title: Molecular biology of drug resistance in Mycobacterium tuberculosis.
abstract: Tuberculosis (TB) has become a curable disease, thanks to the discovery of antibiotics. However, it has remained one of the most difficult infections to treat. Most current TB regimens consist of 6-9 months of daily doses of four drugs that are highly toxic to patients. The purpose of these lengthy treatments is to completely eradicate Mycobacterium tuberculosis, notorious for its ability to resist most antibacterial agents, thereby preventing the formation of drug resistant mutants. On the contrary, the prolonged therapies have led to poor patient adherence. This, together with a severe limit of drug choices, has resulted in the emergence of strains that are increasingly resistant to the few available antibiotics. Here, we review our current understanding of molecular mechanisms underlying the profound drug resistance of M. tuberculosis. This knowledge is essential for the development of more effective antibiotics, which are not only potent against drug resistant M. tuberculosis strains but also help shorten the current treatment courses required for drug susceptible TB.
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
authors.forename: Tasha
authors.initials: T
authors.lastname: Smith
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: Wolff
authors.forename: Liem
authors.initials: L
authors.lastname: Nguyen
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D001692:Biological Transport; D001711:Biotransformation; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression; D019450:Genes, MDR; D056084:Genetic Fitness; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D010349:Patient Compliance; D011718:Pyrazinamide / Q000627:therapeutic use*; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide