour of antibiotic-resistant bacteria that might give us new treatment options.”

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