title: Progress in targeting cell envelope biogenesis in Mycobacterium tuberculosis.
abstract: Most of the newly discovered compounds showing promise for the treatment of TB, notably multidrug-resistant TB, inhibit aspects of Mycobacterium tuberculosis cell envelope metabolism. This review reflects on the evolution of the knowledge that many of the front-line and emerging products inhibit aspects of cell envelope metabolism and in the process are bactericidal not only against actively replicating M. tuberculosis, but contrary to earlier impressions, are effective against latent forms of the disease. While mycolic acid and arabinogalactan synthesis are still primary targets of existing and new drugs, peptidoglycan synthesis, transport mechanisms and the synthesis of the decaprenyl-phosphate carrier lipid all show considerable promise as targets for new products, older drugs and new combinations. The advantages of whole cell- versus target-based screening in the perpetual search for new targets and products to counter multidrug-resistant TB are discussed.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA. mary.jackson@colostate.edu
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
authors.forename: Michael R
authors.initials: MR
authors.lastname: McNeil
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Brennan
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents