Comparative mycobacterial genomics as a tool for drug target and antigen discovery

被引:52
作者
Cole, ST [1 ]
机构
[1] Inst Pasteur, Unite Genet Mol Bacterienne, F-75724 Paris 15, France
关键词
drug targets; functional genomics; genomics; leprosy; tuberculosis;
D O I
10.1183/09031936.02.00400202
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Genomics and the associated downstream technologies are generating vast data sets that provide new opportunities for understanding and combating both infectious and genetic diseases in humans. The genomic approach has been applied to tuberculosis, a major cause of transmissible morbidity and mortality, with notable success. Complete genome sequences are now available for three members of the Mycobacterium tuberculosis complex and the related intracellular pathogen M. leprae. Many of the predictions generated in silico by genomics have been validated through functional analysis, including studies of the transcriptome and proteome, and led to the identification of essential genes. Knowledge of the latter defines potential targets for new and existing drugs and their specificity can be assessed by comparative genomics with the host or other pathogens. Genomics is also furthering tuberculosis vaccine development by pinpointing potentially antigenic proteins as well as providing better diagnostic tools to detect infection.
引用
收藏
页码:78S / 86S
页数:9
相关论文
共 79 条
[1]   Identification of differentially expressed mRNA in prokaryotic organisms by customized amplification libraries (DECAL):: The effect of isoniazid on gene expression in Mycobacterium tuberculosis [J].
Alland, D ;
Kramnik, I ;
Weisbrod, TR ;
Otsubo, L ;
Cerny, R ;
Miller, LP ;
Jacobs, WR ;
Bloom, BR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (22) :13227-13232
[2]   Host responses and antigens involved in protective immunity to Mycobacterium tuberculosis [J].
Andersen, P .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1997, 45 (02) :115-131
[3]   Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes [J].
Argyrou, A ;
Blanchard, JS .
BIOCHEMISTRY, 2001, 40 (38) :11353-11363
[4]   A genome-based approach for the identification of essential bacterial genes [J].
Arigoni, F ;
Talabot, F ;
Peitsch, M ;
Edgerton, MD ;
Meldrum, E ;
Allet, E ;
Fish, R ;
Jamotte, T ;
Curchod, ML ;
Loferer, H .
NATURE BIOTECHNOLOGY, 1998, 16 (09) :851-856
[5]   CLONING OF AN MYCOBACTERIUM-TUBERCULOSIS DNA FRAGMENT ASSOCIATED WITH ENTRY AND SURVIVAL INSIDE CELLS [J].
ARRUDA, S ;
BOMFIM, G ;
KNIGHTS, R ;
HUIMABYRON, T ;
RILEY, LW .
SCIENCE, 1993, 261 (5127) :1454-1457
[6]   Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis [J].
Baldwin, SL ;
D'Souza, C ;
Roberts, AD ;
Kelly, BP ;
Frank, AA ;
Lui, MA ;
Ulmer, JB ;
Huygen, K ;
McMurray, DM ;
Orme, IM .
INFECTION AND IMMUNITY, 1998, 66 (06) :2951-2959
[7]   Conditionally replicating mycobacteriophages: A system for transposon delivery to Mycobacterium tuberculosis [J].
Bardarov, S ;
Kriakov, J ;
Carriere, C ;
Yu, SW ;
Vaamonde, C ;
McAdam, RA ;
Bloom, BR ;
Hatfull, GF ;
Jacobs, WR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10961-10966
[8]   Comparative genomics of BCG vaccines by whole-genome DNA microarray [J].
Behr, MA ;
Wilson, MA ;
Gill, WP ;
Salamon, H ;
Schoolnik, GK ;
Rane, S ;
Small, PM .
SCIENCE, 1999, 284 (5419) :1520-1523
[9]   Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis [J].
Belisle, JT ;
Vissa, VD ;
Sievert, T ;
Takayama, K ;
Brennan, PJ ;
Besra, GS .
SCIENCE, 1997, 276 (5317) :1420-1422
[10]   The Tat protein export pathway [J].
Berks, BC ;
Sargent, F ;
Palmer, T .
MOLECULAR MICROBIOLOGY, 2000, 35 (02) :260-274