Potentiation effects by usnic acid in combination with antibiotics on clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA)
- 78 Downloads
The in vitro antibacterial activities of usnic acid (UA) in combination with six currently available antibiotics were evaluated through checkerboard microdilution and dynamic time-killing assays against Staphylococcus aureus and 10 clinical isolates of methicillin-resistant S. aureus (MRSA). The six antibiotics include three aminoglycosides (i.e., amikacin (AK), etimicin (EM), streptomycin (SM)), two glycopeptides (i.e., teicoplanin (TP), vancomycin (VA)) and a tetracycline (i.e., minocycline (MC)). UA alone showed MIC of 16 μg/mL against both S. aureus and MRSA strains. The checkerboard assay showed the range of fractional inhibitory indices (FICIs) as 0.156–1.500 against all the pathogens when UA was used in combination with the antibiotics. Significant bacteriostatic interactions of UA with TP and MC were observed. The enhancement of antibacterial activities against the tested pathogens were revealed by the bacteriostatic dose reduction indices (DRIs) ranges at 1–64 of UA and 1–32 of the antibiotics, especially the synergy of UA with TP by 90% and additive effects with VA by 50% isolates of MRSA strains, respectively. MC also showed 60% strains of synergy with UA. The time-killing curves further confirmed the bactericidal synergy among the combinations of UA with TP, AK, EM, and SM (1 × MIC, △LC24 = 3.406–4.344 log10CFU/mL) against one of the 10 MRSA strains, respectively. Other combinations showed additive effects or indifferences, while no antagonism occurred in all the tested combinations. The anti-MRSA potentiation is promising for further investigations in order to form a possible scenario of UA/antibiotics combinatory chemotherapy which would reduce their dosages and toxicological responses.
KeywordsAnti-MRSA activity Usnic acid Synergy Glycopeptides Minocycline
This work was supported by the National Natural Science Foundation of China (NSFC 81173504) and the supporting fund of Yunnan Province of China (2008PY001).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Clinical and Laboratory Standards Institute (2012) Table 2C. Zone diameter and MIC interpretive standards for Staphylococcus spp. performance standards for antimicrobial susceptibility testing. Twenty Second Informational Supplement. CLSI, Wayne, PA Approved Standard M100–S22Google Scholar
- Ferraz-Carvalho RS, Pereira MA, Linhares LA, Lira-Nogueira MC, Cavalcanti IM, Santos-Magalhaes NS, Montenegro LM (2016) Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates. Mem Inst Oswaldo Cruz 111:330–334CrossRefPubMedPubMedCentralGoogle Scholar
- Nanjing University of Traditional Chinese Medicine (NUTCM) (ed) (2005) Dictionary of Chinese crude drugs. second ed. Shanghai Scientific Technologic Publisher, Shanghai, China, pp 1815–1816Google Scholar
- Segatore B, Bellio P, Setacci D, Brisdelli F, Piovano M, Garbarino JA, Nicoletti M, Amicosante G, Perilli M, Celenza G (2012) In vitro interaction of usnic acid in combination with antimicrobial agents against methicillin-resistant Staphylococcus aureus clinical isolates determined by FICI and DeltaE model methods. Phytomedicine 19:341–347CrossRefPubMedGoogle Scholar