title: Targeting the mycobacterial envelope for tuberculosis drug development.
abstract: The bacterium that causes tuberculosis, Mycobacterium tuberculosis, possesses a rather unique outer membrane composed largely of lipids that possess long-chain and branched fatty acids, called mycolic acids. These lipids form a permeability barrier that prevents entry of many environmental solutes, thereby making these bacteria acid-fast and able to survive extremely hostile surroundings. Antitubercular drugs must penetrate this layer to reach their target. This review highlights drug development efforts that have added to the slowly growing tuberculosis drug pipeline, identified new enzyme activities to target with drugs and increased the understanding of important biosynthetic pathways for mycobacterial outer membrane and cell wall core assembly. In addition, a portion of this review looks at discovery efforts aimed at weakening this barrier to decrease mycobacterial virulence, decrease fitness in the host or enhance the efficacy of the current drug repertoire by disrupting the permeability barrier.
authors.affiliation: Department of Chemistry, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Favrot
authors.forename: Donald R
authors.initials: DR
authors.lastname: Ronning
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000472:pathogenicity; D009171:Mycolic Acids / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy; D014774:Virulence
chemical_list: D000995:Antitubercular Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D009171:Mycolic Acids