Key targets and relevant inhibitors for the drug discovery of tuberculosis

Current Drug Targets

Volumn 14, Issue 6, 2013, Pages 676-699

  Xiong, Xiuming ^a,b   Xu, Zhijian ^b   Yang, Zhuo ^b   Liu, Yingtao ^b   Wang, Di ^c   Dong, Mei ^c   Parker, Emily J ^d   Zhu, Weiliang ^a,b  

^a NANCHANG UNIVERSITY   (China)

^b SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^c 309TH HOSPITAL OF PLA   (China)

^d UNIVERSITY OF CANTERBURY   (New Zealand)

Author keywords

Antimycobacterial; Dormant; Drug resistant; Inhibitors; Mycobacterium tuberculosis; New targets

Indexed keywords

6, 7 DIHYDRO 2 NITRO 6 (4 TRIFLUOROMETHOXYBENZYLOXY) 5H IMIDAZO [2, 1 B] [1, 3] OXAZINE; 6,7 DIHYDRO 2 NITRO 6 (4 TRIFLUOROMETHOXYBENZYLOXY) 5H IMIDAZO[2,1 B][1,3]OXAZINE; ALANINE RACEMASE; AMIKACIN; ANTHRANILATE PHOSPHORIBOSYLTRANSFERASE; ARABINOGALACTAN; AZD 5847; BEDAQUILINE; BIOTIN; CAPREOMYCIN; CIPROFLOXACIN; DELAMANID; DEXTRO ALANINE DEXTRO ALANINE LIGASE; DIHYDRODIPICOLINATE REDUCTASE; ETHAMBUTOL PLUS ISONIAZID PLUS PYRAZINAMIDE PLUS RIFAMPICIN; ETHIONAMIDE; KANAMYCIN; LEVOFLOXACIN; LINEZOLID; MOXIFLOXACIN; MYCOLIC ACID; N (2 ADAMANTYL) N' GERANYLETHYLENEDIAMINE; OFLOXACIN; PEPTIDOGLYCAN; POSIZOLID; PYRAZINAMIDE; RIFABUTIN; RIFAPENTINE; STREPTOMYCIN; SUTEZOLID; THYMIDYLATE SYNTHASE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIBACTERIAL ACTIVITY; BACTERIAL GROWTH; BACTERIAL SURVIVAL; BACTERICIDAL ACTIVITY; BIOSYNTHESIS; CHEMICAL STRUCTURE; ENZYME ACTIVITY; HUMAN; IMMUNE SYSTEM; MINIMUM INHIBITORY CONCENTRATION; MOLECULAR BIOLOGY; MYCOBACTERIUM TUBERCULOSIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PREVALENCE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; TUBERCULOSIS;

ANIMALS; ANTITUBERCULAR AGENTS; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DRUG DELIVERY SYSTEMS; DRUG DISCOVERY; HUMANS; MYCOBACTERIUM TUBERCULOSIS; TUBERCULOSIS;

EID: 84878621441     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/1389450111314060009     Document Type: Review

References (189)

1. Frieden TR, Sterling TR, Munsiff SS, Watt CJ, Dye C. Tuberculosis. Lancet 2003; 362(9387): 887-899.
2. Koul A, Arnoult E, Lounis N, Guillemont J, Andries K. The challenge of new drug discovery for tuberculosis. Nature 2011; 469(7331): 483-490.
3. Murphy DJ, Brown JR. Novel drug target strategies against Mycobacterium tuberculosis. Curr Opin Microbiol 2008; 11(5): 422-427.
4. Kaufmann SH, Hussey GD, Lambert PH. New vaccines for tuberculosis. Lancet 2010; 375: 2110-2119.
5. Brennan PJ, Crick DC. The Cell-Wall Core of Mycobacterium tuberculosis in the Context of Drug Discovery. Curr Top Med Chem 2007; 7: 475-488.
6. Mdluli K, Spigelman M. Novel targets for tuberculosis drug discovery. Curr Opin Pharmacol 2006; 6(5): 459-467.
7. Brennan PJ. Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2003; 83(1-3): 91-97.
8. Goude R, Parish T. The genetics of cell wall biosynthesis in Mycobacterium tuberculosis. Future Microbiol 2008; 3: 299-313.
9. Zoeiby AE, Sanschagrin F, Levesque RC. Structure and function of the Mur enzymes development of novel inhibitors. Mol Microbiol 2003; 47: 1-12.
10. Anthony KG, Strych U, Yeung KR, et al. New Classes of Alanine Racemase Inhibitors Identified by High-Throughput Screening Show Antimicrobial Activity against Mycobacterium tuberculosis. PLoS One 2011; 6: 1-9.
11. Lew JM, Kapopoulou A, Jones LM, Cole ST. TubercuList-10 years after. Tuberculosis (Edinb) 2011; 91(1): 1-7.
12. Bruning JB, Murillo AC, Chacon O, Barletta RG, Sacchettini JC. Structure of the Mycobacterium tuberculosis D-alanine:D-alanine ligase, a target of the antituberculosis drug D-cycloserine. Antimicrob Agents Chemother 2011; 55(1): 291-301.
