Usnic acid modifies modifies MRSA drug resistance through down-regulation of proteins involved in peptidoglycan and fatty acid biosynthesis.
FEBS Open Bio. 2019 May 03;:
Authors: Sinha S, Gupta VK, Kumar P, Kumar R, Joshi R, Pal A, Darokar MP
Multidrug-resistant Staphylococcus aureus infections place a huge burden on the healthcare sector and the wider community. An increasing rate of infections caused by MRSA has necessitated the development of alternative agents. We previously reported that usnic acid (UA) has activity against MRSA; here, we report the effect of UA in combination with norfloxacin on the drug resistance of MRSA clinical isolates. We observed that the combination of UA-norfloxacin significantly reduces bacterial burden in mouse models infected with S. aureus, without causing any detectable associated toxicity. Proteomic analysis indicated that UA-norfloxacin induces oxidative stress within cells, which leads to membrane damage and inhibits metabolic activity and biosynthesis of peptidoglycan and fatty acids. Collectively, this study provides evidence that UA in combination with norfloxacin may be a potential candidate for development into a resistance-modifying agent for the treatment of invasive MRSA infections.
PMID: 31050202 [PubMed - as supplied by publisher]