Skip to content

Research at St Andrews

Old drugs to treat resistant bugs: methicillin-resistant Staphylococcus aureus isolates with mecC are susceptible to a combination of penicillin and clavulanic acid

Research output: Research - peer-reviewArticle

DOI

Open Access permissions

Open

Author(s)

Xiaoliang Ba, Ewan M. Harrison, Andrew L. Lovering, Nicholas Gleadall, Ruth Zadoks, Julian Parkhill, Sharon J. Peacock, Matthew T. G. Holden, Gavin K. Paterson, Mark A. Holmes

School/Research organisations

Abstract

β-Lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by mecA) with a low affinity for β-lactam antibiotics. Recently, a novel variant of mecA, known as mecC, was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that mecC-encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum β-lactam resistance in MRSA strains carrying mecC (mecC-MRSA strains) is mediated by a combination of both PBP2c and the distinct β-lactamase encoded by the blaZ gene of strain LGA251 (blaZLGA251), which is part of mecC-encoding staphylococcal cassette chromosome mec (SCCmec) type XI. We further demonstrate that mecC-MRSA strains are susceptible to the combination of penicillin and the β-lactam inhibitor clavulanic acid in vitro and that the same combination is effective in vivo for the treatment of experimental mecC-MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between mecA- and mecC-encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of mecC-MRSA infections.
Close

Details

Original languageEnglish
Pages (from-to)7396-7404
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number12
Early online date21 Sep 2015
DOIs
StatePublished - Dec 2015

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

View graph of relations

Related by author

  1. Comparative sequence analysis of the capsular polysaccharide loci of Actinobacillus pleuropneumoniae serovars 1-18, and development of two multiplex PCRs for comprehensive capsule typing

    Bossé, J. T., Li, Y., Fernandez Crespo, R., Lacouture, S., Gottschalk, M., Sárközi, R., Fodor, L., Casas Amoribieta, M., 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 20 May 2018 In : Veterinary Microbiology. 220, p. 83-89 7 p.

    Research output: Research - peer-reviewArticle

  2. An outbreak of Streptococcus pyogenes in a mental health facility: advantage of well-timed whole-genome sequencing over emm typing

    Bergin, S. M. , Periaswamy, B. , Barkham, T. , Chua, H. C. , Mok, Y. M. , Fung, D. S. S. , Su, A. H. C. , Lee, Y. L. , Chua, M. L. I. , Ng, P. Y. , Soon, W. J. W. , Chu, C. W. , Tan, S. L. , Meehan, M. , Ang, B. S. P. , Leo, Y. S. , Holden, M. T. G. , De, P. , Hsu, L. Y. , Chen, S. L. & 2 others de Sessions, P. F. & Marimuthu, K. 9 May 2018 In : Infection Control and Hospital Epidemiology. First View, 9 p.

    Research output: Research - peer-reviewArticle

  3. The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from Atopic Dermatitis patients

    Harkins, C. P., McAleer, M. A., Bennett, D., McHugh, M., Fleury, O. M., Pettigrew, K. A., Oravcová, K., Parkhill, J., Proby, C. M., Dawe, R. S., Geoghegan, J. A., Irvine, A. D. & Holden, M. T. G. 5 May 2018 (Accepted/In press) In : British Journal of Dermatology. In press

    Research output: Research - peer-reviewArticle

  4. 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. Apr 2018 In : Microbial Genomics. 4, 4, 10 p., e000155

    Research output: Research - peer-reviewArticle

  5. 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

Related by journal

  1. TonB-dependent receptor repertoire of pseudomonas aeruginosa for uptake of siderophore-drug conjugates

    Luscher, A., Moynie, L., Auguste, P. S., Bumann, D., Mazza, L., Pletzer, D., Naismith, J. H. & Köhlera, T. Jun 2018 In : Antimicrobial Agents and Chemotherapy. 62, 6, 11 p., e00097-18

    Research output: Research - peer-reviewArticle

  2. Pharmacokinetics, tolerability, and bacteriological response of rifampin administered at 600, 900, and 1,200 milligrams daily in patients with pulmonary tuberculosis

    Aarnoutse, R. E., Kibiki, G. S., Reither, K., Semvua, H. H., Haraka, F., Mtabho, C. M., Mpagama, S. G., van den Boogaard, J., Sumari-de Boer, I. M., Magis-Escurra, C., Wattenberg, M., Logger, J. G. M., te Brake, L. H. M., Hoelscher, M., Gillespie, S. H., Colbers, A., Phillips, P. P. J., Plemper van Balen, G., Boeree, M. J. & PanACEA Consortium 1 Nov 2017 In : Antimicrobial Agents and Chemotherapy. 61, 11, e01054-17

    Research output: Research - peer-reviewArticle

  3. Genetic determinants of the pharmacokinetic variability of rifampin in Malawian adults with pulmonary tuberculosis

    Sloan, D. J., McCallum, A. D., Schipani, A., Egan, D., Mwandumba, H. C., Ward, S. A., Waterhouse, D., Banda, G., Allain, T. J., Owen, A., Khoo, S. H. & Davies, G. R. 1 Jul 2017 In : Antimicrobial Agents and Chemotherapy. 61, 7, 9 p., e00210-17

    Research output: Research - peer-reviewArticle

ID: 221686621