The introduction of methicillin into clinical practice is not what caused the emergence of methicillin resistant Staphylococcus aureus (MRSA), report researchers.
According to a collaborative study by the University of St Andrews, University of Dundee and the Wellcome Trust Sanger Institute, MRSA existed long before clinicians started using the antibiotic. The study authors say it was the previous widespread use of first-generation antibiotics that drove the emergence of MRSA.
3D render of methicillin resistant Staphylococcus aureus (MRSA) bacteria ©royaltystockphoto.com/ Shutterstock.com
MRSA was first observed in 1960, less than one year after the introduction of methicillin and epidemiological studies had implied that S. aureus became resistant to methicillin at some point around this period. However, Matthew Holden (University of St Andrews) and colleagues found that S.aureus acquired the methicillin resistance gene (mecA) fourteen years previously, back in the mid-1940s.
Holden emphasises the importance of the finding, warning that new drugs introduced to circumvent known resistance mechanisms can be rendered ineffective by unrecognized, pre-existing adaptations in the bacterial population.
For example, mecA produces a protein called PBP2a, which inhibits the binding of antibiotics to the bacterial cell wall and the use of penicillin in the 1940s led to the selection of S.aureus strains that carried the gene.
“These adaptations happen because - in response to exposure to earlier antibiotics - resistant bacterial strains are selected instead of non-resistant ones as bacteria evolve,” explains Holden.
As reported in Genome Biology, Holden and team performed whole genome sequencing of 209 original S.aureus isolates to reconstruct the evolutionary history of MRSA.
According to the results, MRSA emerged in the mid-1940s, following the acquisition of an ancestral type I SCCmec (staphylococcal cassette chromosome mec) element, a genetic sequence that includes the mecA gene.
"S. aureus has proven to be particularly adept at developing resistance in the face of new antibiotic challenges, rendering many antibiotics ineffective,” says Holden. “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."