Navigating tuberculosis drug discovery with target-based screening

Expert Opinion on Drug Discovery

Volumn 6, Issue 8, 2011, Pages 839-854

  Miller, Christopher H ^a   O'Toole, Ronan F ^a  

^a VICTORIA UNIVERSITY OF WELLINGTON   (New Zealand)

Author keywords

Drug discovery; Mycobacterium; Targeted screening; Tuberculosis

Indexed keywords

6,7 DIHYDRO 2 NITRO 6 (4 TRIFLUOROMETHOXYBENZYLOXY) 5H IMIDAZO[2,1 B][1,3]OXAZINE; AZD5847; BEDAQUILINE; CAPURAMYCIN; CLOFAZIMINE; DELAMANID; DINITROBENZAMIDE; ETHIONAMIDE; FOLATE BIOSYNTHESIS INHIBITOR; GATIFLOXACIN; GYRASE INHIBITOR; INHA INHIBITOR; ISONIAZID; LINEZOLID; MALATE SYNTHASE INHIBITOR; MENA INHIBITOR; MOXIFLOXACIN; N (2 ADAMANTYL) N' GERANYLETHYLENEDIAMINE; OXABOROLE; PENICILLIN G; PNU 100480; PROTEIN KINASE INHIBITOR; PYRAZINAMIDE; RIFAPENTINE; RUTHENIUM COMPLEX; STREPTOMYCIN; THIOACETAZONE; TRANSLOCASE INHIBITOR; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC SENSITIVITY; B LYMPHOCYTE; COMPUTER MODEL; DRUG CYTOTOXICITY; DRUG MECHANISM; DRUG SCREENING; DRUG TARGETING; GENE EXPRESSION; HUMAN; IN VITRO STUDY; MACROPHAGE; MYCOBACTERIUM MARINUM; MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; STAPHYLOCOCCUS AUREUS; T LYMPHOCYTE; TUBERCULOSIS; WHOLE CELL; ZEBRA FISH;

EID: 79960480130     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2011.586999     Document Type: Review

References (157)

1. World Health Organisation. WHO Report 2010, Global Tuberculosis Control. 2010
2. Wade MM, Zhang Y. Mechanisms of drug resistance in Mycobacterium tuberculosis. Front Biosci 2004;9:975-94 (Pubitemid 39043767)
3. WHO. World Health Organisation and the Stop TB Partnership. Global Plan to Stop TB. 2006
4. Dye C, Espinal MA, Watt CJ, et al. Worldwide incidence of multidrug-resistant tuberculosis. J Infect Dis 2002;185(8):1197-202 (Pubitemid 34297782)
5. WHO. World Health Organisation and the Stop TB Partnership. Building on and enhancing DOTS to meet the TB-related Millennium Development Goals. 2006
6. WHO. World Health Organisation Report 2009, Global Tuberculosis Control: Epidemiology; Strategy; Financing. 2009
7. IUATLD. International Union Against Tuberculosis and Lung Disease, Anti-tuberculosis drug resistance in the world, report no. 4. 2008
8. Dye C, Scheele S, Dolin P, et al. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999;282(7):677-86
9. Gillespie SH. Evolution of drug resistance in Mycobacterium tuberculosis: clinical and molecular perspective. Antimicrob Agents Chemother 2002;46(2):267-74 (Pubitemid 34087167)
10. Gomez JE, McKinney JD. M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis (Edinb) 2004;84(1-2):29-44 (Pubitemid 38082931)
11. Brooker SG, Cambie RC, Cooper RC. New Zealand medicinal plants. 2nd edition. Reed Publishing (NZ) Ltd; Auckland: 1987
12. Earl EA, Altaf M, Murikoli RV, et al. Native New Zealand plants with inhibitory activity towards Mycobacterium tuberculosis. BMC Complement Altern Med 2010;10:25
13. Fleming AB. Penicillin; 1945
14. Waksman SA, Schatz A, Reynolds DM. Production of antibiotic substances by actinomycetes. Ann NY Acad Sci 1946;1213:112-24
15. Waksman SA. Streptomycin: background, isolation, properties, and utilisation. Nobel Lecture, 11 December 1952
16. Fleming AB. The antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B influenzae. Br J Exp Pathol 1929;10:226-36
17. Chain E, Florey HW, Gardner AD, et al. Penicillin as a chemotherapeutic agent. Lancet 1940;II:226-8
18. Chain EB. The chemical structure of the penicillins. Nobel Lecture, March 20, 1946
19. Schatz A, Waksman SA. Effect of streptomycin and other antibiotic substances upon Mycobacterium tuberculosis and related organisms. Proc Soc Exp Biol Med 1944;57:244-8
20. Hinshaw HC, Feldman WH, Pfuetze KH. Streptomycin in treatment of clinical tuberculosis. Am Rev Tuberc 1946;54:191-203
