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Oxacillin alters the toxin expression profile of community-associated methicillin-resistant Staphylococcus aureus
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Rudkin, Justine K., Laabei, Maisem, Edwards, Andrew M., Joo, Hwang-Soo, Otto, Michael, Lennon, Katrina L., O'Gara, James P., Waterfield, Nicholas R. and Massey, Ruth C. (2014) Oxacillin alters the toxin expression profile of community-associated methicillin-resistant Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 58 (2). pp. 1100-1107. doi:10.1128/AAC.01618-13 ISSN 0066-4804.
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Official URL: https://doi.org/10.1128/AAC.01618-13
Abstract
The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a growing cause for concern. These strains are more virulent than health care-associated MRSA (HA-MRSA) due to higher levels of toxin expression. In a previous study, we showed that the high-level expression of PBP2a, the alternative penicillin binding protein encoded by the mecA gene on type II staphylococcal cassette chromosome mec (SCCmec) elements, reduced toxicity by interfering with the Agr quorum sensing system. This was not seen in strains carrying the CA-MRSA-associated type IV SCCmec element. These strains express significantly lower levels of PBP2a than the other MRSA type, which may explain their relatively high toxicity. We hypothesized that as oxacillin is known to increase mecA expression levels, it may be possible to attenuate the toxicity of CA-MRSA by using this antibiotic. Subinhibitory oxacillin concentrations induced PBP2a expression, repressed Agr activity, and, as a consequence, decreased phenol-soluble modulin (PSM) secretion by CA-MRSA strains. However, consistent with other studies, oxacillin also increased the expression levels of alpha-toxin and Panton-Valentine leucocidin (PVL). The net effect of these changes on the ability to lyse diverse cell types was tested, and we found that where the PSMs and alpha-toxin are important, oxacillin reduced overall lytic activity, but where PVL is important, it increased lytic activity, demonstrating the pleiotropic effect of oxacillin on toxin expression by CA-MRSA.
Item Type: | Journal Article | ||||||
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Subjects: | Q Science > QR Microbiology | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Antimicrobial Agents and Chemotherapy | ||||||
Publisher: | American Society for Microbiology | ||||||
ISSN: | 0066-4804 | ||||||
Official Date: | 1 February 2014 | ||||||
Dates: |
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Volume: | 58 | ||||||
Number: | 2 | ||||||
Page Range: | pp. 1100-1107 | ||||||
DOI: | 10.1128/AAC.01618-13 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) |
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