13. Kefala G, Evans GL, Griffin MD, et al. Crystal structure and kinetic study of dihydrodipicolinate synthase from Mycobacterium tuberculosis. Biochem J 2008; 411(2): 351-360.
14. Cox RJ, Sutherland A, Vederas JC. Bacterial diaminopimelate metabolism as a target for antibiotic design. Bioorg Med Chem 2000; 8: 843-871.
15. Hutton CA, Southwood TJ, Turner JJ. Inhibitors of lysine biosynthesis as antibacterial agents. Mini Rev Med Chem 2003; 3: 115-127.
16. Paiva AM, Vanderwall DE, Blanchard JS, et al. Inhibitors of dihydrodipicolinate reductase, a key enzyme of the diaminopimelate pathway of Mycobacterium tuberculosis. Biochimica et Biophysica Acta 2001; 1545: 67-77.
17. Gupta R, Lavollay M, Mainardi JL, et al. The Mycobacterium tuberculosis protein LdtMt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin. Nat Med 2010; 16(4): 466-469.
18. Dubee V, Triboulet S, Mainardi JL, et al. Inactivation of Mycobacterium tuberculosis l,d-transpeptidase LdtMt(1) by carbapenems and cephalosporins. Antimicrob Agents Chemother 2012; 56(8): 4189-4195.
19. Nikonenko BV, Reddy VM, Protopopova M, et al. Activity of SQ641, a capuramycin analog, in a murine model of tuberculosis. Antimicrob Agents Chemother 2009; 53(7): 3138-3139.
20. Manina G, Pasca MR, Buroni S, Rossi ED, Riccardi G. Decaprenylphosphoryl-[1]-D-Ribose 2'-Epimerase from Mycobacterium tuberculosis is a Magic Drug Target. Curr Med Chem 2010; 17: 3099-3108.
21. Wolucka BA. Biosynthesis of D-arabinose in mycobacteria -a novel bacterial pathway with implications for antimycobacterial therapy. FEBS J 2008; 275(11): 2691-2711.
22. Pasca MR, Degiacomi G, Ribeiro AL, et al. Clinical isolates of Mycobacterium tuberculosis in four European hospitals are uniformly susceptible to benzothiazinones. Antimicrob Agents Chemother 2010; 54(4): 1616-1618.
23. Makarov V, Manina G, Mikusova K, et al. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science 2009; 324(5928): 801-804.
24. (WGNTD) WGoNTD. Drug Pipeline BTZ043 [cited 2012 October 23]; Available from: http://www.newtbdrugs.org/project.php?id=162.
25. Alderwick LJ, Seidel M, Sahm H, Besra GS, Eggeling L. Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J Biol Chem 2006; 281(23): 15653-16661.
26. Seidel M, Alderwick LJ, Birch HL, et al. Identification of a novel arabinofuranosyltransferase AftB involved in a terminal step of cell wall arabinan biosynthesis in Corynebacterianeae, such as Corynebacterium glutamicum and Mycobacterium tuberculosis. J Biol Chem 2007; 282(20): 14729-14740.
27. Li W, Xin Y, McNeil MR, Ma Y. rmlB and rmlC genes are essential for growth of mycobacteria. Biochem Biophys Res Commun 2006; 342(1): 170-178.
28. Sivendran S, Jones V, Sun D, et al. Identification of triazinoindolbenzimidazolones as nanomolar inhibitors of the Mycobacterium tuberculosis enzyme TDP-6-deoxy-d-xylo-4-hexopyranosid-4-ulose 3,5-epimerase (RmlC). Bioorg Med Chem 2010; 18(2): 896-908.
29. Wang Y, Hess TN, Jones V, et al. Novel inhibitors of Mycobacterium tuberculosis dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmlD) identified by virtual screening. Bioorg Med Chem Lett 2011; 21(23): 7064-7067.
30. Huang CC, Smith CV, Glickman MS, Jacobs WR, Jr., Sacchettini JC. Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis. J Biol Chem 2002; 277(13): 11559-11569.
31. Barry CE, Lee RE, Mdluli K, et al. Mycolic acids structure, biosynthesis and physiological functions. Prog Lipid Res 1998; 37: 143-179.
32. Tahlan K, Wilson R, Kastrinsky DB, et al. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2012; 56(4): 1797-1809.
33. Sacksteder KA, Protopopova M, Barry CE, Andries K, Nacy CA. Discovery and development of SQ109 a new antitubercular drug with a novel mechanism of action. Future Microbiol 2012; 7: 823-837.
34. ThomsonReuters. Thomson Pharma Drug Report: SQ109. 2013.
35. Matsumoto M, Hashizume H, Tomishige T, et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med 2006; 3: 2131-2144.
36. ThomsonReuters. Thomson Pharma Drug Report: OPC-67683. 2013.
37. Singh R, Manjunatha U, Boshoff H, et al. PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release. Science 2008; 322: 1392-1395.
38. ThomsonReuters. Thomson Pharma Drug Report: PA-824. 2013.
39. Manjunatha UH, Boshoff H, Dowd CS, et al. Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2006; 103(2): 431-436.
40. Luckner SR, Machutta CA, Tonge PJ, Kisker C. Crystal structures of Mycobacterium tuberculosis KasA show mode of action within cell wall biosynthesis and its inhibition by thiolactomycin. Structure 2009; 17(7): 1004-1013.
41. Sridharan S, Wang L, Brown AK, et al. X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier protein synthase II (mtKasB). J Mol Biol 2007; 366(2): 469-480.
42. Kremer L, Douglas JD, Baulard AR, et al. Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis. J Biol Chem 2000; 275(22): 16857-16864.
43. Musayev F, Sachdeva S, Scarsdale JN, Reynolds KA, Wright HT. Crystal structure of a substrate complex of Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FabH) with lauroyl-coenzyme A. J Mol Biol 2005; 346(5): 1313-1321.
44. Cohen-Gonsaud M, Ducasse S, Hoh F, et al. Crystal Structure of MabA from Mycobacterium tuberculosis, a Reductase involved in Long-chain Fatty Acid Biosynthesis. J Mol Biol 2002; 320(2): 249-261.
45. Marrakchi H, Ducasse S, Labesse G, et al. MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II. Microbiology 2001; 148: 951-960.
46. Vilcheze C, Baughn AD, Tufariello J, et al. Novel inhibitors of InhA efficiently kill Mycobacterium tuberculosis under aerobic and anaerobic conditions. Antimicrob Agents Chemother 2011; 55(8): 3889-3898.
47. Banerjee A, Dubnau E, Quemard A, et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 1994; 263: 227-30.
48. Luckner SR, Liu N, am Ende CW, Tonge PJ, Kisker C. A slow, tight binding inhibitor of InhA, the enoyl-acyl carrier protein reductase from Mycobacterium tuberculosis. J Biol Chem 2010; 285(19): 14330-14337.
49. am Ende CW, Knudson SE, Liu N, et al. Synthesis and in vitro antimycobacterial activity of B-ring modified diaryl ether InhA inhibitors. Bioorg Med Chem Lett 2008; 18(10): 3029-3033.
50. Glickman MS, Cox JS, Jacobs WR. A Novel Mycolic Acid Cyclopropane Synthetase Is Required for Cording, Persistence, and Virulence of Mycobacterium tuberculosis. Mol Cell 2000; 5: 717-727.
51. Yuan Y, Lee RE, Besra GS, Belisle JT, Barry CE. Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 1995; 92(6630-6634).
52. Gavalda S, Leger M, van der Rest B, et al. The Pks13/FadD32 crosstalk for the biosynthesis of mycolic acids in Mycobacterium tuberculosis. J Biol Chem 2009; 284(29): 19255-19264.
53. Leger M, Gavalda S, Guillet V, et al. The dual function of the Mycobacterium tuberculosis FadD32 required for mycolic acid biosynthesis. Chem Biol 2009; 16(5): 510-519.
54. Portevin D, de Sousa-D'Auria C, Montrozier H, et al. The acyl-AMP ligase FadD32 and AccD4-containing acyl-CoA carboxylase are required for the synthesis of mycolic acids and essential for mycobacterial growth: identification of the carboxylation product and determination of the acyl-CoA carboxylase components. J Biol Chem 2005; 280(10): 8862-8874.
55. Khare G, Gupta V, Gupta RK, et al. Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis. PLoS One 2009; 4: 1-15.
56. Goude R, Amin AG, Chatterjee D, Parish T. The critical role of embC in Mycobacterium tuberculosis. J Bacteriol 2008; 190(12): 4335-4341.
57. Amin AG, Goude R, Shi L, et al. EmbA is an essential arabinosyltransferase in Mycobacterium tuberculosis. Microbiology 2008; 154(Pt 1): 240-248.
58. Goude R, Amin AG, Chatterjee D, Parish T. The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2009; 53(10): 4138-4146.
59. Pereira PJ, Empadinhas N, Albuquerque L, et al. Mycobacterium tuberculosis glucosyl-3-phosphoglycerate synthase: structure of a key enzyme in methylglucose lipopolysaccharide biosynthesis. PLoS One 2008; 3(11): e3748.
60. Zhang Z, Bulloch EM, Bunker RD, Baker EN, Squire CJ. Structure and function of GlmU from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr 2009; 65(Pt 3): 275-283.
61. Li Y, Zhou Y, Ma Y, Li X. Design and synthesis of novel cell wall inhibitors of Mycobacterium tuberculosis GlmM and GlmU. Carbohydr Res 2011; 346(13): 1714-1720.
62. Kurabachew M, Lu SH, Krastel P, et al. Lipiarmycin targets RNA polymerase and has good activity against multidrug-resistant strains of Mycobacterium tuberculosis. J Antimicrob Chemother 2008; 62(4): 713-719.
63. Srivastava A, Talaue M, Liu S, et al. New target for inhibition of bacterial RNA polymerase: 'switch region'. Curr Opin Microbiol 2011; 14(5): 532-543.
64. Mdluli K, Ma ZK. Mycobacterium tuberculosis DNA gyrase as a target for drug discovery. Infect Disord Drug Targets 2007; 7: 159-168.
65. Chopra S, Matsuyama K, Tran T, et al. Evaluation of gyrase B as a drug target in Mycobacterium tuberculosis. J Antimicrob Chemother 2012; 67(2): 415-421.
66. Villemagne B, Crauste C, Flipo M, et al. Tuberculosis: the drug development pipeline at a glance. Eur J Med Chem 2012; 51: 1-16.
67. ThomsonReuters. Thomson Pharma Drug Report: Moxifloxacin. 2013.
68. Biswas T, Tsodikov OV. Hexameric ring structure of the Nterminal domain of Mycobacterium tuberculosis DnaB helicase. FEBS J 2008; 275(12): 3064-3071.
69. Stallings CL, Stephanou NC, Chu L, et al. CarD is an essential regulator of rRNA transcription required for Mycobacterium tuberculosis persistence. Cell 2009; 138(1): 146-159.
70. Lamichhane G. Novel targets in M. tuberculosis: search for new drugs. Trends Mol Med 2010; 17(1): 25-33.
71. Dawes SS, Warner DF, Tsenova L, et al. Ribonucleotide Reduction in Mycobacterium tuberculosis: Function and Expression of Genes Encoding Class Ib and Class II Ribonucleotide Reductases. Infect Immun 2003; 71(11): 6124-61.
72. Nurbo J, Roos AK, Muthas D, et al. Design, synthesis and evaluation of peptide inhibitors of Mycobacterium tuberculosis ribonucleotide reductase. J Pept Sci 2007; 13(12): 822-832.
73. Fivian-Hughes AS, Houghton J, Davis EO. Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid. Microbiology 2012; 158(Pt 2): 308-318.
74. Kogler M, Vanderhoydonck B, De Jonghe S, et al. Synthesis and evaluation of 5-substituted 2'-deoxyuridine monophosphate analogues as inhibitors of flavin-dependent thymidylate synthase in Mycobacterium tuberculosis. J Med Chem 2011; 54(13): 4847-4862.
75. Srivastava SK, Tripathi RP, Ramachandran R. NAD+-dependent DNA Ligase (Rv3014c) from Mycobacterium tuberculosis. Crystal structure of the adenylation domain and identification of novel inhibitors. J Biol Chem 2005; 280(34): 30273-30281.
76. Srivastava SK, Dube D, Kukshal V, et al. NAD+-dependent DNA ligase (Rv3014c) from Mycobacterium tuberculosis: novel structure-function relationship and identification of a specific inhibitor. Proteins 2007; 69(1): 97-111.
77. Nilsson MT, Krajewski WW, Yellagunda S, et al. Structural basis for the inhibition of Mycobacterium tuberculosis glutamine synthetase by novel ATP-competitive inhibitors. J Mol Biol 2009; 393(2): 504-513.
78. Harth G, Clemens DL, Horwitz MA. Glutamine synthetase of Mycobacterium tuberculosis extracellular release and characterization of its enzymatic activity. Proc Natl Acad Sci USA 1994; 91: 9342-9346.
79. Cho Y, Ioerger TR, Sacchettini JC. Discovery of Novel Nitrobenzothiazole Inhibitors for Mycobacterium tuberculosis ATP Phosphoribosyl Transferase (HisG) through Virtual Screening. J Med Chem 2008; 51: 5984-5992.
80. Lee CE, Goodfellow C, Javid-Majd F, Baker EN, Shaun Lott J. The crystal structure of TrpD, a metabolic enzyme essential for lung colonization by Mycobacterium tuberculosis, in complex with its substrate phosphoribosylpyrophosphate. J Mol Biol 2006; 355(4): 784-797.
81. Shen H, Wang F, Zhang Y, et al. A novel inhibitor of indole-3-glycerol phosphate synthase with activity against multidrugresistant Mycobacterium tuberculosis. FEBS J 2009; 276(1): 144-154.
82. Castell A, Short FL, Evans GL, et al. The Substrate Capture Mechanism of Mycobacterium tuberculosis Anthranilate Phosphoribosyltransferase Provides a Mode for Inhibition. Biochemistry 2013; 52: 1776-1787.
83. Cole ST, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998; 393: 537-544.
84. Cherney LT, Cherney MM, Garen CR, et al. Crystal structure of Nacetyl-gamma-glutamyl-phosphate reductase from Mycobacterium tuberculosis in complex with NADP(+). J Mol Biol 2007; 367(5): 1357-1369.
85. Le DT, Lee HS, Chung YJ, Yoon MY, Choi JD. Virtual Screening of Tubercular Acetohydroxy Acid Synthase Inhibitors through Analysis of Structural Models. Bull Korean Chem Soc 2007; 28: 947-952.
86. Pan L, Jiang Y, Liu Z, et al. Synthesis and evaluation of novel monosubstituted sulfonylurea derivatives as antituberculosis agents. Eur J Med Chem 2012; 50: 18-26.
87. Wang D, Pan L, Cao G, et al. Evaluation of the in vitro and intracellular efficacy of new monosubstituted sulfonylureas against extensively drug-resistant tuberculosis. Int J Antimicrob Agents 2012; 40(5): 463-466.
88. Karim M, Shim MY, Kim J, et al. The Catalytic Role of the W573 in the Mobile Loop of Recombinant Acetohydroxyacid Synthase from Tobacco. Bull Korean Chem Soc 2006; 27: 549-555.
89. Singh V, Chandra D, Srivastava BS, Srivastava R. Biochemical and transcription analysis of acetohydroxyacid synthase isoforms in Mycobacterium tuberculosis identifies these enzymes as potential targets for drug development. Microbiology 2011; 157(Pt 1): 29-37.
