Identifying Vulnerable Pathways in Mycobacterium tuberculosis by Using a Knockdown Approach

被引：66

作者：

Carroll, Paul ^{[1
]}

Faray-Kele, Marie-Claire ^{[1
]}

Parish, Tanya ^{[1
,2
]}

机构：

[1] Queen Mary Univ London, London E1 2AT, England

[2] Infect Dis Res Inst, Seattle, WA 98104 USA

来源：

APPLIED AND ENVIRONMENTAL MICROBIOLOGY | 2011年 / 77卷 / 14期

关键词：

GLUTAMINE-SYNTHETASE; DRUG TARGETS; EXPRESSION; GLNA1;

D O I：

10.1128/AEM.02880-10

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

We constructed recombinant strains of Mycobacterium tuberculosis in which expression of specific genes was downregulated to identify vulnerable drug targets. Growth phenotypes in macrophages and culture were used to rank targets: the dprE1, clpP1, and fadD32 operons were the best targets and glnA1, glnE, pknL, regX3, and senX3 were poor targets.

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收藏

页码：5040 / 5043

页数：4

相关论文

共 14 条

[1]

Potential drug targets in Mycobacterium tuberculosis through metabolic pathway analysis [J].

Anishetty, S ;

Pulimi, M ;

Pennathur, G .

COMPUTATIONAL BIOLOGY AND CHEMISTRY, 2005, 29 (05) :368-378

[2]

The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism -: Novel insights into drug mechanisms of action [J].

Boshoff, HIM ;

Myers, TG ;

Copp, BR ;

McNeil, MR ;

Wilson, MA ;

Barry, CE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (38) :40174-40184

[3]

Use of a tetracycline-inducible system for conditional expression in Mycobacterium tuberculosis and Mycobacterium smegmatis [J].

Carroll, P ;

Muttucumaru, DGN ;

Parish, T .

APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2005, 71 (06) :3077-3084

[4]

Functional analysis of GlnE, an essential adenylyl transferase in Mycobacterium tuberculosis [J].

Carroll, Paul ;

Pashley, Carey A. ;

Parish, Tanya .

JOURNAL OF BACTERIOLOGY, 2008, 190 (14) :4894-4902

[5]

Goude Renan, 2008, V465, P203, DOI [10.1007/978-1-59745-207-6_13, 10.3791/761]

[6]

All four Mycobacterium tuberculosis glnA genes encode glutamine synthetase activities but only GlnA1 is abundantly expressed and essential for bacterial homeostasis [J].

Harth, G ;

Maslesa-Galic, S ;

Tullius, MV ;

Horwitz, MA .

MOLECULAR MICROBIOLOGY, 2005, 58 (04) :1157-1172

[7]

Prioritizing genomic drug targets in pathogens:: Application to Mycobacterium tuberculosis [J].

Hasan, Samiul ;

Daugelat, Sabine ;

Rao, P. S. Srinivasa ;

Schreiber, Mark .

PLOS COMPUTATIONAL BIOLOGY, 2006, 2 (06) :539-550

[8]

Lukey P T, 2001, Methods Mol Med, V54, P271, DOI 10.1385/1-59259-147-7:271

[9]

Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis [J].

Makarov, Vadim ;

Manina, Giulia ;

Mikusova, Katarina ;

Moellmann, Ute ;

Ryabova, Olga ;

Saint-Joanis, Brigitte ;

Dhar, Neeraj ;

Pasca, Maria Rosalia ;

Buroni, Silvia ;

Lucarelli, Anna Paola ;

Milano, Anna ;

De Rossi, Edda ;

Belanova, Martina ;

Bobovska, Adela ;

Dianiskova, Petronela ;

Kordulakova, Jana ;

Sala, Claudia ;

Fullam, Elizabeth ;

Schneider, Patricia ;

McKinney, John D. ;

Brodin, Priscille ;

Christophe, Thierry ;

Waddell, Simon ;

Butcher, Philip ;

Albrethsen, Jakob ;

Rosenkrands, Ida ;

Brosch, Roland ;

Nandi, Vrinda ;

Bharath, Sowmya ;

Gaonkar, Sheshagiri ;

Shandil, Radha K. ;

Balasubramanian, Venkataraman ;

Balganesh, Tanjore ;

Tyagi, Sandeep ;

Grosset, Jacques ;

Riccardi, Giovanna ;

Cole, Stewart T. .

SCIENCE, 2009, 324 (5928) :801-804

[10]

targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis [J].

Raman, Karthik ;

Yeturu, Kalidas ;

Chandra, Nagasuma .

BMC SYSTEMS BIOLOGY, 2008, 2