21. Collins LA, Torrero MN, Franzblau SG. Green fluorescent protein reporter microplate assay for high-throughput screening of compounds against Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998;42(2):344-7 (Pubitemid 28114442)
22. Changsen C, Franzblau SG, Palittapongarnpim P. Improved green fluorescent protein reporter gene-based microplate screening for antituberculosis compounds by utilizing an acetamidase promoter. Antimicrob Agents Chemother 2003;47(12):3682-7 (Pubitemid 37484971)
23. Miller CH, Nisa S, Dempsey S, et al. Modifying culture conditions in chemical library screening identifies alternative inhibitors of mycobacteria. Antimicrob Agents Chemother 2009;53(12):5279-83
24. Andrew PW, Roberts IS. Construction of a bioluminescent mycobacterium and its use for assay of antimycobacterial agents. J Clin Microbiol 1993;31(9):2251-4 (Pubitemid 23254183)
25. Cho SH, Warit S, Wan B, et al. Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother 2007;51(4):1380-5 (Pubitemid 46586820)
26. Chung GA, Aktar Z, Jackson S, et al. High-throughput screen for detecting antimycobacterial agents. Antimicrob Agents Chemother 1995;39(10):2235-8
27. Taneja NK, Tyagi JS. Resazurin reduction assays for screening of anti-tubercular compounds against dormant and actively growing Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis. J Antimicrob Chemother 2007;60(2):288-93 (Pubitemid 47243876)
28. Sala C, Dhar N, Hartkoorn RC, et al. Simple model for testing drugs against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother 2010;54(10):4150-8
29. Stover CK, Warrener P, VanDevanter DR, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 2000;405(6789):962-6 (Pubitemid 30435054)
30. Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005;307(5707):223-7 (Pubitemid 40116230)
31. Koul A, Vranckx L, Dendouga N, et al. Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis. J Biol Chem 2008;283(37):25273-80
32. Dhillon J, Andries K, Phillips PP, et al. Bactericidal activity of the diarylquinoline TMC207 against Mycobacterium tuberculosis outside and within cells. Tuberculosis (Edinb) 2010;90(5):301-5
33. Lounis N, Gevers T, Van Den Berg J, et al. ATP Synthase Inhibition of Mycobacterium avium Is Not Bactericidal. Antimicrob Agents Chemother 2009;53(11):4927-9
34. Wayne LG. Dormancy of Mycobacterium tuberculosis and latency of disease. Eur J Clin Microbiol Infect Dis 1994;13(11):908-14
35. Wayne LG, Hayes LG. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun 1996;64(6):2062-9 (Pubitemid 26165667)
36. Wayne LG, Sohaskey CD. Nonreplicating persistence of mycobacterium tuberculosis. Annu Rev Microbiol 2001;55:139-63 (Pubitemid 32978103)
37. Tsai MC, Chakravarty S, Zhu G, et al. Characterization of the tuberculous granuloma in murine and human lungs: cellular composition and relative tissue oxygen tension. Cell Microbiol 2006;8(2):218-32 (Pubitemid 43356045)
38. Via LE, Lin PL, Ray SM, et al. Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect Immun 2008;76(6):2333-40
39. Kharatmal S, Jhamb SS, Singh PP. Evaluation of BACTEC 460 TB system for rapid in vitro screening of drugs against latent state Mycobacterium tuberculosis H37Rv under hypoxia conditions. J Microbiol Methods 2009;78(2):161-4
40. Betts JC, Lukey PT, Robb LC, et al. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 2002;43(3):717-31 (Pubitemid 34597265)
41. Gordhan BG, Smith DA, Alderton H, et al. Construction and phenotypic characterization of an auxotrophic mutant of Mycobacterium tuberculosis defective in L-arginine biosynthesis. Infect Immun 2002;70(6):3080-4 (Pubitemid 34564170)
42. Hampshire T, Soneji S, Bacon J, et al. Stationary phase gene expression of Mycobacterium tuberculosis following a progressive nutrient depletion: a model for persistent organisms? Tuberculosis (Edinb) 2004;84(3-4):228-38 (Pubitemid 38857855)
