Bipolar Distribution of Minimum Inhibitory Concentration of Q203 Across Mycobacterial Species.

In this study, we conducted an experimental study to evaluate susceptibility of Q203 against , as well as the major pathogenic nontuberculous mycobacterial species. A total of 344 nonduplicate mycobacterium isolates were randomly selected for susceptibility testing. Overall, Q203 exhibited excellent activity against multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) isolates, whereas it showed high minimum inhibitory concentration (MIC) values for all nontuberculous mycobacteria (NTM) isolates tested. The MIC and MIC values were both 0.008 mg/L for MDR- and XDR-TB isolates, respectively. In contrast, the MIC and MIC values of four NTM species were all >16 mg/L. QcrB of , a component of the CytBC1 complex of the respiratory chain targeted by Q230, shared 89.7% amino acid sequence identity with QcrB, 87.9% with that of , and 84.0% with that of , whereas with low sequence identity observed in QcrB sequence of . Notably, the QcrBs of and contained a 10-amino acid insertion in the linker between the eighth and ninth helical region. In conclusion, our data demonstrate the bipolar distribution of Q203 MICs across mycobacterial species. Compared with the high MICs in four clinically relevant mycobacterial species, MDR- and XDR-TB isolates have extremely low MICs, indicating that Q203 is a particularly promising candidate for TB treatment. In addition, the 10-amino acid insertion within QcrBs of and may be a plausible explanation for the natural resistance to Q203 among these two species.