A new plant-derived antibacterial is an inhibitor of efflux pumps in Staphylococcus aureus
Shiu, W.K.P. and Malkinson, J.P. and Rahman, M.M. and Curry, J. and Stapleton, P. and Gunaratnam, M. and Neidle, S. and Mushtaq, S. and Warner, M. and Livermore, D.M. and Evangelopoulos, Dimitrios and Basavannacharya, Chandrakala and Bhakta, Sanjib and Schindler, B.D. and Seo, S.M. and Coleman, D. and Kaatz, G.W. and Gibbons, S. (2013) A new plant-derived antibacterial is an inhibitor of efflux pumps in Staphylococcus aureus. International Journal of Antimicrobial Agents 42 (6), pp. 513-518. ISSN 0924-8579.
Abstract
An in-depth evaluation was undertaken of a new antibacterial natural product (1) recently isolated and characterised from the plant Hypericum olympicum L. cf. uniflorum. Minimum inhibitory concentrations (MICs) were determined for a panel of bacteria, including: meticillin-resistant and -susceptible strains of Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus; vancomycin-resistant and -susceptible Enterococcus faecalis and Enterococcus faecium; penicillin-resistant and -susceptible Streptococcus pneumoniae; group A streptococci (Streptococcus pyogenes); and Clostridium difficile. MICs were 2–8 mg/L for most staphylococci and all enterococci, but were ≥16 mg/L for S. haemolyticus and were >32 mg/L for all species in the presence of blood. Compound 1 was also tested against Gram-negative bacteria, including Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium but was inactive. The MIC for Mycobacterium bovis BCG was 60 mg/L, and compound 1 inhibited the ATP-dependent Mycobacterium tuberculosis MurE ligase [50% inhibitory concentration (IC50) = 75 μM]. In a radiometric accumulation assay with a strain of S. aureus overexpressing the NorA multidrug efflux pump, the presence of compound 1 increased accumulation of 14C-enoxacin in a concentration-dependent manner, implying inhibition of efflux. Only moderate cytotoxicity was observed, with IC50 values of 12.5, 10.5 and 8.9 μM against human breast, lung and fibroblast cell lines, respectively, highlighting the potential value of this chemotype as a new antibacterial agent and efflux pump inhibitor.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | Hypericum olympicum, Olympicin A, Staphylococcus aureus, MurE ligase |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 04 Oct 2013 10:36 |
| Last Modified: | 02 Aug 2023 17:07 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/8360 |
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