43. Hondalus MK, Bardarov S, Russell R, et al. Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis. Infect Immun 2000;68(5):2888-98 (Pubitemid 30253869)
44. Smeulders MJ, Keer J, Speight RA, et al. Adaptation of Mycobacterium smegmatis to stationary phase. J Bacteriol 1999;181(1):270-83 (Pubitemid 29013681)
45. Deb C, Lee CM, Dubey VS, et al. A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen. PLoS One 2009;4(6):e6077
46. Projan SJ. New (and not so new) antibacterial targets - from where and when will the novel drugs come? Curr Opin Pharmacol 2002;2(5):513-22
47. Murat AM, Stinebring WR, Schaffner CP, et al. Screening for antibiotics active against intracellular bacteria. Appl Microbiol 1959;7(2):109-12
48. Christophe T, Jackson M, Jeon HK, et al. High content screening identifies decaprenyl-phosphoribose 2 epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog 2009;5(10):e1000645
49. Rosamond J, Allsop A. Harnessing the power of the genome in the search for new antibiotics. Science 2000;287(5460):1973-6 (Pubitemid 30158665)
50. Pucci MJ. Novel genetic techniques and approaches in the microbial genomics era: identification and/or validation of targets for the discovery of new antibacterial agents. Drugs R D 2007;8(4):201-12 (Pubitemid 47026338)
51. Argyrou A, Jin L, Siconilfi-Baez L, et al. Proteome-wide profiling of isoniazid targets in Mycobacterium tuberculosis. Biochemistry 2006;45(47):13947-53 (Pubitemid 44846183)
52. Hughes MA, Silva JC, Geromanos SJ, et al. Quantitative proteomic analysis of drug-induced changes in mycobacteria. J Proteome Res 2006;5(1):54-63 (Pubitemid 43100797)
53. Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005;307(5707):223-7 (Pubitemid 40116230)
54. Koul A, Dendouga N, Vergauwen K, et al. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat Chem Biol 2007;3(6):323-4 (Pubitemid 46789271)
55. Koonin EV. Comparative genomics, minimal gene-sets and the last universal common ancestor. Nat Rev Microbiol 2003;1(2):127-36
56. Mills SD. The role of genomics in antimicrobial discovery. J Antimicrob Chemother 2003;51(4):749-52 (Pubitemid 36503407)
57. Monaghan RL, Barrett JF. Antibacterial drug discovery-Then, now and the genomics future. Biochem Pharmacol 2006;71(7):901-9
58. Lerner CG, Hajduk PJ, Wagner R, et al. From bacterial genomes to novel antibacterial agents: discovery, characterization, and antibacterial activity of compounds that bind to HI0065 (YjeE) from haemophilus influenzae. Chem Biol Drug Des 2007;69(6):395-404 (Pubitemid 46955535)
59. Jordan IK, Rogozin IB, Wolf YI, et al. Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res 2002;12(6):962-8 (Pubitemid 34662289)
60. Fleischmann RD, Adams MD, White O, et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 1995;269(5223):496-512
61. Fraser CM, Gocayne JD, White O, et al. The minimal gene complement of Mycoplasma genitalium. Science 1995;270(5235):397-403
62. Mushegian AR, Koonin EV. A minimal gene set for cellular life derived by comparison of complete bacterial genomes. Proc Natl Acad Sci U S A 1996;93(19):10268-73 (Pubitemid 26314611)
63. Koonin EV. How many genes can make a cell: the minimal-gene-set concept. Annu Rev Genomics Hum Genet 2000;1:99-116
64. Liberati NT, Urbach JM, Miyata S, et al. An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc Natl Acad Sci U S A 2006;103(8):2833-8
65. Liberati NT, Urbach JM, Thurber TK, et al. Comparing insertion libraries in two Pseudomonas aeruginosa strains to assess gene essentiality. Methods Mol Biol 2008;416:153-69 (Pubitemid 351365983)
66. Forsyth RA, Haselbeck RJ, Ohlsen KL, et al. A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol 2002;43(6):1387-400 (Pubitemid 34595533)
