QcrB inhibitor Q203 (Telacebec) can synergize with clofazimine and clarithromycin to control a Mycobacterium avium infection.

Abstract

The targeting of the mycobacterial electron transport chain for drug development has recently garnered significant clinical success. The cytochrome bcc complex within the electron transport chain has emerged as a viable drug target, with the antibiotic Q203 (Telacebec) showing excellent activity against M. tuberculosis in vitro and in vivo. To determine if Q203 can function as an antibiotic against the non-tuberculosis mycobacteria M. avium and M. intracellulare (MAC), MIC and bactericidal studies were performed, both against various laboratory and clinical strains of MAC as well as in vivo infection studies. These studies found that Q203 provides synergistic activity against all tested MAC isolates when combined with clarithromycin and provided significant added benefit in a acute M. avium mouse infection model when combined with clarithromycin and clofazimine.