Biogenesis of the mycobacterial cell wall and the site of action of ethambutol.

Antimicrobial Agents and Chemotherapy
K MikusováP J Brennan

Abstract

The effect of ethambutol (EMB) is primarily on polymerization steps in the biosynthesis of the arabinan component of cell wall arabinogalactan (AG) of Mycobacterium smegmatis. Inhibition of the synthesis of the arabinan of lipoarabinomannan (LAM) occurred later, and thus in the cases of AG and LAM, the polymerization of D-arabinofuranose apparently involves separate pathways. While the synthesis of these arabinans was normal in an EMB-resistant isogeneic strain, the addition of EMB to the resistant strain resulted in partial inhibition of the synthesis of the arabinan of LAM and the emergence of a novel, truncated form of LAM, indicating partial susceptibility of the resistant gene(s) and providing a new intermediate in the LAM biosynthetic sequence. A consequence of inhibition of AG arabinan biosynthesis is the lack of new sites for mycolate attachment and thus the channeling of mycolate residues into a variety of free lipids which then accumulate. The primary biochemical effects of EMB can be explained by postulating separate AG and LAM pathways catalyzed by a variety of extramembranous arabinosyl transferases with various degrees of sensitivity to EMB.

References

Aug 1, 1979·Antimicrobial Agents and Chemotherapy·K TakayamaJ O Kilburn
Feb 1, 1990·Journal of Bacteriology·G R HirschfieldP J Brennan
Sep 1, 1989·Antimicrobial Agents and Chemotherapy·K Takayama, J O Kilburn
Jul 1, 1985·Antimicrobial Agents and Chemotherapy·L G PaulinH J Pösö
Jan 1, 1971·Pure and Applied Chemistry. Chimie Pure Et Appliquée·E Lederer
Jan 1, 1995·Annual Review of Biochemistry·P J Brennan, H Nikaido
Mar 1, 1995·Antimicrobial Agents and Chemotherapy·L DengM R McNeil
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·G S BesraK Takayama
Jul 1, 1993·Antimicrobial Agents and Chemotherapy·G SilveG Laneelle

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Citations

Sep 25, 2004·Medicinal Research Reviews·Rama P TripathiVinod K Tiwari
Nov 29, 2007·Pflügers Archiv : European journal of physiology·David AlsteensYves F Dufrêne
Jul 1, 1996·Trends in Microbiology·C E Barry, K Mdluli
Jan 7, 1998·Biochemical Pharmacology·C E Barry
May 27, 2003·Biochimie·Jérôme NigouGermain Puzo
Feb 1, 1997·International Journal of Antimicrobial Agents·B Heym, S T Cole
Dec 14, 1999·International Journal of Antimicrobial Agents·B Petrini, S Hoffner
Nov 18, 1998·Current Opinion in Structural Biology·B J Mengeling, S J Turco
Sep 10, 2002·Bioorganic & Medicinal Chemistry Letters·Ashish K PathakRobert C Reynolds
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·J A MaddryR C Reynolds
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·J D AyersG S Besra
Dec 28, 1999·Microbes and Infection·G R Strohmeier, M J Fenton
Jul 17, 1998·Current Opinion in Chemical Biology·D Chatterjee
Apr 6, 2011·Analytical Chemistry·Benjamin G HawkinsBrian J Kirby
Feb 16, 2008·Journal of Proteome Research·Rong Wang, Edward M Marcotte
Mar 11, 2008·Nature Reviews. Microbiology·Christopher Weidenmaier, Andreas Peschel
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Helen L BirchGurdyal S Besra
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·A E BelangerJ M Inamine
Aug 6, 2009·Glycobiology·Henrieta SkovierováMary Jackson
Apr 30, 2010·The Journal of Antimicrobial Chemotherapy·Claudia PlinkeStefan Niemann
Dec 7, 2013·Science Translational Medicine·Srinivasa P S RaoUjjini H Manjunatha
Jul 15, 2009·Antimicrobial Agents and Chemotherapy·R GoudeT Parish
Jan 22, 2013·Antimicrobial Agents and Chemotherapy·Jansy SarathyMartin Gengenbacher
Oct 27, 2004·Antimicrobial Agents and Chemotherapy·Ann S G LeeSin Yew Wong
Jul 6, 2012·Clinical Microbiology Reviews·Barbara A Brown-ElliottRichard J Wallace
Dec 7, 2007·Journal of Bacteriology·Martina BelánováKatarína Mikusová
Mar 7, 2008·Microbiology and Molecular Biology Reviews : MMBR·Erik C Hett, Eric J Rubin
Jul 12, 2013·Future Microbiology·Mary JacksonPatrick J Brennan
Mar 17, 2016·Advances in Bioinformatics·N HarathiSuresh Kumar Chitta
Aug 4, 2011·Expert Review of Anti-infective Therapy·Yuliya Yasinskaya, Leonard Sacks

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