The magic bullets and tuberculosis drug targets

Annual Review of Pharmacology and Toxicology

Volumn 45, Issue , 2005, Pages 529-564

  Zhang, Ying ^a  

^a JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Antituberculosis agents; Drug development; Mycobacterium tuberculosis

Indexed keywords

2 NITROIMIDAZOLE; 4 NITROIMIDAZOLE; 6,7 DIHYDRO 2 NITRO 6 (4 TRIFLUOROMETHOXYBENZYLOXY) 5H IMIDAZO[2,1 B][1,3]OXAZINE; CHLORPROMAZINE; CLOFAZIMINE; CYCLOSERINE; ETHAMBUTOL; ETHIONAMIDE; FURAZOLIDONE; GATIFLOXACIN; ISONIAZID; KANAMYCIN; LINEZOLID; MICONAZOLE; MOXIFLOXACIN; NICLOSAMIDE; NITROFURAN DERIVATIVE; OXAZOLIDINEDIONE DERIVATIVE; PEPTIDE DEFORMYLASE INHIBITOR; PHENOTHIAZINE DERIVATIVE; PYRAZINAMIDE; QUINOLINE DERIVED ANTIINFECTIVE AGENT; QUINOLONE DERIVATIVE; RIFABUTIN; RIFALAZIL; RIFAMPICIN; SIGMA FACTOR; STREPTOMYCIN; TUBERCULOSTATIC AGENT; U 100480; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRULENCE FACTOR;

BACTERIAL CELL WALL; BACTERICIDAL ACTIVITY; CHEMOTHERAPY; DRUG MECHANISM; DRUG SCREENING; DRUG TARGETING; ENZYME INHIBITION; GENOMICS; HUMAN; MULTIDRUG RESISTANCE; MYCOBACTERIUM TUBERCULOSIS; NUCLEIC ACID SYNTHESIS; PRIORITY JOURNAL; REVIEW; TARGET CELL; TUBERCULOSIS;

ANIMALS; ANTITUBERCULAR AGENTS; DRUG DELIVERY SYSTEMS; HUMANS; MYCOBACTERIUM TUBERCULOSIS; TUBERCULOSIS;

BACILLI; BACTERIA (MICROORGANISMS); MYCOBACTERIUM; MYCOBACTERIUM TUBERCULOSIS;

EID: 13844319812     PISSN: 03621642     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.pharmtox.45.120403.100120     Document Type: Review

References (235)

1. Ryan F. 1993. The Forgotten Plague. How the Battle against Tuberculosis Was Won and Lost, p. 3. Boston: Little, Brown. 460 pp.
2. World Health Organization. 2003. The World Health Organization Global Tuberculosis Program. http://www.who.int/gtb/
3. Center for Disease Control. 1993. Outbreak of multidrug-resistant tuberculosis at a hospital-New York City. 1991. Morb. Mortal. Wkly. Rep. 42:427,433-34
4. Kimerling ME, Kluge H, Vezhnina N, Iacovazzi T, Demeulenaere T, et al. 1999. Inadequacy of the current WHO re-treatment regiment in central Siberian prisons: treatment failure and MDR-TB. Int. J. Tuberc. Lung Dis. 3:451-53
5. De Cock KM, Chaisson RE. 1999. Will DOTS do it? A reappraisal of tuberculosis control in countries with high rates of HIV infection. Int. J. Tuberc. Lung Dis. 3:457-65
6. Tuberculosis: a global emergency. 1993. World Health Forum 14:438
7. Global Alliance for Tuberculosis Drug Development. 2001. Scientific blueprint for TB drug development. Tuberculosis 81(Suppl.):1-52
8. Smith CV, Sharma V, Sacchettini JC. 2004. TB drug discovery: addressing issues of persistence and resistance. Tuberculosis 84:45-55
9. Duncan K. 2003. Progress in TB drug development and what is still needed. Tuberculosis 83:201-7
10. Kremer LS, Besra GS. 2002. Current status and future development of antitubercular chemotherapy. Expert. Opin. Investig. Drugs 11:1033-49
11. Zhang Y, Amzel LM. Tuberculosis drug targets. Curr. Drug Targets 3:131-54
12. Barry CE 3rd. 2001. Preclinical candidates and targets for tuberculosis therapy. Curr. Opin. Investig. Drugs 2:198-201
13. Inderlied CB, Salfinger M. 1999. Antimycobacterial agents and susceptibility tests. In Manual of Clinical Microbiology, ed. PR Murray, EJ Baron, MA Pfaller, FC Tenover, RH Yolken, pp. 1601-1623. Washington DC: ASM Press. 7th ed.
14. Domagk G. 1935. Ein Beitrag zur Chemotherapie der bakteriellen Infektionen. Deutschemedizinische Wochenschrift 61:250-53
15. Hatfull G, Jacobs WR Jr, eds. 2000. Molecular Genetics of Mycobacteria. Washington DC: ASM Press
16. Deleted in proof
17. Schatz AB, Bugie E, Waksman S. 1944. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc. Soc. Exp. Biol. Med. 55:66-69
18. Rich A, Follis RH. 1938. The inhibitory effect of sulfanilamide on the development of experimental tuberculosis of the guinea pig. Bull. Johns Hopkins Hosp. 62:77-84
19. Hinshaw HC, McDermott W. 1950. Thiosemicarbazone therapy of tuberculosis in human. Am. Rev. Tuberc. 61:145-57
20. Lehmann J. 1946. p-aminosalicylic acid in the treatment of tuberculosis. Lancet 1:15-16
21. Bernheim F. 1940. The effect of salicylate on the oxygen uptake of the tubercle bacillus. Science 92:204
22. Chorine V. 1945. Action de l'amide nicotinique sur les bacilles du genre Mycobacterium. C. R. Acad. Sci. 220:150-51
23. Bernstein J, Lott WA, Steinberg BA, Yale HL. 1952. Chemotherapy of experimental tuberculosis. V. Isonicotinic acid hydrazide (Nydrazid) and related compounds. Am. Rev. Tuberc. 65:357-64
24. Fox H. 1952. The chemical approach to the control of tuberculosis. Science 116: 129-34
25. Offe HA, Siefken W, Domagk G. 1952. The tuberculostatic activity of hydrazine derivatives from pyridine carboxylic acids and carbonyl compounds. Z. Naturfobrsch. 7b:462-68
26. nd ed.
