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

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Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. / Harkins, Catriona P.; Pichon, Bruno; Doumith, Michel; Parkhill, Julian; Westh, Henrik; Tomasz, Alexander; de Lencastre, Herminia; Bentley, Stephen D.; Kearns, Angela M.; Holden, Matthew T. G.

In: Genome Biology, Vol. 18, 130, 20.07.2017.

Research output: Contribution to journalArticlepeer-review

Harvard

Harkins, CP, Pichon, B, Doumith, M, Parkhill, J, Westh, H, Tomasz, A, de Lencastre, H, Bentley, SD, Kearns, AM & Holden, MTG 2017, 'Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice', Genome Biology, vol. 18, 130. https://doi.org/10.1186/s13059-017-1252-9

APA

Harkins, C. P., Pichon, B., Doumith, M., Parkhill, J., Westh, H., Tomasz, A., de Lencastre, H., Bentley, S. D., Kearns, A. M., & Holden, M. T. G. (2017). Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biology, 18, [130]. https://doi.org/10.1186/s13059-017-1252-9

Vancouver

Harkins CP, Pichon B, Doumith M, Parkhill J, Westh H, Tomasz A et al. Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biology. 2017 Jul 20;18. 130. https://doi.org/10.1186/s13059-017-1252-9

Author

Harkins, Catriona P. ; Pichon, Bruno ; Doumith, Michel ; Parkhill, Julian ; Westh, Henrik ; Tomasz, Alexander ; de Lencastre, Herminia ; Bentley, Stephen D. ; Kearns, Angela M. ; Holden, Matthew T. G. / Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. In: Genome Biology. 2017 ; Vol. 18.

Bibtex - Download

@article{bb85ca343bf94b92b9e14f4eac5c20e2,
title = "Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice",
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 = "Staphylococcus aureas, MRSA, Antibiotic resistance",
author = "Harkins, {Catriona P.} and Bruno Pichon and Michel Doumith and Julian Parkhill and Henrik Westh and Alexander Tomasz and {de Lencastre}, Herminia and Bentley, {Stephen D.} and Kearns, {Angela M.} and Holden, {Matthew T. G.}",
note = "SDB, JP and MTGH were supported by Wellcome Trust grant 098051. CPH was supported by Wellcome Trust grant number 104241/z/14/z. Bioinformatics and computational biology analyses were supported by the University of St Andrews Bioinformatics Unit, which is funded by a Wellcome Trust ISSF award (grant 097831/Z/11/Z). AK, MD and BP received funding from Public Health England.",
year = "2017",
month = jul,
day = "20",
doi = "10.1186/s13059-017-1252-9",
language = "English",
volume = "18",
journal = "Genome Biology",
issn = "1465-6906",
publisher = "BioMed Central",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice

AU - Harkins, Catriona P.

AU - Pichon, Bruno

AU - Doumith, Michel

AU - Parkhill, Julian

AU - Westh, Henrik

AU - Tomasz, Alexander

AU - de Lencastre, Herminia

AU - Bentley, Stephen D.

AU - Kearns, Angela M.

AU - Holden, Matthew T. G.

N1 - SDB, JP and MTGH were supported by Wellcome Trust grant 098051. CPH was supported by Wellcome Trust grant number 104241/z/14/z. Bioinformatics and computational biology analyses were supported by the University of St Andrews Bioinformatics Unit, which is funded by a Wellcome Trust ISSF award (grant 097831/Z/11/Z). AK, MD and BP received funding from Public Health England.

PY - 2017/7/20

Y1 - 2017/7/20

N2 - 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.

AB - 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.

KW - Staphylococcus aureas

KW - MRSA

KW - Antibiotic resistance

U2 - 10.1186/s13059-017-1252-9

DO - 10.1186/s13059-017-1252-9

M3 - Article

C2 - 28724393

VL - 18

JO - Genome Biology

JF - Genome Biology

SN - 1465-6906

M1 - 130

ER -

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