Methicillin resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to a study published in the open access journal Genome Biology. It was the widespread use of earlier antibiotics such as penicillin rather than of methicillin itself which caused MRSA to emerge, researchers at the University of St Andrews, and the Wellcome Trust Sanger Institute, UK suggest.
The researchers found that S. aureus acquired the gene that confers methicillin resistance - mecA - as early as the mid-1940s - fourteen years before the first use of methicillin.
Professor Matthew Holden, molecular microbiologist at the University of St Andrews, the corresponding author said: "Our study provides important lessons for future efforts to combat antibiotic resistance. It shows that new drugs which are introduced to circumvent known resistance mechanisms, as methicillin was in 1959, can be rendered ineffective by unrecognized, pre-existing adaptations in the bacterial population. These adaptations happen because - in response to exposure to earlier antibiotics - resistant bacterial strains are selected instead of non-resistant ones as bacteria evolve."
The mecA gene confers resistance by producing a protein called PBP2a, which decreases the binding efficiency of antibiotics used against S. aureus to the bacterial cell wall. The introduction of penicillin in the 1940s led to the selection of S. aureus strains that carried the methicillin resistance gene.
Dr. Catriona Harkins, clinical lecturer in dermatology at the University of Dundee, the first author of the study said: "Within a year of methicillin being first introduced to circumvent penicillin resistance, strains of S. aureus were found that were already resistant to methicillin. In the years that followed resistance spread rapidly in and outside of the UK. Five decades on from the appearance of the first MRSA, multiple MRSA lineages have emerged which have acquired different variants of the resistance gene."
To uncover the origins of the very first MRSA and to trace its evolutionary history, the researchers sequenced the genomes of a unique collection of 209 historic S. aureus isolates. The oldest of these isolates were identified over 50 years ago by the S. aureus reference laboratory of Public Health England and have been stored ever since in their original freeze-dried state. The researchers also found genes in these isolates that confer resistance to numerous other antibiotics, as well as genes associated with decreased susceptibility to disinfectants.
Professor Holden said: "S. aureus has proven to be particularly adept at developing resistance in the face of new antibiotic challenges, rendering many antibiotics ineffective. This remains one of the many challenges in tackling the growing problem of antimicrobial resistance. In order to ensure that future antibiotics retain their effectiveness for as long as possible, it is essential that effective surveillance mechanisms are combined with the use of genome sequencing to scan for the emergence and spread of resistance."
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Notes to editors:
1. Research article:
Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice.
Harkins et al Genome Biology 2017
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2. Genome Biology publishes outstanding research in all areas of biology and biomedicine studied from a genomic and post-genomic perspective. The current impact factor is 11.908 and the journal is ranked 4th among research journals in the Genetics and Heredity category by Thomson Reuters. Genome Biology is the highest ranked open access journal in the category.
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4. Founded in the 15th century, St Andrews is Scotland's first university and the third oldest in the English speaking world. Teaching began in the community of St Andrews on the east coast of Scotland in 1410 and the University was formally constituted by the issue of Papal Bull in 1413.
The university is one of Europe's most research intensive seats of learning, over a quarter of its turnover comes from research grants and contracts. It is one of the top rated universities in Europe for research, teaching quality and student satisfaction and is consistently ranked among the UK's top five in leading independent league tables.
Its international reputation for delivering high quality teaching and research and student satisfaction make it one of the most sought after destinations for students from the UK, Europe and overseas. It is Scotland's most international university, forty five per cent of the student body of 8,400 is from overseas. The University enjoys a 1:12 academic staff to student ratio and is ranked top in the UK National Student Survey.
The University was the highest ranking Scottish University in The Times and Sunday Times University Guide 2017, and named UK University of the Year for Teaching Quality. The 2018 Guardian University Guide ranked the University as top in Scotland and the third best university in the UK. St Andrews also came 92nd in the QS University World Rankings 2017/18 - marking over a decade as one of the world's top 100 universities.
The University of St Andrews also ranks highly for our research, with a particularly high percentage of our research in Psychology and English Literature rated at 4* world-leading by the Research Excellence Framework (REF) 2014.
5. The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.