67. Thanassi JA, Hartman-Neumann SL, Dougherty TJ, et al. Identification of 113 conserved essential genes using a high-throughput gene disruption system in Streptococcus pneumoniae. Nucleic Acids Res 2002;30(14):3152-62 (Pubitemid 34846179)
68. Song JH, Ko KS, Lee JY, et al. Identification of essential genes in Streptococcus pneumoniae by allelic replacement mutagenesis. Mol Cells 2005;19(3):365-74
69. Sassetti CM, Boyd DH, Rubin EJ. Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 2003;48(1):77-84 (Pubitemid 36411469)
70. Lamichhane G, Zignol M, Blades NJ, et al. A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: application to Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 2003;100(12):7213-18 (Pubitemid 36706418)
71. White TA, Kell DB. Comparative genomic assessment of novel broad-spectrum targets for antibacterial drugs. Comp Funct Genomics 2004;5(4):304-27 (Pubitemid 38807672)
72. Hasan S, Daugelat S, Rao PS, et al. Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis. PLoS Comput Biol 2006;2(6):e61
73. Available from http://www.tdrtargets. org/.The TDR Targets Database v4 - A chemogenomics resource for neglected tropical diseases 2011
74. Crowther GJ, Shanmugam D, Carmona SJ, et al. Identification of attractive drug targets in neglected-disease pathogens using an in silico approach. PLoS Negl Trop Dis 2010;4(8):e804
75. Chen X-P, Du G-H. Target validation: a door to drug discovery. Drug Discov Ther 2007;1(1):23-9
76. Lin T-W, Melgar MM, Kurth D, et al. Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2006;103(9):3072-7 (Pubitemid 43346426)
77. Kurth DG, Gago GM, de la Iglesia A, et al. Accase 6 is the essential acetyl-CoA carboxylase involved in fatty acid and mycolic acid biosynthesis in mycobacteria. Microbiology 2009;155:2664-75
78. Li W, Xin Y, McNeil MR, et al. rmlB and rmlC genes are essential for growth of mycobacteria. Biochem Biophys Res Commun 2006;342(1):170-8 (Pubitemid 43247373)
79. Andres CJ, Bronson JJ, DAndrea SV, et al. 4-Thiazolidinones: novel inhibitors of the bacterial enzyme murB. Bioorg Med Chem Lett 2000;10(8):715-17 (Pubitemid 30215869)
80. Kantardjieff KA, Kim CY, Naranjo C, et al. Mycobacterium tuberculosis RmlC epimerase (Rv3465): a promising drug-target structure in the rhamnose pathway. Acta Crystallogr D Biol Crystallogr 2004;60(Pt 5):895-902 (Pubitemid 41184785)
81. Babaoglu K, Page MA, Jones VC, et al. Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis. Bioorg Med Chem Lett 2003;13(19):3227-30 (Pubitemid 37093833)
82. Dasgupta N, Kapur V, Singh KK, et al. Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis. Tuber Lung Dis 2000;80(3):141-59
83. Sherman DR, Voskuil M, Schnappinger D, et al. Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha -crystallin. Proc Natl Acad Sci USA 2001;98(13):7534-9 (Pubitemid 32567983)
84. OToole R, Smeulders MJ, Blokpoel MC, et al. A two-component regulator of universal stress protein expression and adaptation to oxygen starvation in Mycobacterium smegmatis. J Bacteriol 2003;185(5):1543-54 (Pubitemid 36245956)
85. 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(3):833-43 (Pubitemid 36819066)
86. Gupta RK, Thakur TS, Desiraju GR, et al. Structure-based design of DevR inhibitor active against nonreplicating Mycobacterium tuberculosis. J Med Chem 2009;52(20):6324-34
87. Song CM, Bernardo PH, Chai CL, et al. CLEVER: pipeline for designing in silico chemical libraries. J Mol Graph Model 2009;27(5):578-83
88. Bhat J, Rane R, Solapure SM, et al. High-throughput screening of RNA polymerase inhibitors using a fluorescent UTP analog. J Biomol Screen 2006;11(8):968-76 (Pubitemid 44847151)
89. Muramatsu Y, Ishii MM, Inukai M. Studies on novel bacterial translocase I inhibitors, A-500359s. II. Biological activities of A-500359 A, C, D and G. J Antibiot (Tokyo) 2003;56(3):253-8 (Pubitemid 36443393)