27. Malone L, Schurr A, Lindh H, McKenzie D, Kiser JS, Williams JH. 1952. The effect of pyrazinamide (Aldinamide) on experimental tuberculosis in mice. Am. Rev. Tuberc. 65:511-18
28. Liebermann D, Moyeux M, Rist N, Grumbach F. 1956. Sur la preparation de nouveaux thioamides pyridiniques acitifs dans la tuberculose experimentale. C. R. Acad. Sci. 242:2409-12
29. Thomas JP, Baughn CO, Wilkinson RG, Shepherd RG. 1961. A new synthetic compound with antituberculous activity in mice: ethambutol (dextro-2, 2′-(ethylenediimino)-di-butanol). Am. Rev. Respir. Dis. 83:891-93
30. Kurosawa H. 1952. Studies on the antibiotic substances from actinomyces. XXIII. The isolation of an antibiotic produced by a strain of Streptomyces "K 30". J. Antibiot. Ser. B 5:682-88
31. Umezawa H, Ueda M, Maeda K, Yagishita K, Kondo S, et al. 1957. Production and isolation of a new antibiotic, kanamycin. J. Antibiot. Jpn. Ser. A 10:181-88
32. Bartz QR, Ehrlich J, Mold JD, Penner MA, Smith RM. 1951. Viomycin, a new tuberculostatic antibiotic. Am. Rev. Tuberc. 63:4-6
33. Herr EB Jr, Haney ME, Pittenger GE, Higgens CE. 1960. Isolation and characterization of a new peptide antibiotic. Proc. Indiana Acad. Sci. 69:134
34. Sensi P, Margalith P, Timbal MT. 1959. Rifomycin, a new antibiotic. Preliminary report. Il. Farmaco. Sci. 14:146-47
35. Maggi N, Pasqualucci CR, Ballotta R, Sensi P. 1966. Rifampicin: a new orally active rifamycin. Farmaco. Sci. 21:68-75
36. Deitz WH, Bailey JH, Froelich EJ. 1963. In vitro antibacterial properties of nalidixic acid, a new drug active against gram-negative organisms. Antimicrob. Agents Chemother. 161:583-87
37. Tsunekawa HMT, Nakamura E, Tsukamura M, Amano H. 1987. Therapeutic effect of ofloxacin on 'treatment-failure' pulmonary tuberculosis. Kekkaku 62:435-39
38. Yew WW, Kwan SY, Ma WK, Khin MA, Chau PY. 1990. In-vitro activity of ofloxacin against Mycobacterium tuberculosis and its clinical efficacy in multiply resistant pulmonary tuberculosis. J. Antimicrob. Chemother. 26:227-36
39. Fox W, Ellard GA, Mitchison DA. 1999. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. Int. J. Tuberc. Lung Dis. 3(10 Suppl. 2):S231-79
40. Canetti G. 1955. The Tubercle Bacillus in the Pulmonary Lesion of Man. New York: Springer
41. Zhang Y. 2004. Persistent and dormant tubercle bacilli and latent tuberculosis. Front. Biosci. 9:1136-56
42. nd ed.
43. Flynn JL, Chan J. 2001. Tuberculosis: latency and reactivation. Infect. Immun. 69:4195-201
44. Mitchison D. 1979. Basic mechanisms of chemotherapy. Chest 76(6 Suppl.):771-81
45. Zhang Y, Mitchison DA. 2003. The curious characteristics of pyrazinamide: a review. Int. J. Tuberc. Lung Dis. 7:6-21
46. Wade MM, Zhang Y. 2004. Mechanisms of drug resistance in Mycobacterium tuberculosis. Front. Biosci. 9:975-94
47. Zhang Y, Jacobs WR Jr, Vilcheze C. 2004. Mechanisms of drug resistance in Mycobacterium tuberculosis. In Pathogenesis of Tuberculosis. Washington, DC: ASM Press. 2nd ed.
48. Zhang Y, Heym B, Allen B, Young D, Cole S. 1992. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 358:591-93
49. Winder FG, Collins PB. 1970. Inhibition by isoniazid of synthesis of mycolic acids in Mycobacterium tuberculosis. J. Gen. Microbiol. 63:41-48
50. Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, et al. 1994. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263:227-30
51. Rozwarski DA, Grant GA, Barton DH, Jacobs WR Jr, Sacchettini JC. 1998. Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science 279:98-102
52. Broussy S, Coppel Y, Nguyen M, Bernadou J, Meunier B. 2003. 1H and 13C NMR characterization of hemiamidal isoniazid-NAD(H) adducts as possible inhibitors of InhA reductase of Mycobacterium tuberculosis. Chemistry 9:2034-38
53. Winder F. 1982. Mode of action of the antimycobacterial agents and associated aspects of the molecular biology of mycobacteria. In The Biology of Mycobacteria, ed. C Ratledge, J Stanford, pp. 354-438. New York: Academic
54. Winder F, Collins P. 1968. The effect of isoniazid on nicotinamide nucleotide levels in Mycobacterium bovis strain BCG. Am. Rev. Respir. Dis. 97:719-20
55. Sriprakash KS, Ramakrishnan T. 1969. Isoniazid and nicotinamide adenine dinucleotide synthesis in M. tuberculosis. Indian J. Biochem. 6:49-50
56. Miesel L, Weisbrod T, Marcinkeviciene JA, Bittman R, Doshi P, et al. 1998. NADH dehydrogenase defects confer resistance to isoniazid and conditional lethality in Mycobacterium smegmatis. J. Bacteriol. 180:2459-67
57. Lee AS, Teo AS, Wong SY. 2001. Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates. Antimicrob. Agents Chemother. 45:2157-59
58. DeBarber AE, Mdluli K, Bosman M, Bekker LG, Barry CE 3rd. 2000. Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 97:9677-82
59. Baulard AR, Betts JC, Engohang-Ndong J, Quan S, McAdam RA, et al. 2000. Activation of the pro-drug ethionamide is regulated in mycobacteria. J. Biol. Chem. 275:28326-31
60. Vannelli TA, Dykman A, Ortiz de Montellano PR. 2002. The antituberculosis drug ethionamide is activated by a flavoprotein monooxygenase. J. Biol. Chem. 277:12824-29
61. Morlock GP, Metchock B, Sikes D, Crawford JT, Cooksey RC. 2003. ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. Antimicrob. Agents Chemother. 47:3799-805
62. Takayama K, Kilburn JO. 1989. Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis. Antimicrob. Agents Chemother. 33:1493-99
63. Mikusov K, Slayden RA, Besra GS, Brennan P. 1995. Biogenesis of the mycobacterial cell wall and the site of action of ethambutol. Antimicrob. Agents Chemother. 39:2484-89
64. Wolucka BA, McNeil MR, de Hoffmann E, Chojnacki T, Brennan PJ. 1994. Recognition of the lipid intermediate for arabinogalactan/arabinomannan biosynthesis and its relation to the mode of action of ethambutol on mycobacteria. J. Biol. Chem. 269:23328-35
65. Telenti A, Philipp W, Sreevatsan S, Bernasconi C, Stockbauer KE, et al. 1997. The emb operon, a unique gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat. Med. 3:567-70
66. Belanger AE, Besra GS, Ford ME, Mikusov K, Belisle JT, et al. 1996. The embA genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc. Natl. Acad. Sci. USA 93:11919-24
67. Sreevatsan S, Stockbauer KE, Pan X, Kreiswirth BN, Moghazeh SL, et al. 1997. Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations. Antimicrob. Agents Chemother. 41:1677-81
68. David HL, Takayama K, Goldman DS. 1969. Susceptibility of mycobacterial D-alanyl-D-alanine synthetase to D-cycloserine. Am. Rev. Respir. Dis. 100: 579-81
69. Strych U, Penland RL, Jimenez M, Krause KL, Benedik MJ. 2001. Characterization of the alanine racemases from two mycobacteria. FEMS Microbiol. Lett. 196:93-98
70. Caceres NE, Harris NB, Wellehan JF, Feng Z, Kapur V, et al. 1997. Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine in Mycobacterium smegmatis. J. Bacteriol. 179:5046-55
71. Chacon O, Feng Z, Harris NB, Caceres NE, Adams LG, et al. 2002. Mycobacterium smegmatis D-alanine race-mase mutants are not dependent on D-alanine for growth. Antimicrob. Agents Chemother. 46:47-54
72. Belanger AE, Porter JC, Hatfull GF. 2000. Genetic analysis of peptidoglycan biosynthesis in mycobacteria: characterization of a ddlA mutant of Mycobacterium smegmatis. J. Bacteriol. 182:6854-56
73. Feng Z, Barletta RG. 2003. Roles of Mycobacterium smegmatis D-alanine:D-alanine ligase and D-alanine racemase in the mechanisms of action of and resistance to the peptidoglycan inhibitor D-cycloserine. Antimicrob. Agents Chemother. 47:283-91
74. Mitchison DA. 1985. The action of antituberculosis drugs in short course chemotherapy. Tubercle 66:219-25
75. Telenti A, Imboden P, Marchesi F, Lowrie D, Cole ST, et al. 1993. Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet 341:647-50
76. Jarvis B, Lamb HM. 1998. Rifapentine. Drugs 56:607-16
77. Williams DL, Spring L, Collins L, Miller LP, Heifets LB, et al. 1998. Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 42:1853-57
78. Andersson MI, MacGowan AP. 2003. Development of the quinolones. J. Antimicrob. Chemother. 51(Suppl. 1):1-11
79. Jacobs M. 1999. Activity of quinolones against mycobacteria. Drugs 58(Suppl. 2):19-22
80. Grimaldo ER, Tupasi TE, Rivera AB, Quelapio MI, Cardano RC, et al. 2001. Increased resistance to ciprofloxacin and ofloxacin in multidrug-resistant Mycobacterium tuberculosis isolates from patients seen at a tertiary hospital in the Philippines. Int. J. Tuberc. Lung Dis. 5:546-50
81. Tuberculosis Research Centre C. 2002. Shortening short course chemotherapy: a randomised clinical trial for treatment of smear positive pulmonary tuberculosis with regimens using ofloxacin in the intensive phase. Indian J. Tuberc. 49:27-38
82. Takiff HE, Salazar L, Guerrero C, Philipp W, Huang WM, et al. 1994. Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob. Agents Chemother. 38:773-80
83. Kocagoz T, Hackbarth CJ, Unsal I, Rosenberg EY, Nikaido H, et al. 1996. Gyrase mutations in laboratory selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37Ra. Antimicrob. Agents Chemother. 40:1768-74
84. Spotts CR, Stanier RY. 1961. Mechanism of streptomycin action on bacteria: a unitary hypothesis. Nature 192:633-37
85. Davies J, Gorini L, Davis BD. 1965. Misreading of RNA codewords induced by aminoglycoside antibiotics. Mol. Pharmacol. 1:93-106
86. Anand N, Davis BD. 1960. Effect of streptomycin on Escherichia coli. Nature 185:22-23
87. Garvin RT, Biswas DK, Gorini L. 1974. The effects of streptomycin or dihydrostreptomycin binding to 16S RNA or to 30S ribosomal subunits. Proc. Natl. Acad. Sci. USA 71:3814-18
88. Finken M, Kirschner P, Meier A, Wrede A, Bottger EC. 1993. Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot. Mol. Microbiol. 9: 1239-46
89. Zhang Y, Telenti A. 2000. Genetics of drug resistance in Mycobacterium tuberculosis. See Ref. 15, pp. 235-54
90. Alangaden GJ, Kreiswirth BN, Aouad A, Khetarpal M, Igno FR, et al. 1998. Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 42:1295-97
91. Suzuki Y, Katsukawa C, Tamaru A, Abe C, Makino M, et al. 1998. Detection of kanamycin-resistant Mycobacterium tuberculosis by identifying mutations in the 16S rRNA gene. J. Clin. Microbiol. 36:1220-25
92. Taniguchi H, Chang B, Abe C, Nikaido Y, Mizuguchi Y, et al. 1997. Molecular analysis of kanamycin and viomycin resistance in Mycobacterium smegmatis by use of the conjugation system. J. Bacteriol. 179:4795-801
93. Kruuner A, Jureen P, Levina K, Ghebremichael S, Hoffner S. 2003. Discordant resistance to kanamycin and amikacin in drug-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 47:2971-73
94. Scorpio A, Zhang Y. 1996. Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nat. Med. 2:662-67
95. Scorpio A, Lindholm-Levy P, Heifets L, Gilman R, Siddiqi S, et al. 1997. Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 41:540-43
96. Tarshis MS, Weed WA. 1953. Lack of significant in vitro sensitivity of Mycobacterium tuberculosis to pyrazinamide on three different solid media. Am. Rev. Tuberc. 67:391-95
97. McDermott W, Tompsett R. 1954. Activation of pyrazinamide and nicotinamide in acidic environment in vitro. Am. Rev. Tuberc. 70:748-54
98. Zhang Y, Permar S, Sun Z. 2002. Conditions that may affect the results of Mycobacterium tuberculosis susceptibility testing to pyrazinamide. J. Med. Microbiol. 51:42-49
99. Wade MM, Zhang Y. 2004. Anaerobic incubation conditions enhances the activity of anti-tuberculosis drug pyrazinamide. J. Med. Microbiol. 53:769-73
100. Zhang Y, Scorpio A, Nikaido H, Sun ZH. 1999. Role of acid pH and deficient efflux of pyrazinoic acid in the unique susceptibility of Mycobacterium tuberculosis to pyrazinamide. J. Bacteriol. 181:2044-49
101. Zhang Y, Wade MM, Scorpio A, Zhang H, Sun Z. 2003. Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid. J. Antimicrob. Chemother. 52:790-95
102. Okunade AL, Elvin-Lewis MP, Lewis WH. 2004. Natural antimycobacterial metabolites: current status. Phytochemistry 65:1017-32
103. Alvirez-Freites EJ, Carter JL, Cynamon MH. 2002. In vitro and in vivo activities of gatifloxacin against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 46:1022-25
104. Rodriguez GM, Smith I. 2003. Mechanisms of iron regulation in mycobacteria: role in physiology and virulence. Mol. Microbiol. 47:1485-94
105. Ji B, Lounis N, Maslo C, Truffot-Pernot C, Bonnafous P, et al. 1998. In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 42:2066-69
106. Miyazaki E, Miyazaki M, Chen JM, Chaisson RE, Bishai WR. 1999. Moxifloxacin (BAY12-8039), a new 8-methoxyquinolone, is active in a mouse model of tuberculosis. Antimicrob. Agents Chemother. 43:85-89
107. Hu Y, Coates AR, Mitchison DA. 2003. Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 47:653-57
108. Nuermberger EL, Yoshimatsu T, Tyagi S, O'Brien RJ, Vernon AN, et al. 2004. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am. J. Respir. Crit. Care Med. 169:421-26
109. Grosset J, Truffot-Pernot C, Lacroix C, Ji B. 1992. Antagonism between isoniazid and the combination pyrazinamide-rifampin against tuberculosis infection in mice. Antimicrob. Agents Chemother. 36:548-51
110. American Thoracic Society. 2001. Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations-United States, 2001. Am. J. Respir. Crit. Care Med. 164:1319-20
111. Pletz MW, De Roux A, Roth A, Neumann KH, Mauch H, et al. 2004. Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study. Antimicrob. Agents Chemother. 48:780-82
112. Valerio G, Bracciale P, Manisco V, Quitadamo M, Legari G, et al. 2003. Long-term tolerance and effectiveness of moxifloxacin therapy for tuberculosis: preliminary results. J. Chemother. 15:66-70
