Previous Article | Next Article 
Antimicrob Agents Chemother. 1994 September; 38(9): 2054-2058
Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis.
L G Wayne and
H A Sramek
Tuberculosis Research Laboratory, U.S. Department of Veterans Affairs Medical Center, Long Beach, California 90822.
ABSTRACT
Very abrupt exposure to anaerobic conditions has a lethal effect on actively growing cultures of Mycobacterium tuberculosis. However, incubation under conditions in which oxygen is depleted gradually causes M. tuberculosis to shift down from active replication to dormancy. The dormant bacilli are resistant to the bactericidal effects of anaerobiosis and also exhibit partial or complete resistance to the bactericidal effects of isoniazid and rifampin. On the other hand, metronidazole, a drug specific for anaerobes, kills dormant tubercle bacilli under anaerobic conditions, but it has no effect on actively growing aerobic cultures. The lethal effect of metronidazole under anaerobic conditions is enhanced by rifampin. The possible implications of these findings on the phenomenon of latency in tuberculosis are discussed.
Antimicrob Agents Chemother. 1994 September; 38(9): 2054-2058
This article has been cited by other articles:
-
Mukamolova, G. V., Turapov, O., Malkin, J., Woltmann, G., Barer, M. R.
(2010). Resuscitation-promoting Factors Reveal an Occult Population of Tubercle Bacilli in Sputum. Am. J. Respir. Crit. Care Med.
181: 174-180
[Abstract]
[Full Text]
-
Ginsberg, A. M., Laurenzi, M. W., Rouse, D. J., Whitney, K. D., Spigelman, M. K.
(2009). Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects. Antimicrob. Agents Chemother.
53: 3720-3725
[Abstract]
[Full Text]
-
Hoff, D. R., Caraway, M. L., Brooks, E. J., Driver, E. R., Ryan, G. J., Peloquin, C. A., Orme, I. M., Basaraba, R. J., Lenaerts, A. J.
(2008). Metronidazole Lacks Antibacterial Activity in Guinea Pigs Infected with Mycobacterium tuberculosis. Antimicrob. Agents Chemother.
52: 4137-4140
[Abstract]
[Full Text]
-
Via, L. E., Lin, P. L., Ray, S. M., Carrillo, J., Allen, S. S., Eum, S. Y., Taylor, K., Klein, E., Manjunatha, U., Gonzales, J., Lee, E. G., Park, S. K., Raleigh, J. A., Cho, S. N., McMurray, D. N., Flynn, J. L., Barry, C. E. III
(2008). Tuberculous Granulomas Are Hypoxic in Guinea Pigs, Rabbits, and Nonhuman Primates. Infect. Immun.
76: 2333-2340
[Abstract]
[Full Text]
-
Karakousis, P. C., Williams, E. P., Bishai, W. R.
(2008). Altered expression of isoniazid-regulated genes in drug-treated dormant Mycobacterium tuberculosis. J Antimicrob Chemother
61: 323-331
[Abstract]
[Full Text]
-
Taneja, N. K., Tyagi, J. S.
(2007). 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
60: 288-293
[Abstract]
[Full Text]
-
Williams, E. P., Lee, J.-H., Bishai, W. R., Colantuoni, C., Karakousis, P. C.
(2007). Mycobacterium tuberculosis SigF Regulates Genes Encoding Cell Wall-Associated Proteins and Directly Regulates the Transcriptional Regulatory Gene phoY1. J. Bacteriol.
189: 4234-4242
[Abstract]
[Full Text]
-
Cho, S. H., Warit, S., Wan, B., Hwang, C. H., Pauli, G. F., Franzblau, S. G.
(2007). Low-Oxygen-Recovery Assay for High-Throughput Screening of Compounds against Nonreplicating Mycobacterium tuberculosis. Antimicrob. Agents Chemother.
51: 1380-1385
[Abstract]
[Full Text]
-
Iona, E., Giannoni, F., Pardini, M., Brunori, L., Orefici, G., Fattorini, L.
(2007). Metronidazole plus Rifampin Sterilizes Long-Term Dormant Mycobacterium tuberculosis. Antimicrob. Agents Chemother.