90. White EL, Southworth K, Ross L, et al. A novel inhibitor of Mycobacterium tuberculosis pantothenate synthetase. J Biomol Screen 2007;12(1):100-5 (Pubitemid 46224924)
91. Rawat R, Whitty A, Tonge PJ. The isoniazid-NAD adduct is a slow, tight-binding inhibitor of InhA, the Mycobacterium tuberculosis enoyl reductase: adduct affinity and drug resistance. Proc Natl Acad Sci U S A 2003;100(24):13881-6 (Pubitemid 37499160)
92. Banerjee A, Dubnau E, Quemard A, et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 1994;263(5144):227-30 (Pubitemid 24067929)
93. Kuo MR, Morbidoni HR, Alland D, et al. Targeting Tuberculosis and Malaria through inhibition of enoyl reductase. J Biol Chem 2003;278(23):20851-9
94. Parish T, Stoker NG. Development and use of a conditional antisense mutagenesis system in mycobacteria. FEMS Microbiol Lett 1997;1):154:151-7 (Pubitemid 27376750)
95. Blokpoel MC, Murphy HN, OToole R, et al. Tetracycline-inducible gene regulation in mycobacteria. Nucleic Acids Res 2005;33(2):e22
96. Ehrt S, Guo XV, Hickey CM, et al. Controlling gene expression in mycobacteria with anhydrotetracycline and Tet repressor. Nucleic Acids Res 2005;33(2):e21
97. Wu S, Howard ST, Lakey DL, et al. The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis in vivo. Mol Microbiol 2004;51(6):1551-62 (Pubitemid 38406531)
98. Forsyth RA, Haselbeck RJ, Ohlsen KL, et al. A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol 2002;43(6):1387-400 (Pubitemid 34595533)
99. Ji Y, Zhang B, Van SF, et al. Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA. Science 2001;293(5538):2266-9 (Pubitemid 32900238)
100. Wang B, Kuramitsu HK. Inducible antisense RNA expression in the characterization of gene functions in Streptococcus mutans. Infect Immun 2005;73(6):3568-76 (Pubitemid 40745901)
101. Ji Y, Yin D, Fox B, et al. Validation of antibacterial mechanism of action using regulated antisense RNA expression in Staphylococcus aureus. FEMS Microbiol Lett 2004;231(2):177-84 (Pubitemid 38251597)
102. Ondeyka JG, Zink DL, Young K, et al. Discovery of bacterial fatty acid synthase inhibitors from a Phoma species as antimicrobial agents using a new antisense-based strategy. J Nat Prod 2006;69(3):377-80
103. Wang J, Kodali S, Lee SH, et al. Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties. Proc Natl Acad Sci USA 2007;104(18):7612-16 (Pubitemid 47185954)
104. Wang J, Soisson SM, Young K, et al. Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature 2006;441(7091):358-61 (Pubitemid 44050201)
105. Young K, Jayasuriya H, Ondeyka JG, et al. Discovery of FabH/FabF inhibitors from natural products. Antimicrob Agents Chemother 2006;50(2):519-26 (Pubitemid 43190961)
106. Nisa S, Blokpoel MC, Robertson BD, et al. Targeting the chromosome partitioning protein ParA in tuberculosis drug discovery. J Antimicrob Chemother 2010;65(11):2347-58
107. Tehan BG, Lloyd EJ, Wong MG. Molecular field analysis of clozapine analogs in the development of a pharmacophore model of antipsychotic drug action. J Mol Graph Model 2001;19(5):417-26.68
108. Available from http://pubchem.ncbi.nlm. nih.gov/.NCBI Pubchem database 2011
109. Kauppi AM, Nordfelth R, Uvell H, et al. Targeting bacterial virulence: inhibitors of type III secretion in Yersinia. Chem Biol 2003;10(3):241-9 (Pubitemid 36380281)
110. Nordfelth R, Kauppi AM, Norberg HA, et al. Small-molecule inhibitors specifically targeting type III secretion. Infect Immun 2005;73(5):3104-14 (Pubitemid 40570380)
111. Hudson DL, Layton AN, Field TR, et al. Inhibition of type III secretion in Salmonella enterica serovar Typhimurium by small-molecule inhibitors. Antimicrob Agents Chemother 2007;51(7):2631-5 (Pubitemid 47047354)
112. Aiello D, Williams JD, Majgier-Baranowska H, et al. Discovery and characterization of inhibitors of Pseudomonas aeruginosa type III secretion. Antimicrob Agents Chemother. 2010;54(5):1988
