Targeting the mycobacterial envelope for tuberculosis drug development

Lorenza Favrot, Donald R. Ronning

Research output: Contribution to journalReview article

59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1023-1036
Number of pages14
JournalExpert Review of Anti-Infective Therapy
Volume10
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • 7-amino-4-methylcoumarin
  • BTZ043
  • CD117
  • CD39
  • DNB
  • OPC-67683
  • PA-824
  • SQ109
  • arabinogalactan
  • cell wall
  • clavulanic acid
  • ethambutol
  • ethionamide
  • isoniazid
  • meropenum
  • mycobacterial outer membrane
  • mycolic acids
  • potentiation
  • pyrazinamide
  • rifampicin
  • triclosan
  • tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Virology
  • Infectious Diseases

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