St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

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

Thumbnail
View/Open
Ba_2015_OldDrugs_AAC_7396.pdf (3.620Mb)
Date
12/2015
Author
Ba, Xiaoliang
Harrison, Ewan M.
Lovering, Andrew L.
Gleadall, Nicholas
Zadoks, Ruth
Parkhill, Julian
Peacock, Sharon J.
Holden, Matthew T. G.
Paterson, Gavin K.
Holmes, Mark A.
Keywords
RA0421 Public health. Hygiene. Preventive Medicine
NDAS
Metadata
Show full item record
Altmetrics Handle Statistics
Altmetrics DOI Statistics
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.
Citation
Ba , X , Harrison , E M , Lovering , A L , Gleadall , N , Zadoks , R , Parkhill , J , Peacock , S J , Holden , M T G , Paterson , G K & Holmes , M A 2015 , ' Old drugs to treat resistant bugs : methicillin-resistant Staphylococcus aureus isolates with mecC are susceptible to a combination of penicillin and clavulanic acid ' , Antimicrobial Agents and Chemotherapy , vol. 59 , no. 12 , pp. 7396-7404 . https://doi.org/10.1128/AAC.01469-15
Publication
Antimicrobial Agents and Chemotherapy
Status
Peer reviewed
DOI
https://doi.org/10.1128/AAC.01469-15
ISSN
0066-4804
Type
Journal article
Rights
© 2016, American Society for Microbiology. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at aac.asm.org / https://dx.doi.org/10.1128/AAC.01469-15
Description
This work was supported by a Medical Research Council (MRC) partnership grant (G1001787/1) held between the Department of Veterinary Medicine, University of Cambridge (M.A.H.), the School of Clinical Medicine, University of Cambridge (S.J.P.), the Moredun Research Institute (R.Z.), and the Wellcome Trust Sanger Institute (J.P. and S.J.P.).
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/9241

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter