Skip to content

Research at St Andrews

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

Research output: Research - peer-reviewArticle

DOI

Open Access permissions

Open

Author(s)

Catriona P. Harkins, Bruno Pichon, Michel Doumith, Julian Parkhill, Henrik Westh, Alexander Tomasz, Herminia de Lencastre, Stephen D. Bentley, Angela M. Kearns, Matthew T. G. Holden

School/Research organisations

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.

Close

Details

Original languageEnglish
Article number130
Number of pages11
JournalGenome Biology
Volume18
DOIs
StatePublished - 20 Jul 2017

    Research areas

  • Staphylococcus aureas, MRSA, Antibiotic resistance

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Distinct evolutionary patterns of Neisseria meningitidis serogroup B disease outbreaks at two universities in the USA

    Hao, L., Holden, M. T. G., Wang, X., Andrew, L., Wellnitz, S., Hu, F., Whaley, M., Sammons, S., Knipe, K., Frace, M., McNamara, L. A., Liberator, P. & Anderson, A. S. 4 Apr 2018 In : Microbial Genomics. 10 p., 4

    Research output: Research - peer-reviewArticle

  2. Proposal of serovars 17 and 18 of Actinobacillus pleuropneumoniae based on serological and genotypic analysis

    Bossé, J. T., Li, Y., Sárközi, R., Fodor, L., Lacouture, S., Gottschalk, M., Amoribieta, M. C., Angen, Ø., Nedbalcova, K., Holden, M. T. G., Maskell, D. J., Tucker, A. W., Wren, B. W., Rycroft, A. N., Langford, P. R. & on behalf of the BRaDP1T consortium Apr 2018 In : Veterinary Microbiology. 217, p. 1-6

    Research output: Research - peer-reviewArticle

  3. Pseudomonas aeruginosa intensive care unit outbreak: winnowing of transmissions with molecular and genomic typing

    Parcell, B. J., Oravcova, K., Pinheiro, M., Holden, M. T. G., Phillips, G., Turton, J. F. & Gillespie, S. H. Mar 2018 In : Journal of Hospital Infection. 98, 3, p. 282-288 7 p.

    Research output: Research - peer-reviewArticle

  4. The microevolution and epidemiology of Staphylococcus aureus colonization during atopic eczema disease flare

    Harkins, C. P., Pettigrew, K. A., Oravcová, K., Gardner, J., Hearn, R. M. R., Rice, D., Mather, A. E., Parkhill, J., Brown, S. J., Proby, C. M. & Holden, M. T. G. Feb 2018 In : Journal of Investigative Dermatology. 138, 2, p. 336-343

    Research output: Research - peer-reviewArticle

  5. Genomic investigation unmasks evidence of transmission across mycobacterium abscessus cystic fibrosis patients

    Alateah, S., Peters, C., Dhasmana, D. J., Pettigrew, K., Fallon, R., Seagar, A., Sloan, D. J., Laurenson, I. F., Holden, M. & Gillespie, S. 15 Dec 2017 In : Thorax. 72, Suppl 3, p. A56-A56

    Research output: Research - peer-reviewAbstract

Related by journal

  1. The genome of the yellow potato cyst nematode, Globodera rostochiensis, reveals insights into the basis of parasitism and virulence

    Eves-van den Akker, S. , Laetsch, D. R. , Thorpe, P. , Lilley, C. J. , Danchin, E. G. J. , Da Rocha, M. , Rancurel, C. , Holroyd, N. E. , Cotton, J. A. , Szitenberg, A. , Grenier, E. , Montarry, J. , Mimee, B. , Duceppe, M-O. , Boyes, I. , Marvin, J. M. C. , Jones, L. M. , Yusup, H. B. , Lafond-Lapalme, J. , Esquibet, M. & 14 others Sabeh, M., Rott, M., Overmars, H., Finkers-Tomczak, A., Smant, G., Koutsovoulos, G., Blok, V., Mantelin, S., Cock, P. J. A., Phillips, W., Henrissat, B., Urwin, P. E., Blaxter, M. & Jones, J. T. 10 Jun 2016 In : Genome Biology. 17, 1, p. 1-23 23 p., 124

    Research output: Research - peer-reviewArticle

  2. Evolutionary dynamics of methicillin-resistant Staphylococcus aureus within a healthcare system

    Hsu, L-Y., Harris, S. R., Chlebowicz, M. A., Lindsay, J. A., Koh, T-H., Krishnan, P., Tan, T-Y., Hon, P-Y., Grubb, W. B., Bentley, S. D., Parkhill, J., Peacock, S. J. & Holden, M. T. 23 Apr 2015 In : Genome Biology. 16, 13 p., 81

    Research output: Research - peer-reviewArticle

  3. 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer

    Uribe-Lewis, S., Stark, R., Carroll, T., Dunning, M. J., Bachman, M., Ito, Y., Stojic, L., Halim, S., Vowler, S. L., Lynch, A. G., Delatte, B., de Bony, E. J., Colin, L., Defrance, M., Krueger, F., Silva, A. L., ten Hoopen, R., Ibrahim, A. E. K., Fuks, F. & Murrell, A. 1 Apr 2015 In : Genome Biology. 16, 15 p., 69

    Research output: Research - peer-reviewArticle

  4. The genome and life-stage specific transcriptomes of Globodera pallida elucidate key aspects of plant parasitism by a cyst nematode

    Cotton, J. A. , Lilley, C. J. , Jones, L. M. , Kikuchi, T. , Reid, A. J. , Thorpe, P. , Tsai, I. J. , Beasley, H. , Blok, V. , Cock, P. J. A. , Eves-van den Akker, S. , Holroyd, N. , Hunt, M. , Mantelin, S. , Naghra, H. , Pain, A. , Palomares-Rius, J. E. , Zarowiecki, M. , Berriman, M. , Jones, J. T. & 1 others Urwin, P. E. 3 Mar 2014 In : Genome Biology. 15, 3, 17 p., R43

    Research output: Research - peer-reviewArticle

ID: 250558359