Editors' ChoiceANTIBIOTIC RESISTANCE

Let’s start from the very beginning

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Science Translational Medicine  02 Aug 2017:
Vol. 9, Issue 401, eaao0977
DOI: 10.1126/scitranslmed.aao0977

Abstract

Methicillin-resistant Staphylococcus aureus likely evolved before the introduction of methicillin into clinical use.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major culprit for the rise in antimicrobial resistance (AMR) worldwide and is implicated in a wide range of infections. The mecA gene, required for methicillin resistance, is located on the staphylococcal cassette chromosome mec (SCCmec), a mobile genetic element. Exploiting the recent advances in genomic sequencing may advance our understanding of MRSA transmission dynamics, assisting in prevention of AMR spread.

Penicillin was introduced in the 1940s, quickly followed by the emergence of penicillin-resistant Staphylococcus aureus. Methicillin was introduced in 1959 to combat this penicillin resistance. MRSA was first isolated in 1960 in England, and two years later, MRSA had spread across Europe. Thus, it has long been thought that MRSA developed as a consequence of methicillin use.

Harkins et al. reconstructed the early evolution of MRSA using whole genome sequencing (WGS) of 209 of the earliest isolates of MRSA from England and Denmark (1960 to 1989). Traditional multilocus sequence typing had shown two major groups amongst these samples. However, WGS phylogeny reconstruction revealed a diverse population structure. Isolates from the early 1960s were spread across clades, suggesting that they did not evolve from a recently emerged clone. The authors focused on 122 isolates with precisely recorded dates and places of origin for temporal calibration of mecA acquisition and evolution. Bayesian phylogenetic analysis of SCCmec variation across isolates revealed that all variation could be mapped to nodes originating from a core phylogeny, suggesting that SCCmec was likely acquired in one isolated event. The researchers further showed in this analysis that the most recent common ancestor of these isolates was from 1946 or before, well before the introduction of methicillin.

Although the β lactamase enzyme is most commonly associated with penicillin resistance, mecA encodes an alternative resistance pathway. The authors concluded that widespread use of penicillin caused the evolution of MRSA and assert that methicillin provided the selective pressure for its spread. Their findings highlight the importance of careful surveillance for AMR, particularly with the introduction of new antimicrobials or shifts in prescribing practices that can cause selective pressure shifts toward unrecognized adaptations.

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