113. Cole ST, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998;393(6685):537-44 (Pubitemid 28319235)
114. Available from: http://www.newtbdrugs. org/project.php?id=145.Working Group on New TB Drugs, Project Details SQ-609 2011
115. Dempsey SG. Developing a cell based screen for inhibitors of two component signal transduction in mycobacteria. Victoria University of Wellington; Wellington: 2009
116. McDevitt D, Payne DJ, Holmes DJ, et al. Novel targets for the future development of antibacterial agents. Symp Ser Soc Appl Microbiol 2002;92(31):28S-34S (Pubitemid 34535503)
117. Clatworthy AE, Pierson E, Hung DT. Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 2007;3(9):541-8 (Pubitemid 47294400)
118. Geddes AM, Klugman KP, Rolinson GN. Introduction: historical perspective and development of amoxicillin/clavulanate. Int J Antimicrob Agents 2007;30(S2):109-12 (Pubitemid 350110387)
119. Van Bambeke F, Glupczynski Y, Plesiat P, et al. Antibiotic efflux pumps in prokaryotic cells: occurrence, impact on resistance and strategies for the future of antimicrobial therapy. J Antimicrob Chemother 2003;51(5):1055-65 (Pubitemid 36622059)
120. Marquez B. Bacterial efflux systems and efflux pumps inhibitors. Biochimie 2005;87(12):1137-47 (Pubitemid 41572643)
121. Lomovskaya O, Warren MS, Lee A, et al. Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy. Antimicrob Agents Chemother 2001;45(1):105-16 (Pubitemid 32039101)
122. Ainsa JA, Blokpoel MC, Otal I, et al. Molecular cloning and characterization of Tap, a putative multidrug efflux pump present in Mycobacterium fortuitum and Mycobacterium tuberculosis. J Bacteriol 1998;180(22):5836-43 (Pubitemid 28514198)
123. Ramon-Garcia S, Martin C, De Rossi E, et al. Contribution of the Rv2333c efflux pump (the Stp protein) from Mycobacterium tuberculosis to intrinsic antibiotic resistance in Mycobacterium bovis BCG. J Antimicrob Chemother 2007;59(3):544-7 (Pubitemid 47073463)
124. Silva PE, Bigi F, de la Paz Santangelo M, et al. Characterization of P55, a multidrug efflux pump in Mycobacterium bovis and Mycobacterium tuberculosis. Antimicrob Agents Chemother 2001;45(3):800-4 (Pubitemid 32182029)
125. Rojas A, Hernandez L, Pereda-Miranda R, et al. Screening for antimicrobial activity of crude drug extracts and pure natural products from Mexican medicinal plants. J Ethnopharmacol 1992;35(3):275-83
126. Petersen F, Amstutz R, Koehn FE. High impact technologies for natural products screening. Natural compounds as drugs. Volume I Birkhauser, Basel p. 175-210
127. Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nat Rev Drug Discov 2005;4(3):206-20 (Pubitemid 40372555)
128. Stewart GR, Patel J, Robertson BD, et al. Mycobacterial mutants with defective control of phagosomal acidification. PLoS Pathog 2005;1(3):269-78
129. OBrien J, Wilson I, Orton T, et al. Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem 2000;267(17):5421-6
130. Ansar Ahmed S, Gogal RM Jr, Walsh JE. A new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes: an alternative to [3H] thymidine incorporation assay. J Immunol Methods 1994;170(2):211-24 (Pubitemid 24122510)
131. Prouty MG, Correa NE, Barker LP, et al. Zebrafish-Mycobacterium marinum model for mycobacterial pathogenesis. FEMS Microbiol Lett 2003;225(2):177-82 (Pubitemid 38373387)
132. Swaim LE, Connolly LE, Volkman HE, et al. Mycobacterium marinum infection of adult Zebrafish causes caseating granulomatous tuberculosis and is moderated by adaptive immunity. Infect Immun 2006;74(11):6108-17 (Pubitemid 44657389)
133. Gao L-Y, Guo S, McLaughlin B, et al. A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT-6 secretion. Mol Microbiol 2004;53(6):1677-93 (Pubitemid 39265314)
