PreprintArticleVersion 1This version is not peer-reviewed
Mechanistic Insight into the Antimicrobial Mode of Action of Usnic Acid and Its Synergy with Norfloxacin against Methicillin-Resistant Staphylococcus aureus
Version 1
: Received: 29 July 2024 / Approved: 29 July 2024 / Online: 29 July 2024 (16:33:46 CEST)
How to cite:
Gangwar, B.; Kumar, S.; Kumar, P.; Pal, A.; Darokar, M. P. Mechanistic Insight into the Antimicrobial Mode of Action of Usnic Acid and Its Synergy with Norfloxacin against Methicillin-Resistant Staphylococcus aureus. Preprints2024, 2024072326. https://doi.org/10.20944/preprints202407.2326.v1
Gangwar, B.; Kumar, S.; Kumar, P.; Pal, A.; Darokar, M. P. Mechanistic Insight into the Antimicrobial Mode of Action of Usnic Acid and Its Synergy with Norfloxacin against Methicillin-Resistant Staphylococcus aureus. Preprints 2024, 2024072326. https://doi.org/10.20944/preprints202407.2326.v1
Gangwar, B.; Kumar, S.; Kumar, P.; Pal, A.; Darokar, M. P. Mechanistic Insight into the Antimicrobial Mode of Action of Usnic Acid and Its Synergy with Norfloxacin against Methicillin-Resistant Staphylococcus aureus. Preprints2024, 2024072326. https://doi.org/10.20944/preprints202407.2326.v1
APA Style
Gangwar, B., Kumar, S., Kumar, P., Pal, A., & Darokar, M. P. (2024). Mechanistic Insight into the Antimicrobial Mode of Action of Usnic Acid and Its Synergy with Norfloxacin against Methicillin-Resistant Staphylococcus aureus. Preprints. https://doi.org/10.20944/preprints202407.2326.v1
Chicago/Turabian Style
Gangwar, B., Anirban Pal and Mahendra P. Darokar. 2024 "Mechanistic Insight into the Antimicrobial Mode of Action of Usnic Acid and Its Synergy with Norfloxacin against Methicillin-Resistant Staphylococcus aureus" Preprints. https://doi.org/10.20944/preprints202407.2326.v1
Abstract
In this study, global response analysis was performed to explore the mechanism of action of Usnic acid and its synergy with Norfloxacin, a well-known quinolone antibiotic to which MRSA clinical isolates showed resistance (MIC, 500 µg/mL). Microdilution assay, growth kinetics, microscopic analysis, and cell-based assays consistently showed that Usnic acid possess strong anti-staphylococcal activity (MIC, 7.8 µg/ml), causes cell leakage, modulates efflux pump activity, and synergizes with Norfloxacin against multi-drug resistant clinical isolate MRSA 2071. Whole cell proteome profiling using gel-free based nano-LC-ESI-QTOF-MS/MS revealed several proteins whose expression was significantly modulated by Usnic acid and Norfloxacin alone or in combination. Usnic acid downregulated the abundance of RNA polymerase subunits (RpoB, RpoC), carbamoyl phosphate synthase large subunit (PyrAB), chaperone (GroEL), and adenylosuccinate synthetase (PurA). Interestingly, proteins found to be upregulated in the presence of Usnic acid and Norfloxacin included oxidative stress-related proteins such as peroxidase (Tpx), alkyl hydroperoxide reductase (AphC), and general stress protein (UspA). This study clearly showed that Usnic acid affects numerous cellular targets and can potentiate the action of Norfloxacin. Furthermore, an in-vivo study emphasized the use of Usnic acid to develop as a safe phytopharmaceutical to repurpose old antibiotics through combination therapy against MRSA infections.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
