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Genome Biol. 2017 Jul 20;18(1):130. doi: 10.1186/s13059-017-1252-9.

Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice.

Author information

1
School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK.
2
School of Medicine, University of Dundee, Dundee, DD1 9SY, UK.
3
Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, National Infection Service, Public Health England, Colindale, UK.
4
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
5
Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark.
6
Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
7
Laboratory of Microbiology and Infectious Diseases, The Rockefeller University, New York, USA.
8
Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa, Oeiras, Portugal.
9
School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK. mtgh@st-andrews.ac.uk.
10
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. mtgh@st-andrews.ac.uk.

Abstract

BACKGROUND:

The spread of drug-resistant bacterial pathogens poses a major threat to global health. It is widely recognised that the widespread use of antibiotics has generated selective pressures that have driven the emergence of resistant strains. Methicillin-resistant Staphylococcus aureus (MRSA) was first observed in 1960, less than one year after the introduction of this second generation beta-lactam antibiotic into clinical practice. Epidemiological evidence has always suggested that resistance arose around this period, when the mecA gene encoding methicillin resistance carried on an SCCmec element, was horizontally transferred to an intrinsically sensitive strain of S. aureus.

RESULTS:

Whole genome sequencing a collection of the first MRSA isolates allows us to reconstruct the evolutionary history of the archetypal MRSA. We apply Bayesian phylogenetic reconstruction to infer the time point at which this early MRSA lineage arose and when SCCmec was acquired. MRSA emerged in the mid-1940s, following the acquisition of an ancestral type I SCCmec element, some 14 years before the first therapeutic use of methicillin.

CONCLUSIONS:

Methicillin use was not the original driving factor in the evolution of MRSA as previously thought. Rather it was the widespread use of first generation beta-lactams such as penicillin in the years prior to the introduction of methicillin, which selected for S. aureus strains carrying the mecA determinant. Crucially this highlights how new drugs, introduced to circumvent known resistance mechanisms, can be rendered ineffective by unrecognised adaptations in the bacterial population due to the historic selective landscape created by the widespread use of other antibiotics.

KEYWORDS:

Antibiotic resistance; MRSA; Staphylococcus aureus

PMID:
28724393
PMCID:
PMC5517843
DOI:
10.1186/s13059-017-1252-9
[Indexed for MEDLINE]
Free PMC Article

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