Lefamulin: A Novel Pleuromutilin Effective Against Mycobacterium tuberculosis via Efflux Inhibition

Tuberculosis (TB) remains a major global health challenge, exacerbated by the increasing prevalence of drug-resistant strains. Drug repurposing is a crucial strategy for TB control, particularly in combating resistance. Through this approach, the anti-TB potential of lefamulin was identified as a candidate for systemic administration. Lefamulin demonstrates potent inhibitory activity against Mycobacterium tuberculosis (M.tb) in vitro , in vivo, and within intracellular environments. Notably, it exhibits synergistic effects when combined with the first-line anti-TB drugs rifampicin and isoniazid, as demonstrated in insect model. Overall design: Logarithmic growth phase M.tb H37Rv cultures were incubated in 7H9 medium containing either 10× MIC of lefamulin (Lef group) or an equivalent volume of DMSO (control group). Following 7 hours of incubation, the cells were collected and lysed.