Structure, function and biosynthesis of the Mycobacterium tuberculosis cell wall:: arabinogalactan and lipoarabinomannan assembly with a view to discovering new drug targets

被引:60
作者
Alderwick, L. J.
Birch, H. L.
Mishra, A. K.
Eggeling, L.
Besra, G. S. [1 ]
机构
[1] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England
[2] Res Ctr Julich, Inst Biotechnol 1, D-52425 Julich, Germany
基金
英国医学研究理事会; 英国惠康基金;
关键词
arabinogalactan; cell wall; drug target; lipoarabinomannan; Mycobocterium tuberculosis;
D O I
10.1042/BST0351325
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
in spite of effective antibiotics to treat TB (tuberculosis) since the early 1960s, we enter the new millennium with TB, currently the leading cause of death from a single infectious agent, killing more than three million people worldwide each year. Thus an understanding of drug-resistance mechanisms, the immunobiology of cell wall components to elucidate host-pathogen interactions and the discovery of new drug targets are now required for the treatment of TB. Above the plasma membrane is a classical chemotype IV PG (peptidoglycan) to which is attached the macromolecular structure, mycolyl-arabinogalactan, via a unique diglycosylphosphoryl bridge. This review will discuss the assembly of the mAGP (mycolyl-arabinogalactan-peptidoglycan), its associated glycolipids and the site of action of EMB (ethambutol), bringing forward a new era in TB research and focus on new drugs to combat multidrug resistant TB.
引用
收藏
页码:1325 / 1328
页数:4
相关论文
共 48 条
[1]
Deletion of Cg-emb in corynebacterianeae leads to a novel truncated cell wall arabinogalactan, whereas inactivation of Cg-ubiA results in an Arabinan-deficient mutant with a cell wall galactan core [J].
Alderwick, LJ ;
Radmacher, E ;
Seidel, M ;
Gande, R ;
Hitchen, PG ;
Morris, HR ;
Dell, A ;
Sahm, H ;
Eggeling, L ;
Besra, GS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (37) :32362-32371
[2]
Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall Arabinan biosynthesis in Mycobacterium tuberculosis [J].
Alderwick, Luke J. ;
Seidel, Mathias ;
Sahm, Hermann ;
Besra, Gurdyal S. ;
Eggeling, Lothar .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (23) :15653-15661
[3]
In vivo interaction between the polyprenol phosphate mannose synthase Ppm1 and the integral membrane protein Ppm2 from Mycobacterium smegmatis revealed by a bacterial two-hybrid system [J].
Baulard, AR ;
Gurcha, SS ;
Engohang-Ndong, J ;
Gouffi, K ;
Locht, C ;
Besra, GS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (04) :2242-2248
[4]
The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol [J].
Belanger, AE ;
Besra, GS ;
Ford, ME ;
Mikusova, K ;
Belisle, JT ;
Brennan, PJ ;
Inamine, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (21) :11919-11924
[5]
Roles of conserved proline and glycosyltransferase motifs of embC in biosynthesis of lipoarabinomannan [J].
Berg, S ;
Starbuck, J ;
Torrelles, JB ;
Vissa, VD ;
Crick, DC ;
Chatterjee, D ;
Brennan, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (07) :5651-5663
[6]
Biosynthesis of mycobacterial lipoarabinomannan [J].
Besra, GS ;
Morehouse, CB ;
Rittner, CM ;
Waechter, CJ ;
Brennan, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (29) :18460-18466
[7]
Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response [J].
Briken, V ;
Porcelli, SA ;
Besra, GS ;
Kremer, L .
MOLECULAR MICROBIOLOGY, 2004, 53 (02) :391-403
[8]
CHATTERJEE D, 1992, J BIOL CHEM, V267, P6234
[9]
Genetic basis for the synthesis of the immunomodulatory mannose caps of lipoarabinomannan in Mycobacterium tuberculosis [J].
Dinadayala, Premkumar ;
Kaur, Devinder ;
Berg, Stefan ;
Amin, Anita G. ;
Vissa, Varalakshmi D. ;
Chatterjee, Delphi ;
Brennan, Patrick J. ;
Crick, Dean C. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (29) :20027-20035
[10]
Comparative cell wall core biosynthesis in the mycolated pathogens, Mycobacterium tuberculosis and Corynebacterium diphtheriae [J].
Dover, LG ;
Cerdeño-Tárraga, AM ;
Pallen, MJ ;
Parkhill, J ;
Besra, GS .
FEMS MICROBIOLOGY REVIEWS, 2004, 28 (02) :225-250