Eperezolid modulates autophagy to control the growth of intracellular mycobacteria

Abstract

The emergence of drug resistance Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) remains a significant threat to global health. Therefore, alternative host-directed strategies have been explored to combat the pathogen and boost anti-TB immunity inside the host. Among the host-directed therapies, autophagy, a well-established host mechanism, has been studied extensively to regulate the growth of mycobacteria. Hence, we mainly focus on the induction of autophagy by using pharmaceutical compounds to target the deadly disease. Our ongoing study analyzed the antimycobacterial effect of Eperezolid, a pharmacologically active compound from the LOPAC library. We dissected the non-cytotoxic dose of the compound via MTT assay, which was found to be 1µM. Further, time kinetics experiments were done to check the autophagic induction potential of the compound in dTHP-1 cells. We found the optimum conversion of LC3-I to LC3-II and more LC3 puncta formation after 24h of treatment. Similarly, MDC staining also signified more autophagic vacuole formation after 24h drug treatment. In addition, to check the effect of Eperezolid on the intracellular viability of mycobacteria, CFU assays were performed. We observed a sharp reduction in the viability of M. smegmatis in Eperezolid treated cells as compared to control cells which described its mycobacterial growth inhibition capacity. Further experiments are underway to deduce the autophagy induction potential of Eperezolid in mycobacteria-infected cells.