Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections



Waters, EM, Rudkin, JK, Coughlan, S, Clair, GC, Adkins, JN, Gore, S, Xia, G, Black, NS, Downing, T, O'Neill, E
et al (show 2 more authors) (2017) Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections. JOURNAL OF INFECTIOUS DISEASES, 215 (1). 80 - 87.

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Abstract

Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobial resistance crisis. We report a new approach to the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections by demonstrating that oxacillin can be used to significantly attenuate the virulence of MRSA despite the pathogen being resistant to this drug. Using mechanistic in vitro assays and in vivo models of invasive pneumonia and sepsis, we show that oxacillin-treated MRSA strains are significantly attenuated in virulence. This effect is based primarily on the oxacillin-dependent repression of the accessory gene regulator quorum-sensing system and altered cell wall architecture, which in turn lead to increased susceptibility to host killing of MRSA. Our data indicate that β-lactam antibiotics should be included in the treatment regimen as an adjunct antivirulence therapy for patients with MRSA infections. This would represent an important change to current clinical practice for treatment of MRSA infection, with the potential to significantly improve patient outcomes in a safe, cost-effective manner.

Item Type: Article
Uncontrolled Keywords: MRSA, antibiotic, beta-lactam, virulence, attenuation
Depositing User: Symplectic Admin
Date Deposited: 08 Jun 2017 09:24
Last Modified: 19 Feb 2021 11:59
DOI: 10.1093/infdis/jiw461
Open Access URL: https://academic.oup.com/jid/article-lookup/doi/10...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3007862