113. Hirata T, Saito H, Tomioka H, Sato K, Jidoi J, et al. 1995. In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 39:2295-303
114. Shoen CM, DeStefano MS, Cynamon MH. 2000. Durable cure for tuberculosis: rifalazil in combination with isoniazid in a murine model of Mycobacterium tuberculosis infection. Clin. Infect. Dis. 30(Suppl. 3):S288-90
115. Bodmer T, Zurcher G, Imboden P, Telenti A. 1995. Mutation position and type of substitution in the beta-subunit of the RNA polymerase influence in-vitro activity of rifamycins in rifampicin-resistant Mycobacterium tuberculosis. J. Antimicrob. Chemother. 35:345-48
116. Moghazeh SL, Pan X, Arain T, Stover CK, Musser JM, et al. 1996. Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations. Antimicrob. Agents Chemother. 40:2655-57
117. Dietze R, Teixeira L, Rocha LM, Palaci M, Johnson JL, et al. 2001. Safety and bactericidal activity of rifalazil in patients with pulmonary tuberculosis. Antimicrob. Agents Chemother. 45:1972-76
118. Barrett J. 2000. Linezolid Pharmacia Corp. Curr. Opin. Investig. Drugs 1:181-87
119. Barbachyn MR, Hutchinson DK, Brickner SJ, Cynamon MH, Kilburn JO, et al. 1996. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. J. Med. Chem. 39:680-85
120. Oxazolidinones, a new class of synthetic antituberculosis agent. In vitro and in vivo activities of DuP-721 against Mycobacterium tuberculosis. Diagn. Microbiol. Infect. Dis. 14:465-71
121. Zurenko GE, Yagi BH, Schaadt RD, Allison JW, Kilburn JO, et al. 1996. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob. Agents Chemother. 40:839-45
122. Cynamon MH, Klemens SP, Sharpe CA, Chase S. 1999. Activities of several novel oxazolidinones against Mycobacterium tuberculosis in a murine model. Antimicrob. Agents Chemother. 43:1189-91
123. Sbardella G, Mai A, Artico M, Loddo R, Setzu MG, et al. 2004. Synthesis and in vitro antimycobacterial activity of novel 3-(1H-pyrrol-1-yl)-2- oxazolidinone analogues of PNU-100480. Bioorg. Med. Chem. Lett. 14:1537-11
124. Sun Z, Zhang Y. 1999. Antituberculosis activity of certain antifungal and antihelmintic drugs. Tuberc. Lung Dis. 79:319-20
125. Cole STR, Brosch J, Parkhill T, Garnier C, Churcher D, et al. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537-44
126. Aoyama Y, Horiuchi T, Gotoh O, Noshiro M, Yoshida Y. 1998. CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51. J. Biochem. 124:694-96
127. Guardiola-Diaz HM, Foster LA, Mushrush D, Vaz AD. 2001. Azole-antifungal binding to a novel cytochrome P450 from Mycobacterium tuberculosis: implications for treatment of tuberculosis. Biochem. Pharmacol. 61: 1463-70
128. McLean KJ, Marshall KR, Richmond A, Hunter IS, Fowler K, et al. Azole antifungals are potent inhibitors of cytochrome P450 mono-oxygenases and bacterial growth in mycobacteria and streptomycetes. Microbiology 148:2937-49
129. Bellamine A, Mangla AT, Nes WD, Waterman MR. 1999. Characterization and catalytic properties of the sterol 14alpha-demethylase from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 96:8937-42
130. Leys D, Mowat CG, McLean KJ, Richmond A, Chapman SK, et al. 2003. Atomic structure of Mycobacterium tuberculosis CYP121 to 1.06 A reveals novel features of cytochrome P450. J. Biol. Chem. 278:5141-47
131. Murugasu-Oei B, Dick T. 2000. Bactericidal activity of nitrofurans against growing and dormant Mycobacterium bovis BCG. J. Antimicrob. Chemother. 46:917-19
132. Wayne LG, Russell R. 1966. Selective effects of nitrofuraldoxime-anti on isoniazid resistant M. tuberculosis. Scand. J. Respir. Dis. 47:18-26
133. Barry VC, Belton JG, Conalty ML, Denney JM, Edward DW, et al. 1957. A new series of phenazines (rimino-compounds) with high antituberculosis activity. Nature 179:1013-15
134. Reddy VM, O'Sullivan JF, Gangadharam PR. 1999. Antimycobacterial activities of riminophenazines. J. Antimicrob. Chemother. 43:615-23
135. Steel HC, Matlola NM, Anderson R. 1999. Inhibition of potassium transport and growth of mycobacteria exposed to clofazimine and B669 is associated with a calcium-independent increase in microbial phospholipase A2 activity. J. Antimicrob. Chemother. 44:209-16
136. Bopape MC, Steel HC, Cockeran R, Matlola NM, Fourie PB, et al. 2004. Antimicrobial activity of clofazimine is not dependent on mycobacterial C-type phospholipases. J. Antimicrob. Chemother. 53: 971-74
137. Adams LB, Sinha I, Franzblau SG, Krahenbuhl JL, Mehta RT. 1999. Effective treatment of acute and chronic murine tuberculosis with liposome-encapsulated clofazimine. Antimicrob. Agents Chemother. 43:1638-43
138. van Rensburg CE, Joone GK, Sirgel FA, Matlola NM, O'Sullivan JF. 2000. In vitro investigation of the antimicrobial activities of novel tetramethylpiperidine-substituted phenazines against Mycobacterium tuberculosis. Chemotherapy 46:43-48
139. Amaral L, Kristiansen JE, Viveiros M, Atouguia J. 2001. Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy. J. Antimicrob. Chemother. 47:505-11
140. Salin FA, Kaushik NK, Sharma P, Choudary GV, Murthy PS, et al. 1991. Calmodulin-like activity in mycobacteria. Indian J. Biochem. Biophys. 28:491-95
141. Ordway D, Viveiros M, Leandro C, Bettencourt R, Almeida J, et al. 2003. Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 47:917-22