90. Sohn H, Lee KS, Ko YK, et al. In vitro and ex vivo activity of new derivatives of acetohydroxyacid synthase inhibitors against Mycobacterium tuberculosis and non-tuberculous mycobacteria. Int J Antimicrob Agents 2008; 31(6): 567-571.
91. Lu JP, Chai SC, Ye QZ. Catalysis and inhibition of Mycobacterium tuberculosis methionine aminopeptidase. J Med Chem 2010; 53(3): 1329-1337.
92. Olaleye O, Raghunand TR, Bhat S, et al. Methionine aminopeptidases from Mycobacterium tuberculosis as novel antimycobacterial targets. Chem Biol 2010; 17(1): 86-97.
93. Lu JP, Yuan XH, Ye QZ. Structural analysis of inhibition of Mycobacterium tuberculosis methionine aminopeptidase by bengamide derivatives. Eur J Med Chem 2012; 47(1): 479-484.
94. Agrawal H, Kumar A, Bal NC, Siddiqi MI, Arora A. Ligand based virtual screening and biological evaluation of inhibitors of chorismate mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv. Bioorg Med Chem Lett 2007; 17(11): 3053-3058.
95. Munack S, Leroux V, Roderer K, Krengel U. When Inhibitors Do Not Inhibit: Critical Evaluation of Rational Drug Design Targeting Chorismate Mutase from Mycobacterium tuberculosis. Chem Biodivers 2012; 9(11): 2507-2527.
96. Sasso S, Okvist M, Roderer K, et al. Structure and function of a complex between chorismate mutase and DAHP synthase: efficiency boost for the junior partner. EMBO J 2009; 28(14): 2128-2142.
97. Kim SK, Reddy SK, Nelson BC, et al. A comparative biochemical and structural analysis of the intracellular chorismate mutase (Rv0948c) from Mycobacterium tuberculosis H(37)R(v) and the secreted chorismate mutase (y2828) from Yersinia pestis. FEBS J 2008; 275(19): 4824-4835.
98. Pichota A, Duraiswamy J, Yin Z, et al. Peptide deformylase inhibitors of Mycobacterium tuberculosis: synthesis, structural investigations, and biological results. Bioorg Med Chem Lett 2008; 18(24): 6568-6572.
99. Teo JW, Thayalan P, Beer D, et al. Peptide deformylase inhibitors as potent antimycobacterial agents. Antimicrob Agents Chemother 2006; 50(11): 3665-3673.
100. Alffenaar JW, van der Laan T, Simons S, et al. Susceptibility of clinical Mycobacterium tuberculosis isolates to a potentially less toxic derivate of linezolid, PNU-100480. Antimicrob Agents Chemother 2011; 55(3): 1287-1289.
101. ThomsonReuters. Thomson Pharma Drug Report: PNU-100480. 2013.
102. ThomsonReuters. Thomson Pharma Drug Report: AZD-5847. 2013.
103. Alangaden GJ, Kreiswirth BN, Aouad A, et al. Mechanism of Resistance to Amikacin and Kanamycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998; 42: 1295-1297.
104. Shi W, Zhang X, Jiang X, et al. Pyrazinamide inhibits transtranslation in Mycobacterium tuberculosis. Science 2011; 333(6049): 1630-1632.
105. Mann S, Ploux O. 7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a potential therapeutic target. Characterization and inhibition studies. FEBS J 2006; 273(20): 4778-4789.
106. Mann S, Colliandre L, Labesse G, Ploux O. Inhibition of 7,8-diaminopelargonic acid aminotransferase from Mycobacterium tuberculosis by chiral and achiral anologs of its substrate: biological implications. Biochimie 2009; 91(7): 826-834.
107. Keer J, Smeulders MJ, Gray KL, Williams HD. Mutants of Mycobacterium smegmatis impaired in stationary-phase survival. Microbiology 2000; 146: 2209-2217.
108. White EL, Southworth K, Ross L, et al. A novel inhibitor of Mycobacterium tuberculosis pantothenate synthetase. J Biomol Screen 2007; 12(1): 100-105.
109. Sledz P, Silvestre HL, Hung AW, et al. Optimization of the Interligand Overhauser Effect for Fragment Linking Application to Inhibitor Discovery against Mycobacterium tuberculosisPantothenate Synthetase. J Am Chem Soc 2010; (132): 4544-4545.
110. Ciulli A, Scott DE, Ando M, et al. Inhibition of Mycobacterium tuberculosis pantothenate synthetase by analogues of the reaction intermediate. Chembiochem 2008; 9(16): 2606-2611.
111. Hung AW, Silvestre HL, Wen S, et al. Application of fragment growing and fragment linking to the discovery of inhibitors of Mycobacterium tuberculosis pantothenate synthetase. Angew Chem Int Ed Engl 2009; 48(45): 8452-8456.
112. Velaparthi S, Brunsteiner M, Uddin R, Uddin B. 5-tert-Butyl-Npyrazol-4-yl-4,5,6,7-tetrahydrobenzo [d]isoxazole-3-carboxamide Derivatives as Novel Potent Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Initiating a Quest for New Antitubercular Drugs. J Med Chem 2008; 51: 1999-2002.
