Imatinib-Sensitive Tyrosine Kinases Regulate Mycobacterial Pathogenesis and Represent Therapeutic Targets against Tuberculosis

摘要: The lengthy course of treatment with currently used antimycobacterial drugs and the resulting emergence drug-resistant strains have intensified need for alternative therapies against Mycobacterium tuberculosis (Mtb), etiologic agent tuberculosis. We show that Mtb marinum use ABL related tyrosine kinases entry intracellular survival in macrophages. In mice, family kinase inhibitor, imatinib (Gleevec), when administered prophylactically or therapeutically, reduced both number granulomatous lesions bacterial load infected organs was also effective a rifampicin-resistant strain. Further, coadministered current first-line drugs, rifampicin rifabutin, acted synergistically. These data implicate host mycobacteria suggest may therapeutic efficacy Mtb. Because targets host, it is less likely to engender resistance compared conventional antibiotics decrease development drugs.