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- Title
Usnic acid modifies MRSA drug resistance through down‐regulation of proteins involved in peptidoglycan and fatty acid biosynthesis.
- Authors
Sinha, Sneha; Gupta, Vivek Kumar; Kumar, Parmanand; Kumar, Rajiv; Joshi, Robin; Pal, Anirban; Darokar, Mahendra P.
- Abstract
Multidrug‐resistant Staphylococcus aureus infections place a huge burden on the healthcare sector and the wider community. An increasing rate of infections caused by methicillin‐resistant Staphylococcus aureus (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 the 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.
- Subjects
NORFLOXACIN; DRUG resistance; METHICILLIN-resistant staphylococcus aureus; MUPIROCIN; STAPHYLOCOCCUS aureus infections; FATTY acids; BIOSYNTHESIS; MULTIDRUG resistance in bacteria
- Publication
FEBS Open Bio, 2019, Vol 9, Issue 12, p2025
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1002/2211-5463.12650