Targeting the formation of the cell wall core of M. tuberculosis.
Mycobacteria have a unique cell wall, which is rich in drug targets. The cell wall core consists of a peptidoglycan layer, a mycolic acid layer, and an arabinogalactan polysaccharide connecting them. The detailed structure of the cell wall core is largely, although not completely, understood and will be presented. The biosynthetic pathways of all three components reveal significant drug targets that are the basis of present drugs and/or have potential for new drugs. These pathways will be reviewed and include enzymes involved in polyisoprene biosynthesis, soluble arabinogalactan precursor production, arabinogalactan polymerization, fatty acid synthesis, mycolate maturation, and soluble peptidoglycan precursor formation. Information relevant to targeting all these enzymes will be presented in tabular form. Selected enzymes will then be discussed in more detail. It is thus hoped this chapter will aid in the selection of targets for new drugs to combat tuberculosis.
Barry
Clifton E
CE
Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, NIAID, NIH, 33 North Drive Bldg 33, Room 2W20D Bethesda, MD 20892, USA.
Crick
Dean C
DC
McNeil
Michael R
MR
D000995:Antitubercular Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D005685:Galactans / Q000096:biosynthesis; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism*; D009171:Mycolic Acids / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis; D011106:Polyisoprenyl Phosphates / Q000096:biosynthesis
D000995:Antitubercular Agents; D005685:Galactans; D009171:Mycolic Acids; D010457:Peptidoglycan; D011106:Polyisoprenyl Phosphates; C068697:decaprenyl phosphate; C005653:arabinogalactan