51: 1537-1540
[Abstract]
[Full Text]
-
Borody, T J, Heifets, L B
(2006). Severe recurrent Crohn's disease of ileocolonic anastomosis and antimicrobial (anti-mycobacterial) therapy.. Gut
55: 1211-1211
[Full Text]
-
Warner, D. F., Mizrahi, V.
(2006). Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy. Clin. Microbiol. Rev.
19: 558-570
[Abstract]
[Full Text]
-
Manjunatha, U. H., Boshoff, H., Dowd, C. S., Zhang, L., Albert, T. J., Norton, J. E., Daniels, L., Dick, T., Pang, S. S., Barry, C. E. III
(2006). Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA
103: 431-436
[Abstract]
[Full Text]
-
Smith, I., Nathan, C., Peavy, H. H.
(2005). Progress and New Directions in Genetics of Tuberculosis: An NHLBI Working Group Report. Am. J. Respir. Crit. Care Med.
172: 1491-1496
[Abstract]
[Full Text]
-
Cardona, P-J., Ruiz-Manzano, J.
(2004). On the nature of Mycobacterium tuberculosis-latent bacilli. Eur Respir J
24: 1044-1051
[Abstract]
[Full Text]
-
Starck, J., Kallenius, G., Marklund, B.-I., Andersson, D. I., Akerlund, T.
(2004). Comparative proteome analysis of Mycobacterium tuberculosis grown under aerobic and anaerobic conditions. Microbiology
150: 3821-3829
[Abstract]
[Full Text]
-
Timmins, G. S., Master, S., Rusnak, F., Deretic, V.
(2004). Requirements for Nitric Oxide Generation from Isoniazid Activation In Vitro and Inhibition of Mycobacterial Respiration In Vivo. J. Bacteriol.
186: 5427-5431
[Abstract]
[Full Text]
-
Whittington, R. J., Marshall, D. J., Nicholls, P. J., Marsh, I. B., Reddacliff, L. A.
(2004). Survival and Dormancy of Mycobacterium avium subsp. paratuberculosis in the Environment. Appl. Environ. Microbiol.
70: 2989-3004
[Abstract]
[Full Text]
-
Nuermberger, E. L., Yoshimatsu, T., Tyagi, S., Bishai, W. R., Grosset, J. H.
(2004). Paucibacillary Tuberculosis in Mice after Prior Aerosol Immunization with Mycobacterium bovis BCG. Infect. Immun.
72: 1065-1071
[Abstract]
[Full Text]
-
Barrow, E. W., Westbrook, L., Bansal, N., Suling, W. J., Maddry, J. A., Parker, W. B., Barrow, W. W.
(2003). Antimycobacterial activity of 2-methyl-adenosine. J Antimicrob Chemother
52: 801-808
[Abstract]
[Full Text]
-
Florczyk, M. A., McCue, L. A., Purkayastha, A., Currenti, E., Wolin, M. J., McDonough, K. A.
(2003). A Family of acr-Coregulated Mycobacterium tuberculosis Genes Shares a Common DNA Motif and Requires Rv3133c (dosR or devR) for Expression. Infect. Immun.
71: 5332-5343
[Abstract]
[Full Text]
-
Smith, I.
(2003). Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence. Clin. Microbiol. Rev.
16: 463-496
[Abstract]
[Full Text]
-
Haile, Y., Bjune, G., Wiker, H. G.
(2002). Expression of the mceA, esat-6 and hspX genes in Mycobacterium tuberculosis and their responses to aerobic conditions and to restricted oxygen supply. Microbiology
148: 3881-3886
[Abstract]
[Full Text]
-
Shleeva, M. O., Bagramyan, K., Telkov, M. V., Mukamolova, G. V., Young, M., Kell, D. B., Kaprelyants, A. S.
(2002). Formation and resuscitation of 'non-culturable' cells of Rhodococcus rhodochrous and Mycobacterium tuberculosis in prolonged stationary phase. Microbiology
148: 1581-1591
[Abstract]
[Full Text]
-
Purkayastha, A., McCue, L. A., McDonough, K. A.