142. Amaral L, Kristiansen JE, Abebe LS, Millett W. 1996. Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: potential use for initial therapy of freshly diagnosed tuberculosis. J. Antimicrob. Chemother. 38:1049-53
143. Gadre DV, Talwar V. 1999. In vitro susceptibility testing of Mycobacterium tuberculosis strains to trifluoperazine. J. Chemother. 11:203-6
144. Crowle AJ, Douvas GS, May MH. 1992. Chlorpromazine: a drug potentially useful for treating mycobacterial infections. Chemotherapy 38:410-19
145. Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, et al. 2000. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 405:962-66
146. Ashtekar DR, Costa-Perira R, Nagrajan K, Vishvanathan N, Bhatt AD, et al. 1993. In vitro and in vivo activities of the nitroimidazole CGI 17341 against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 37:183-86
147. Nagarajan K, Shankar RG, Rajappa S, Shenoy SJ, Costa-Pereira R. 1989. Nitroimidazoles XXI 2,3-dihydro-6-nitroimidazo [2,1-b] oxazoles with antitubercular activity. Eur. J. Med. Chem. 24:631-33
148. Giglione C, Pierre M, Meinnel T. 2000. Peptide deformylase as a target for new generation, broad spectrum antimicrobial agents. Mol. Microbiol. 36:1197-205
149. Jones RN, Moet GJ, Sader HS, Fritsche TR. 2004. Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant gram-positive organism isolates. J. Antimicrob. Chemother. 53:804-7
150. Cynamon MH, Alvirez-Freites E, Yeo AE. 2004. BB-3497, a peptide deformylase inhibitor, is active against Mycobacterium tuberculosis. J. Antimicrob. Chemother. 53:403-5
151. Waller AS, Clements JM. 2002. Novel approaches to antimicrobial therapy: peptide deformylase. Curr. Opin. Drug Discov. Dev. 5:785-92
152. Azoulay-Dupuis E, Mohler J, Bedos JP. 2004. Efficacy of BB-83698, a novel peptide deformylase inhibitor, in a mouse model of pneumococcal pneumonia. Antimicrob. Agents Chemother. 48:80-85
153. Lofland D, Difuntorum S, Waller A, Clements JM, Weaver MK, et al. 2004. In vitro antibacterial activity of the peptide deformylase inhibitor BB-83698. J. Antimicrob. Chemother. 53:664-68
154. Chopra I, Hesse L, O'Neill AJ. 2002. Exploiting current understanding of antibiotic action for discovery of new drugs. J. Appl. Microbiol. 92(Suppl.):4S-15S
155. Dasgupta N, Kapur V, Singh KK, Das TK, Sachdeva S, et al. 2000. Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis. Tuber. Lung Dis. 80:141-59
156. Sherman DR, Voskuil M, Schnappinger D, Liao R, Harrell MI et al. 2001. Regulation of the M. tuberculosis hypoxic response gene alpha-crystallin. Proc. Natl. Acad. Sci. USA 98:7534-39
157. Park HD, Guinn KM, Harrell MI, Liao R, Voskuil MI, et al. 2003. Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol. Microbiol. 48:833-43
158. Boon C, Dick T. 2002. Mycobacterium bovis BCG response regulator essential for hypoxic dormancy. J. Bacteriol. 184:6760-67
159. Voskuil MI, Schnappinger D, Visconti KC, Harrell MI, Dolganov GM, Sherman DR, Schoolnik GK. 2003. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J. Exp. Med. 198:705-13
160. Cashel M, Gentry DR, Hernandez VJ, Vinella D. 1996. The stringent response. In Escherichia coli and Salmonella: Cellular and Molecular Biology, ed. FC Neidhardt, R Curtis, JL Ingraham, EC Lin, KB Low, et al., pp. 1488-96. Washington, DC: ASM Press
161. Primm TP, Andersen SJ, Mizrahi V, Avarbock D, Rubin H, et al. 2000. The stringent response of Mycobacterium tuberculosis is required for long-term survival. J. Bacteriol. 182:4889-98
162. Dahl JL, Kraus CN, Boshoff HI, Doan B, Foley K, et al. 2003. The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc. Natl. Acad. Sci. USA 100:10026-31
163. McKinney JD, Honer Zu, Bentrup K, Munoz-Elias EJ, Miczak A, Chen B, et al. 2000. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406:735-38
164. Wayne LG, Lin KY. 1982. Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions. Infect. Immun. 37:1042-49
165. Graham JE, Clark-Curtiss JE. 1999. Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS). Proc. Natl. Acad. Sci. USA 96:11554-59
166. Fenhalls G, Stevens L, Moses L, Bezuidenhout J, Betts JC, et al. 2002. In situ detection of Mycobacterium tuberculosis transcripts in human lung granulomas reveals differential gene expression in necrotic lesions. Infect. Immun. 70:6330-38
167. Sharma V, Sharma S, Hoener zu, Bentrup K, McKinney JD, Russell DG, et al. 2000. Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nat. Struct. Biol. 7:663-68
168. Glickman MS, Cox JS, Jacobs WR Jr. 2000. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol. Cell 5:717-27
169. Bardarov S, Kriakov J, Carriere C, Yu S, Vaamonde C, et al. 1997. Conditionally replicating mycobacteriophages: a system for transposon delivery to Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 94:10961-66
170. Pelicic V, Jackson M, Reyrat JM, Jacobs WR Jr, Gicquel B, et al. 1997. Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 94:10955-60
171. Jacobs WR Jr, Barletta R, Udani R, Chan J, Kalkut G, et al. Genetic systems for mycobacteria. Methods Enzymol. 204:537-55
172. Lamichhane G, Zignol M, Blades NJ, Geiman DE, Dougherty A, et al. 2003. A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: application to Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 100:7213-18