113. Awasthy D, Ambady A, Bhat J, et al. Essentiality and functional analysis of type I and type III pantothenate kinases of Mycobacterium tuberculosis. Microbiology 2010; 156(Pt 9): 2691-2701.
114. Venkatraman J, Bhat J, Solapure SM, et al. Screening, identification, and characterization of mechanistically diverse inhibitors of the Mycobacterium tuberculosis enzyme, pantothenate kinase (CoaA). J Biomol Screen 2012; 17(3): 293-302.
115. Li R, Sirawaraporn R, Chitnumsub P, et al. Three-dimensional structure of M-tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. J Mol Biol 2000; 295: 307-323.
116. El-Hamamsy MH, Smith AW, Thompson AS, Threadgill MD. Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis. Bioorg Med Chem 2007; 15(13): 4552-4576.
117. Goulding CW, Apostol MI, Sawaya MR, et al. Regulation by oligomerization in a mycobacterial folate biosynthetic enzyme. J Mol Biol 2005; 349(1): 61-72.
118. Morgunova E, Meining W, Illarionov B, et al. Crystal Structure of Lumazine Synthase from Mycobacterium tuberculosis as a Target for Rational Drug Design Binding Mode of a New Class of Purinetrione. Biochemistry 2005; 44: 2746-2758.
119. Morgunova E, Illarionov B, Sambaiah T, et al. Structural and thermodynamic insights into the binding mode of five novel inhibitors of lumazine synthase from Mycobacterium tuberculosis. FEBS J 2006; 273(20): 4790-4804.
120. Dhiman RK, Mahapatra S, Slayden RA, et al. Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non-replicating persistence. Mol Microbiol 2009; 72(1): 85-97.
121. Truglio JJ, Theis K, Feng Y, et al. Crystal structure of Mycobacterium tuberculosis MenB, a key enzyme in vitamin K2 biosynthesis. J Biol Chem 2003; 278(43): 42352-42360.
122. Li X, Liu N, Zhang H, et al. Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis. Bioorg Med Chem Lett 2010; 20(21): 6306-6309.
123. Belin P, Le Du MH, Fielding A, et al. Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 2009; 106(18): 7426-7431.
124. McLean KJ, Dunford AJ, Neeli R, Driscoll MD, Munro AW. Structure, function and drug targeting in Mycobacterium tuberculosis cytochrome P450 systems. Arch Biochem Biophys 2007; 464(2): 228-240.
125. Ouellet H, Johnston JB, Ortiz de Montellano PR. The Mycobacterium tuberculosis cytochrome P450 system. Arch Biochem Biophys 2010; 493(1): 82-95.
126. Hudson SA, McLean KJ, Surade S, et al. Application of Fragment Screening and Merging to the Discovery of Inhibitors of the Mycobacterium tuberculosis Cytochrome P450 CYP121. Angew Chem Int Ed Engl 2012; (51): 9311-9316.
127. Eoh H, Brennan PJ, Crick DC. The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target. Tuberculosis (Edinb) 2009; 89(1): 1-11.
128. Henriksson LM, Unge T, Carlsson J, et al. Structures of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase provide new insights into catalysis. J Biol Chem 2007; 282(27): 19905-19916.
129. Mao J, Eoh H, He R, et al. Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-Dxylulose 5-phosphate synthase. Bioorg Med Chem Lett 2008; 18(19): 5320-5323.
130. Shi W, Feng J, Zhang M, et al. Biosynthesis of Isoprenoids Characterization of a Functionally Active Recombinant 2-Cmethyl-D-erythritol 4-phosphate Cytidyltransferase (IspD) from Mycobacterium tuberculosis H37Rv. J Biochem Mol Biol 2007; 40: 911-920.
131. Narayanasamy P, Eoh H, Brennan PJ, Crick DC. Synthesis of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate and kinetic studies of Mycobacterium tuberculosis IspF. Chem Biol 2010; 17(2): 117-122.
132. Geist JG, Lauw S, Illarionova V, et al. Thiazolopyrimidine inhibitors of 2-methylerythritol 2,4-cyclodiphosphate synthase (IspF) from Mycobacterium tuberculosis and Plasmodium falciparum. ChemMedChem 2010; 5(7): 1092-1101.
133. Kapnick SM, Zhang Y. New tuberculosis drug development targeting the shikimate pathway. Expert Opin Drug Discov 2008; 3: 565-577.
134. Webby CJ, Baker HM, Lott JS, Baker EN, Parker EJ. The structure of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis reveals a common catalytic scaffold and ancestry for type I and type II enzymes. J Mol Biol 2005; 354(4): 927-939.
135. Reichau S, Jiao W, Walker SR, et al. Potent inhibitors of a shikimate pathway enzyme from Mycobacterium tuberculosis: combining mechanism-and modeling-based design. J Biol Chem 2011; 286(18): 16197-16207.
136. Webby CJ, Jiao W, Hutton RD, et al. Synergistic allostery, a sophisticated regulatory network for the control of aromatic amino acid biosynthesis in Mycobacterium tuberculosis. J Biol Chem 2010; 285(40): 30567-30576.
