Affiliation: 4382 Medical Sciences Building, Dept. of Medical Genetics and Microbiology, University of Toronto,1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Mycobacterial infections, including tuberculosis (TB) and leprosy, are infectious diseases of global importance. Control of TB is complicated by difficulties in administrating the long-course chemotherapy regimens, the inability to eliminate latent organisms, and the increasing appearance of multidrug resistant strains of Mycobacterium tuberculosis . New drugs for the control of TB are urgently needed, including developments of short-term antibiotic regimens to minimize the emergence of drug resistance and new drugs to treat MDR-TB patients and to eradicate the latent bacteria. Recent years have witnessed emergence of many new structural classes of antimycobacterial agents, some of which exhibit promising activities against susceptible and resistant strains of M. tuberculosis. In particular, the newly discovered diarylquinoline with superior antituberculous activity and encouraging results from recent studies of nitroimidazopyrans and oxazolidinones have generated considerable excitement. Genetic and biochemical studies, facilitated by the availability of mycobacterial genomes, have provided much insight into the biosynthesis of mycobacterial cell wall and metabolic processes unique to the pathogen, which reveal many potential drug targets. Some progresses toward targeting novel enzymes or biochemical processes have been made. This review summarizes these developments. Efforts to make use of existing drugs for treatment of TB, but which are currently marketed for controlling of other infections, are discussed. In addition, mechanisms of antibiotic resistance including the mycobacterial cell wall permeability barrier and novel resistance mechanisms are also discussed.