173. Sassetti CM, Boyd DH, Rubin EJ. 2001. Comprehensive identification of conditionally essential genes in mycobacteria. Proc. Natl. Acad. Sci. USA 98:12712-17
174. Sassetti CM, Boyd DH, Rubin EJ. 2003. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48:77-84
175. Manganelli R, Proveddi R, Rodrigue S, Beaucher J, Gaudreau L, et al. 2004. Sigma factors and global gene regulation in Mycobacterium tuberculosis. J. Bacteriol. 186:895-902
176. Doukhan L, Predich M, Nair G, Dussurget O, Mandic-Mulec I, et al. 1995. Genome organization of the mycobacterial sigma gene cluster. Gene 165:67-70
177. Wu S, Howard ST, Lakey DL, Kipnis A, Samten B, et al. 2004. The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis in vivo. Mol. Microbiol. 51:1551-62
178. Sun R, Converse PJ, Ko C, Tyagi S, Morrison NE, et al. 2004. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol. Microbiol. 52:25-38
179. Wu QL, Kong D, Lam K, Husson RN. 1997. A mycobacterial extracytoplasmic function sigma factor involved in survival following stress. J. Bacteriol. 179:2922-29
180. Raman S, Song T, Puyang X, Bardarov S, Jacobs WR Jr, et al. 2001. The alternative sigma factor SigH regulates major components of oxidative and heat stress responses in Mycobacterium tuberculosis. J. Bacteriol. 183:6119-25
181. Manganelli R, Voskuil MI, Schoolnik GK, Smith I. 2001. The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol. Microbiol. 41:423-37
182. Ando M, Yoshimatsu T, Ko C, Converse PJ, Bishai WR. 2003. Deletion of Mycobacterium tuberculosis sigma factor E results in delayed time to death with bacterial persistence in the lungs of aerosol-infected mice. Infect. Immun. 71:7170-72
183. Manganelli R, Fattorini L, Tan D, Iona E, Orefici G, et al. 2004. The extra cytoplasmic function sigma factor sigma(E) is essential for Mycobacterium tuberculosis virulence in mice. Infect. Immun. 72:3038-41
184. DeMaio J, Zhang Y, Ko C, Young DB, Bishai WR. 1996. A stationary-phase stress-response sigma factor from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 93:2790-94
185. Chen P, Ruiz RE, Li Q, Silver RF, Bishai WR. 2000. Construction and characterization of a Mycobacterium tuberculosis mutant lacking the alternate sigma factor gene, sigF. Infect. Immun. 68:5575-80
186. Alksne L. 2002. Virulence as a target for antimicrobial chemotherapy. Expert Opin. Investig. Drugs 11:1149-59
187. Smith I. 2003. Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin. Microbiol. Rev. 16:463-96
188. Sassetti CM, Rubin EJ. 2003. Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. USA 100:12989-94
189. Hoch J. 2000. Two-component and phosphorelay signal transduction. Curr. Opin. Microbiol. 3:165-70
190. Macielag MJ, Demers JP, Fraga-Spano SA, Hlasta DJ, Johnson SG, et al. 1998. Substituted salicylanilides as inhibitors of two-component regulatory systems in bacteria. J. Med. Chem. 41:2939-45
191. Macielag MJ, Goldschmidt R. 2000. Inhibitors of bacterial two-component signalling systems. Expert Opin. Investig. Drugs 9:2351-69
192. Barrett JF, Goldschmidt RM, Lawrence LE, Foleno B, Chen R, et al. 1998. Antibacterial agents that inhibit two-component signal transduction systems. Proc. Natl. Acad. Sci. USA 95:5317-22
193. Weidner-Wells MA, Ohemeng KA, Nguyen VN, Fraga-Spano S, Macielag MJ, et al. 2001. Amidino benzimidazole inhibitors of bacterial two-component systems. Bioorg. Med. Chem. Lett. 11: 1545-48
194. Stephenson K, Hoch JA. 2004. Developing inhibitors to selectively target two-component and phosphorelay signal transduction systems of pathogenic microorganisms. Curr. Med. Chem. 11:765-73
195. Sui Z, Guan J, Hlasta DJ, Macielag MJ, Foleno BD, et al. 1998. SAR studies of diaryltriazoles against bacterial two-component regulatory systems and their antibacterial activities. Bioorg. Med. Chem. Lett. 8:929-34
196. Deleted in proof
197. Via LE, Curcic R, Mudd MH, Dhandayuthapani S, Ulmer RJ, et al. 1996. Elements of signal transduction in Mycobacterium tuberculosis: in vitro phosphorylation and in vivo expression of the response regulator MtrA. J. Bacteriol. 178:3314-21
198. Supply P, Magdalena J, Himpens S, Locht C. 1997. Identification of novel intergenic repetitive units in a mycobacterial two-component system operon. Mol. Microbiol. 26:991-1003
199. Ewann F, Locht C, Supply P. 2004. Intracellular autoregulation of the Mycobacterium tuberculosis PrrA response regulator. Microbiology 150:241-46
200. Zahrt TC, Deretic V. 2001. Mycobacterium tuberculosis signal transduction system required for persistent infections. Proc. Natl. Acad. Sci. USA 98:12706-11
201. Perez E, Samper S, Bordas Y, Guilhot C, Gicquel B, et al. 2001. An essential role for phoP in Mycobacterium tuberculosis virulence. Mol. Microbiol. 41:179-87
202. Parish T, Smith DA, Roberts G, Betts J, Stoker NG. 2003. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology 149:1423-35
203. Rickman L, Saldanha JW, Hunt DM, Hoar DN, Colston MJ, et al. 2004. A two-component signal transduction system with a PAS domain-containing sensor is required for virulence of Mycobacterium tuberculosis in mice. Biochem. Biophys. Res. Commun. 314:259-67
204. Dasgupta N, Kapur V, Singh KK, Das TK, Sachdeva S, et al. 2000. Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis. Tuber. Lung Dis. 80:141-59
