Sterilizing Effects of Novel Regimens Containing TB47, Clofazimine, and Linezolid in a Murine Model of Tuberculosis
Wei Yu, Buhari Yusuf, Shuai Wang, Xirong Tian, H. M. Adnan Hameed, Zhili Lu, Gift Chiwala, Md Shah Alam, Gregory M. Cook, Dmitry A. Maslov, Nanshan Zhong, Tianyu Zhang
Abstract
TB47, a new drug candidate targeting QcrB in the electron transport chain, has shown a unique synergistic activity with clofazimine and forms a highly sterilizing combination. Here, we investigated the sterilizing effects of several all-oral regimens containing TB47 plus clofazimine and linezolid as a block and the roles of fluoroquinolones and pyrazinamide in them. All these regimens cured tuberculosis within 4 to 6 months in a well-established mouse model, and adding pyrazinamide showed a significant difference in bactericidal effects.
Topics & Concepts
ClofaziminePyrazinamideLinezolidTuberculosisPharmacologyBedaquilineMedicineAntibacterial agentMicrobiologyAntibioticsRifampicinChemistryMycobacterium tuberculosisBiologyLeprosyImmunologyBacteriaVancomycinPathologyStaphylococcus aureusGeneticsTuberculosis Research and EpidemiologyMycobacterium research and diagnosisAntibiotic Resistance in Bacteria