137. Jiao W, Hutton RD, Cross PJ, Jameson GB, Parker EJ. Dynamic cross-talk among remote binding sites: the molecular basis for unusual synergistic allostery. J Mol Biol 2012; 415(4): 716-726.
138. Sanchez-Sixto C, Prazeres VF, Castedo L, et al. Structure-Based Design, Synthesis, and Biological Evaluation of Inhibitors of Mycobacterium tuberculosis Type II Dehydroquinase. J Med Chem 2005; 48: 4871-4881.
139. Dias MV, Snee WC, Bromfield KM, et al. Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis. Biochem J 2011; 436(3): 729-739.
140. Tran AT, West NP, Britton WJ, Payne RJ. Elucidation of Mycobacterium tuberculosis type II dehydroquinase inhibitors using a fragment elaboration strategy. ChemMedChem 2012; 7(6): 1031-1043.
141. Prazeres VF, Sanchez-Sixto C, Castedo L, et al. Nanomolar competitive inhibitors of Mycobacterium tuberculosis and Streptomyces coelicolor type II dehydroquinase. ChemMedChem 2007; 2(2): 194-207.
142. Arcuri HA, Borges JC, Fonseca IO, et al. Structural studies of shikimate 5-dehydrogenase from Mycobacterium tuberculosis. Proteins 2008; 72(2): 720-730.
143. Rodrigues VS, Jr., Breda A, Santos DS, Basso LA. The conserved Lysine69 residue plays a catalytic role in Mycobacterium tuberculosis shikimate dehydrogenase. BMC Res Notes 2009; 2: 227.
144. Segura-Cabrera A, Rodriguez-Perez MA. Structure-based prediction of Mycobacterium tuberculosis shikimate kinase inhibitors by high-throughput virtual screening. Bioorg Med Chem Lett 2008; 18(11): 3152-3157.
145. Dias MV, Borges JC, Ely F, et al. Structure of chorismate synthase from Mycobacterium tuberculosis. J Struct Biol 2006; 154(2): 130-143.
146. Kitzing K, Auweter S, Amrhein N, Macheroux P. Mechanism of chorismate synthase. Role of the two invariant histidine residues in the active site. J Biol Chem 2004; 279(10): 9451-9461.
147. Arcuri HA, Palma MS. Understanding the Structure, Activity and Inhibition of Chorismate Synthase from Mycobacterium tuberculosis. Curr Med Chem 2011; 18: 1311-1317.
148. Hurdle JG, O'Neill AJ, Chopra I, Lee RE. Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nat Rev Microbiol 2011; 9(1): 62-75.
149. Koul A, Dendouga N, Vergauwen K, et al. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat Chem Biol 2007; 3: 323-324.
150. Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005; 307(5707): 223-227.
151. ThomsonReuters. Thomson Pharma Drug Report: TMC-207. 2013.
152. Zhou B, He Y, Zhang X, et al. Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents. Proc Natl Acad Sci U S A 2010; 107(10): 4573-4578.
153. Dasgupta N, Kapur V, Singh KK, et al. Characterization of a twocomponent system, devR-devS, of Mycobacterium tuberculosis. Tuber Lung Dis 2000; 80(3): 141-159.
154. Park HD, Guinn KM, Harrell MI, et al. Rv3133c dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol Microbiol 2003; 48: 833-843.
155. Gupta RK, Thakur TS, Desiraju GR, Tyagi JS. Structure-based design of DevR inhibitor active against nonreplicating Mycobacterium tuberculosis. J Med Chem 2009; 52(20): 6324-6334.
156. Szekely R, Waczek F, Szabadkai I, et al. A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling. Immunol Lett 2008; 116(2): 225-231.
157. Scherr N, Honnappa S, Kunz G, et al. Structural basis for the specific inhibition of protein kinase G, a virulence factor of Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2007; 104(29): 12151-12156.
158. Walburger A, Koul A, Ferrari G, et al. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science 2004; 304(5678): 1800-1804.
159. Buchmeier N, Fahey RC. The mshA gene encoding the glycosyltransferase of mycothiol biosynthesis is essential in Mycobacterium tuberculosis Erdman. FEMS Microbiol Lett 2006; 264(1): 74-79.
160. Gutierrez-Lugo MT, Baker H, Shiloach J, Boshoff H, Bewley CA. Dequalinium, a new inhibitor of Mycobacterium tuberculosis mycothiol ligase identified by high-throughput screening. J Biomol Screen 2009; 14(6): 643-652.
161. Newton GL, Buchmeier N, La Clair JJ, Fahey RC. Evaluation of NTF1836 as an inhibitor of the mycothiol biosynthetic enzyme MshC in growing and non-replicating Mycobacterium tuberculosis. Bioorg Med Chem 2011; 19(13): 3956-3964.
162. Ratledge C. Iron, mycobacteria and tuberculosis. Tuberculosis (Edinb) 2004; 84(1-2): 110-130.
163. Harrison AJ, Yu M, Gardenborg T, et al. The structure of MbtI from Mycobacterium tuberculosis, the first enzyme in the biosynthesis of the siderophore mycobactin, reveals it to be a salicylate synthase. J Bacteriol 2006; 188(17): 6081-91.
164. Manos-Turvey A, Bulloch EM, Rutledge PJ, et al. Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI). ChemMedChem 2010; 5(7): 1067-79.