134. Clay H, Davis JM, Beery D, et al. Dichotomous role of the macrophage in early Mycobacterium marinum infection of the Zebrafish. Cell Host Microbe 2007;2(1):29-39 (Pubitemid 47010243)
135. van der Sar AM, Spaink HP, Zakrzewska A, et al. Specificity of the zebrafish host transcriptome response to acute and chronic mycobacterial infection and the role of innate and adaptive immune components. Mol Immunol 2009;46(11-12):2317-32
136. Volkman HE, Clay H, Beery D, et al. Tuberculous granuloma formation is enhanced by a Mycobacterium virulence determinant. PLoS Biol 2004;2(11):e367
137. Cosma CL, Klein K, Kim R, et al. Mycobacterium marinum Erp is a virulence determinant required for cell wall integrity and intracellular survival. Infect Immun 2006;74(6):3125-33 (Pubitemid 43794501)
138. Meijer AH, Verbeek FJ, Salas-Vidal E, et al. Transcriptome profiling of adult zebrafish at the late stage of chronic tuberculosis due to Mycobacterium marinum infection. Mol Immunol 2005;42(10):1185-203
139. Payne DJ, Gwynn MN, Holmes DJ, et al. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 2007;6(1):29-40 (Pubitemid 46020284)
140. Koul A, Arnoult E, Lounis N, et al. The challenge of new drug discovery for tuberculosis. Nature 2011;469(7331):483-90
141. Projan SJ. Why is big Pharma getting out of antibacterial drug discovery? Curr Opin Microbiol 2003;6(5):427-30 (Pubitemid 37345405)
142. Mra Y. Inhibitors as novel antibacterial agents. Curr Top Med Chem 2005;5:1221-36
143. Hoshino K, Inoue K, Murakami Y, et al. In vitro and in vivo antibacterial activities of DC-159a, a new fluoroquinolone. Antimicrob Agents Chemother 2007;2007:AAC.00853-07
144. Makarov V, Manina G, Mikusova K, et al. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science 2009;324(5928):801-4
145. Williams KN, Stover CK, Zhu T, et al. Promising antituberculosis activity of the oxazolidinone PNU-100480 relative to that of linezolid in a murine model. Antimicrob Agents Chemother 2009;53(4):1314-19
146. Protopopova M, Hanrahan C, Nikonenko B, et al. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines. J Antimicrob Chemother 2005;56(5):968-74 (Pubitemid 41631930)
147. Koul A, Arnoult E, Lounis N, et al. The challenge of new drug discovery for tuberculosis. Nature 2011;469(7331):483-90
148. Stover CK, Warrener P, VanDevanter DR, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 2000;405(6789):962-6 (Pubitemid 30435054)
149. Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005;307(5707):223-7 (Pubitemid 40116230)
150. 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(11):e466
151. Barbachyn MR, Hutchinson DK, Brickner SJ, et al. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. J Med Chem 1996;39(3):680-5 (Pubitemid 26069690)
152. Miyazaki E, Miyazaki M, Chen JM, et al. Moxifloxacin (BAY12-8039), a new 8-methoxyquinolone, is active in a mouse model of tuberculosis. Antimicrob Agents Chemother 1999;43(1):85-9 (Pubitemid 29069204)
153. Tomioka H, Sato K, Akaki T, et al. Comparative in vitro antimicrobial activities of the newly synthesized quinolone HSR-903, sitafloxacin (DU- 6859a), gatifloxacin (AM-1155), and levofloxacin against mycobacterium tuberculosis and mycobacterium avium complex. Antimicrob Agents Chemother 1999;43(12):3001-4
154. Tsukamura M, Mizuno S, Toyama H. In-vitro antimycobacterial activity of rifapentine (comparison with rifampicin). Kekkaku 1986;61(12):633-9 (Pubitemid 17233059)
155. Global Alliance for TB Drug Development. Handbook of anti-tuberculosis agents. Tuberculosis (Edinb) 2008;88(2):85-6
156. Bogatcheva E, Hanrahan C, Chen P, et al. Discovery of dipiperidines as new antitubercular agents. Bioorganic Med Chem Lett 2010;20(1):201-5
157. Reddy VM, Einck L, Nacy CA. Capuramycin analogues: characterization of in vitro antimycobacterial activities. Antimicrob Agents Chemother 2007;52(2):719-21