Usnic acid modifies MRSA drug resistance through down‐regulation of proteins involved in peptidoglycan and fatty acid biosynthesis. Issue 12 (30th September 2019)

• Record Type: Journal Article
• Authors: Sinha, Sneha; Gupta, Vivek Kumar; Kumar, Parmanand; Kumar, Rajiv; Joshi, Robin; Pal, Anirban; Darokar, Mahendra P.
• Is Part Of: FEBS open bio. Volume 9:Issue 12(2019)
• Page Start: 2025
• Page End: 2040
• Publication Date: 2019-09-30
• Subjects: drug resistance reversal -- MRSA -- phytomolecules -- Staphylococcus aureus -- synergy -- usnic acid; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12650
• Languages: English
• ISSNs: 2211-5463

Abstract

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. Abstract : This is the first report on the drug resistance‐modifying potential of usnic acid (UA) through inhibition of the multidrug resistance (MDR) efflux pump and down‐regulation of proteins involved in peptidoglycan and fatty acid biosynthesis. This compound may be helpful in the management of infection caused by MRSA through (a) lowering the prescribed amount of antibiotics, (b) decreasing MDR generation, and (c) intensifying the efficacy of antibiotics against MRSA/VRSA under both in vitro and in vivo conditions. These results may be helpful in the development of anti‐MRSA drug combinations from economical and non‐toxic natural products.