205. Malhotra V, Sharma D, Ramanathan VD, Shakila H, Saini DK, et al. 2004. Disruption of response regulator gene, devR, leads to attenuation in virulence of Mycobacterium tuberculosis. FEMS Microbiol. Lett. 231:237-45
206. Slayden RA, Lee RE, Armour JW, Cooper AM, Orme IM, et al. 1996. Antimycobacterial action of thiolactomycin: an inhibitor of fatty acid and mycolic acid synthesis. Antimicrob. Agents Chemother. 40:2813-19
207. Kremer L, Douglas JD, Baulard AR, Morehouse C, Guy MR, et al. 2000. Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis. J. Biol. Chem. 275:16857-64
208. Douglas JD, Senior SJ, Morehouse C, Phetsukiri B, Campbell IB, et al. 2002. Analogues of thiolactomycin: potential drugs with enhanced anti-mycobacterial activity. Microbiology 148:3101-9
209. Kremer L, Dover LG, Carrere S, Nampoothiri KM, Lesjean S, et al. 2002. Mycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis. Biochem. J. 364:423-30
210. Parrish NM, Kuhajda FP, Heine HS, Bishai WR, Dick JD. 1999. Antimycobacterial activity of cerulenin and its effects on lipid biosynthesis. J. Antimicrob. Chemother. 43:219-26
211. Parrish NM, Houston T, Jones PB, Townsend C, Dick JD. 2001. In vitro activity of a novel antimycobacterial compound, N-octanesulfonylacetamide, and its effects on lipid and mycolic acid synthesis. Antimicrob. Agents Chemother. 45:1143-50
212. Mitchison D. 2004. The search for new sterilizing anti-tuberculosis drugs. Front. Biosci. 9:1059-72
213. Zhang Y, Zhang H, Sun Z. 2003. Susceptibility of Mycobacterium tuberculosis to weak acids. J. Antimicrob. Chemother. 52:56-60
214. Deretic V, Philipp W, Dhandayuthapani S, Mudd MH, Curcic R, et al. 1995. Mycobacterium tuberculosis is a natural mutant with an inactivated oxidative stress regulatory gene: implications for sensitivity to isoniazid. Mol. Microbiol. 17:889-900
215. Sherman DR, Sabo PJ, Mickey MJ, Arain TM, Mahairas GG, et al. 1995. Disparate responses to oxidative stress in saprophytic and pathogenic mycobacteria. Proc. Natl. Acad. Sci. USA 92:6625-29
216. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, et al. 1995. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269:496-512
217. Dougherty TJ, Barrett JF, Pucci MJ. 2002. Microbial genomics and novel antibiotic discovery: new technology to search for new drugs. Curr. Pharm. Des. 8:1119-35
218. Chalker AF, Lunsford RD. 2002. Rational identification of new antibacterial drug targets that are essential for viability using a genomics-based approach. Pharmacol. Ther. 95:1-20
219. Volker C, Brown JR. 2002. Bioinformatics and the discovery of novel antimicrobial targets. Curr. Drug Targets Infect. Disord. 2:279-90
220. Haney SA, Alksne LE, Dunman PM, Murphy E, Projan SJ. 2002. Genomics in anti-infective drug discovery-getting to endgame. Curr. Pharm. Des. 8:1099-118
221. Cole S. 2002. Comparative mycobacterial genomics as a tool for drug target and antigen discovery. Eur. Respir. J. 36(Suppl.):78s-86
222. Schena M, Shalon D, Davis RW, Brown PO. 1995. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270:467-70
223. Hensel M, Shea JE, Gleeson C, Jones MD, Dalton E, et al. 1995. Simultaneous identification of bacterial virulence genes by negative selection. Science 269: 400-3
224. Balasubramanian V, Pavelka MS Jr, Bardarov SS, Martin J, Weisbrod TR, et al. 1996. Allelic exchange in Mycobacterium tuberculosis with long linear recombination substrates. J. Bacteriol. 178:273-79
225. Wilson M, DeRisi J, Kristensen HH, Imboden P, Rane S, et al. 1999. Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization. Proc. Natl. Acad. Sci. USA 96:12833-38
226. Betts JC, McLaren A, Lennon MG, Kelly FM, Lukey PT, et al. 2003. Signature gene expression profiles discriminate between isoniazid-, thiolactomycin-, and triclosan-treated Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 47:2903-13
227. Betts JC, Lukey PT, Robb LC, McAdam RA, Duncan K. 2002. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol. 43:717-31
228. Goulding CW, Apostol M, Anderson DH, Gill HS, Smith CV, et al. 2002. The TB structural genomics consortium: providing a structural foundation for drug discovery. Curr. Drug Targets Infect. Disord. 2:121-41
229. Crabb C. 2002. A new TB drug by 2010- or sooner? Bull. World Health Organ. 80:518-19
230. Orme I, Tuberculosis Drug Screening Program. 2001. Search for new drugs for treatment of tuberculosis. Antimicrob. Agents Chemother. 45:1943-46
231. Lee RE, Protopopova M, Crooks E, Slayden RA, Terrot M, et al. 2003. Combinatorial lead optimization of [1,2]-diamines based on ethambutol as potential antituberculosis preclinical candidates. J. Comb. Chem. 5:172-87
232. Changsen C, Franzblau SG, Palittapongarnpim P. 2003. Improved green fluorescent protein reporter gene-based microplate screening for antituberculosis compounds by utilizing an acetamidase promoter. Antimicrob. Agents Chemother. 47:3682-87
233. Projan S. 2002. New (and not so new) antibacterial targets-from where and when will the novel drugs come? Curr. Opin. Pharmacol. 2:513-22
234. Projan S. 2003. Why is big Pharma getting out of antibacterial drug discovery? Curr. Opin. Microbiol. 6:427-30
235. McDermott W. 1958. Microbial persistence. Yale J. Biol. Med. 30:257-91