165. Manos-Turvey A, Cergol KM, Salam NK, et al. Synthesis and evaluation of M. tuberculosis salicylate synthase (MbtI) inhibitors designed to probe plasticity in the active site. Org Biomol Chem 2012; 10(46): 9223-9236.
166. Chi G, Manos-Turvey A, O'Connor PD, et al. Implications of binding mode and active site flexibility for inhibitor potency against the salicylate synthase from Mycobacterium tuberculosis. Biochemistry 2012; 51(24): 4868-4879.
167. Vasan M, Neres J, Williams J, et al. Inhibitors of the salicylate synthase (MbtI) from Mycobacterium tuberculosis discovered by high-throughput screening. ChemMedChem 2010; 5(12): 2079-2087.
168. Wang F, Cassidy C, Sacchettini JC. Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics. Antimicrob Agents Chemother 2006; 50(8): 2762-2771.
169. Xu H, Hazra S, Blanchard JS. NXL104 Irreversibly Inhibits the beta-Lactamase from Mycobacterium tuberculosis. Biochemistry 2012; 51(22): 4551-4557.
170. Cosconati S, Hong JA, Novellino E, et al. Structure-based virtual screening and biological evaluation of Mycobacterium tuberculosis adenosine 5'-phosphosulfate reductase inhibitors. J Med Chem 2008; 51(21): 6627-6630.
171. Carta F, Maresca A, Covarrubias AS, et al. Carbonic anhydrase inhibitors. Characterization and inhibition studies of the most active beta-carbonic anhydrase from Mycobacterium tuberculosis, Rv3588c. Bioorg Med Chem Lett 2009; 19(23): 6649-6654.
172. Kalscheuer R, Syson K, Veeraraghavan U, et al. Self-poisoning of Mycobacterium tuberculosis by targeting GlgE in an alpha-glucan pathway. Nat Chem Biol 2010; 6: 376-384.
173. McKinney JD, Miczak A, Chen B, et al. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 2000; 406: 735-738.
174. Sharma V, Sharma S, McKinney JD, et al. Structure of isocitrate lyase,a persistence factor of Mycobacterium tuberculosis. Nat Struct Biol 2000; 7: 663-668.
175. Sriram D, Yogeeswari P, Methuku S, et al. Synthesis of various 3-nitropropionamides as Mycobacterium tuberculosis isocitrate lyase inhibitor. Bioorg Med Chem Lett 2011; 21(18): 5149-5154.
176. Hillas PJ, del Alba FS, Oyarzabal J, Wilks A, Ortiz De Montellano PR. The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis. J Biol Chem 2000; 275(25): 18801-18809.
177. Nunn CM, Djordjevic S, Hillas PJ, Nishida CR, Ortiz de Montellano PR. The crystal structure of Mycobacterium tuberculosis alkylhydroperoxidase AhpD, a potential target for antitubercular drug design. J Biol Chem 2002; 277(22): 20033-200340.
178. Guimaraes BG, Souchon H, Honore N, et al. Structure and mechanism of the alkyl hydroperoxidase AhpC, a key element of the Mycobacterium tuberculosis defense system against oxidative stress. J Biol Chem 2005; 280(27): 25735-25742.
179. Ollinger J, O'Malley T, Kesicki EA, Odingo J, Parish T. Validation of the essential ClpP protease in Mycobacterium tuberculosis as a novel drug target. J Bacteriol 2012; 194(3): 663-668.
180. Kumar K, Awasthi D, Berger WT, Tonge PJ, Slayden RA. Discovery of anti-TB agents that target the cell-division protein FtsZ. Future Med Chem 2010; 2: 1305-1323.
181. Dahl JL, Kraus CN, Boshoff HI, et al. The role of RelMtbmediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc Natl Acad Sci USA 2003; 100(17): 10026-10031.
182. Zumla A, Maeurer M. Rational development of adjunct immunebased therapies for drug-resistant tuberculosis: hypotheses and experimental designs. J Infect Dis 2012; 205 Suppl 2: S335-S339.
183. Cooper AM. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 2009; 27: 393-422.
184. Billeskov R, Elvang TT, Andersen PL, Dietrich J. The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity. PLoS One 2012; 7(6): e39909.
185. Scriba TJ, Tameris M, Smit E, et al. A phase IIa trial of the new tuberculosis vaccine, MVA85A, in HIV-and/or Mycobacterium tuberculosis-infected adults. Am J Respir Crit Care Med 2012; 185(7): 769-778.
186. Ioerger TR, Sacchettini JC. Structural genomics approach to drug discovery for Mycobacterium tuberculosis. Curr Opin Microbiol 2009; 12(3): 318-325.
187. Aldridge BB, Fernandez-Suarez M, Heller D, et al. Asymmetry and Aging of Mycobacterial Cells Lead to Variable Growth and Antibiotic Susceptibility. Sciencexpress 2011; 10: 1-6.
188. Russell DG, Barry CE, 3rd, Flynn JL. Tuberculosis: what we don't know can, and does, hurt us. Science 2010; 328(5980): 852-856.
189. Diacon AH, Dawson R, Groote-Bidlingmaier F, et al. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet 2012; 1-8.