Abstract
Azalomycin F5a, 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 F5a 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 F5a 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 F5a in combination with vitamin K3. The mutant selection windows (MSWs, MIC99-MPC) of azalomycin F5a alone against MRSA tested were 2.07 - 6.40 μg/mL, and the MPCs of azalomycin F5a in combination with vitamin K3 against MRSA tested were 1.60 - 3.20 μg/mL. These indicated that the MPCs of azalomycin F5a in combination could drop down to below its MIC99 alone. According to the hypothesis of MSW, the narrower MSWs of azalomycin F5a alone, even closed MSWs in combination with vitamin K3, together with their synergistic anti-MRSA activities, indicated that azalomycin F5a had a good potential to develop as a new antimicrobial agent.
Highlights
Xu et al 164 methicillin-resistant Staphylococcus aureus (MRSA) activities, together with those of vitamin K3, were evaluated by us [13] [14], and the results showed that azalomycin F5a and vitamin K3 had remarkable anti-MRSA activities
Checkerboard test showed that all the fractional inhibitory concentration indexes (FICIs) of azalomycin F5a in combination with vitamin K3 against MRSA strains tested were 0.25 - 0.50 (Table 1)
This indicated that azalomycin F5a combined with vitamin K3 presented synergistic anti-MRSA activities
Summary
The hypotheses of mutant prevention concentration (MPC) and mutant selection window (MSW) were put forward [3] [4] [5] These theories suggested that the antimicrobial concentration should avoid falling within MSW to prevent resistant mutant, and an antimicrobial concentration above its MPC would rarely enrich the growth of resistant subpopulations. As it is unavoidable for the antimicrobial concentration to drop down to below MPC, the narrower the MSW of antibiotics against pathogenic bacteria is, the less the probability of pathogenic bacteria being resistant to it is.
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