Author(s)

Xuejie Xu, Xuejiao Wu, Ganjun Yuan^*, Li Xu, Yimin Wang

College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang, China.

Azalomycin F_5a, a 36-membered macrocyclic lactone isolated from several streptomyces strains, presented remarkable anti-methicillin-resistant Staphylococcus aureus (MRSA) activities. To improve its anti-MRSA potential and to evaluate the probability of MRSA resistant to it before development, the anti-MRSA activities of azalomycin F_5a in combination with vitamin K₃ were first evaluated using checkerboard assay. Then the minimal concentration inhibiting colony formation by 99% (MIC₉₉) and mutant prevention concentration (MPC) of azalomycin F_5a alone and in combination with vitamin K₃ against MRSA were determined using agar plates with linear antimicrobial concentration decrease. The fractional inhibitory concentration indexes (FICIs) of 0.25 - 0.50 showed the synergistic activity of azalomycin F_5a in combination with vitamin K₃. The mutant selection windows (MSWs, MIC₉₉-MPC) of azalomycin F_5a alone against MRSA tested were 2.07 - 6.40 μg/mL, and the MPCs of azalomycin F_5a in combination with vitamin K₃ against MRSA tested were 1.60 - 3.20 μg/mL. These indicated that the MPCs of azalomycin F_5a in combination could drop down to below its MIC₉₉ alone. According to the hypothesis of MSW, the narrower MSWs of azalomycin F_5a alone, even closed MSWs in combination with vitamin K₃, together with their synergistic anti-MRSA activities, indicated that azalomycin F_5a had a good potential to develop as a new antimicrobial agent.

MRSA, Azalomycin F_5a, Mutant Selection Windows, Combination, Antibiotic Resistance

Xu, X. , Wu, X. , Yuan, G. , Xu, L. and Wang, Y. (2016) Mutant Selection Windows of Azalomycin F_5a in Combination with Vitamin K₃ against Methicillin-Resistant Staphylococcus aureus. Journal of Biosciences and Medicines, 4, 162-174. doi: 10.4236/jbm.2016.412020.