Azalomycin F<sub>5a</sub>, a 36-membered macrocyclic lactone isolated from several streptomyces strains, presented remarkable anti-methicillin-resistant Staphylococcus aureus (MRSA) activities. To improve ...Azalomycin F<sub>5a</sub>, 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<sub>5a</sub> in combination with vitamin K<sub>3</sub> were first evaluated using checkerboard assay. Then the minimal concentration inhibiting colony formation by 99% (MIC<sub>99</sub>) and mutant prevention concentration (MPC) of azalomycin F<sub>5a</sub> alone and in combination with vitamin K<sub>3</sub> 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<sub>5a</sub> in combination with vitamin K<sub>3</sub>. The mutant selection windows (MSWs, MIC<sub>99</sub>-MPC) of azalomycin F<sub>5a</sub> alone against MRSA tested were 2.07 - 6.40 μg/mL, and the MPCs of azalomycin F<sub>5a</sub> in combination with vitamin K<sub>3</sub> against MRSA tested were 1.60 - 3.20 μg/mL. These indicated that the MPCs of azalomycin F<sub>5a</sub> in combination could drop down to below its MIC<sub>99</sub> alone. According to the hypothesis of MSW, the narrower MSWs of azalomycin F<sub>5a </sub>alone, even closed MSWs in combination with vitamin K<sub>3</sub>, together with their synergistic anti-MRSA activities, indicated that azalomycin F<sub>5a </sub>had a good potential to develop as a new antimicrobial agent.展开更多
文摘Azalomycin F<sub>5a</sub>, 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<sub>5a</sub> in combination with vitamin K<sub>3</sub> were first evaluated using checkerboard assay. Then the minimal concentration inhibiting colony formation by 99% (MIC<sub>99</sub>) and mutant prevention concentration (MPC) of azalomycin F<sub>5a</sub> alone and in combination with vitamin K<sub>3</sub> 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<sub>5a</sub> in combination with vitamin K<sub>3</sub>. The mutant selection windows (MSWs, MIC<sub>99</sub>-MPC) of azalomycin F<sub>5a</sub> alone against MRSA tested were 2.07 - 6.40 μg/mL, and the MPCs of azalomycin F<sub>5a</sub> in combination with vitamin K<sub>3</sub> against MRSA tested were 1.60 - 3.20 μg/mL. These indicated that the MPCs of azalomycin F<sub>5a</sub> in combination could drop down to below its MIC<sub>99</sub> alone. According to the hypothesis of MSW, the narrower MSWs of azalomycin F<sub>5a </sub>alone, even closed MSWs in combination with vitamin K<sub>3</sub>, together with their synergistic anti-MRSA activities, indicated that azalomycin F<sub>5a </sub>had a good potential to develop as a new antimicrobial agent.