(2002). Identification of a Mycobacterium tuberculosis Putative Classical Nitroreductase Gene Whose Expression Is Coregulated with That of the acr Gene within Macrophages, in Standing versus Shaking Cultures, and under Low Oxygen Conditions. Infect. Immun.
70: 1518-1529
[Abstract]
[Full Text]
-
Florczyk, M. A., McCue, L. A., Stack, R. F., Hauer, C. R., McDonough, K. A.
(2001). Identification and Characterization of Mycobacterial Proteins Differentially Expressed under Standing and Shaking Culture Conditions, Including Rv2623 from a Novel Class of Putative ATP-Binding Proteins. Infect. Immun.
69: 5777-5785
[Abstract]
[Full Text]
-
Peh, H. L., Toh, A., Murugasu-Oei, B., Dick, T.
(2001). In Vitro Activities of Mitomycin C against Growing and Hypoxic Dormant Tubercle Bacilli. Antimicrob. Agents Chemother.
45: 2403-2404
[Full Text]
-
Flynn, J. L., Chan, J.
(2001). Tuberculosis: Latency and Reactivation. Infect. Immun.
69: 4195-4201
[Full Text]
-
Sander, P., Papavinasasundaram, K. G., Dick, T., Stavropoulos, E., Ellrott, K., Springer, B., Colston, M. J., Bottger, E. C.
(2001). Mycobacterium bovis BCG recA Deletion Mutant Shows Increased Susceptibility to DNA-Damaging Agents but Wild-Type Survival in a Mouse Infection Model. Infect. Immun.
69: 3562-3568
[Abstract]
[Full Text]
-
Boon, C., Li, R., Qi, R., Dick, T.
(2001). Proteins of Mycobacterium bovis BCG Induced in the Wayne Dormancy Model. J. Bacteriol.
183: 2672-2676
[Abstract]
[Full Text]
-
Murugasu-Oei, B., Dick, T.
(2000). Bactericidal activity of nitrofurans against growing and dormant Mycobacterium bovis BCG. J Antimicrob Chemother
46: 917-919
[Abstract]
[Full Text]
-
Hu, Y., Mangan, J. A., Dhillon, J., Sole, K. M., Mitchison, D. A., Butcher, P. D., Coates, A. R. M.
(2000). Detection of mRNA Transcripts and Active Transcription in Persistent Mycobacterium tuberculosis Induced by Exposure to Rifampin or Pyrazinamide. J. Bacteriol.
182: 6358-6365
[Abstract]
[Full Text]
-
Primm, T. P., Andersen, S. J., Mizrahi, V., Avarbock, D., Rubin, H., Barry, C. E. III
(2000). The Stringent Response of Mycobacterium tuberculosis Is Required for Long-Term Survival. J. Bacteriol.
182: 4889-4898
[Abstract]
[Full Text]
-
Lauzardo, M., Ashkin, D.
(2000). Phthisiology at the Dawn of the New Century. Chest
117: 1455-1473
[Abstract]
[Full Text]
-
Mulder, M. A., Zappe, H., Steyn, L. M.
(1999). The Mycobacterium tuberculosis katG promoter region contains a novel upstream activator. Microbiology
145: 2507-2518
[Abstract]
[Full Text]
-
Samuelson, J.
(1999). Why Metronidazole Is Active against both Bacteria and Parasites. Antimicrob. Agents Chemother.
43: 1533-1541
[Full Text]
-
Brooks, J. V., Furney, S. K., Orme, I. M.
(1999). Metronidazole Therapy in Mice Infected with Tuberculosis. Antimicrob. Agents Chemother.
43: 1285-1288
[Abstract]
[Full Text]
-
Lim, A., Eleuterio, M., Hutter, B., Murugasu-Oei, B., Dick, T.
(1999). Oxygen Depletion-Induced Dormancy in Mycobacterium bovis BCG. J. Bacteriol.
181: 2252-2256
[Abstract]
[Full Text]
-
Michele, T. M., Ko, C., Bishai, W. R.
(1999). Exposure to Antibiotics Induces Expression of the Mycobacterium tuberculosis sigF Gene: Implications for Chemotherapy against Mycobacterial Persistors. Antimicrob. Agents Chemother.
43: 218-225
[Abstract]
[Full Text]
-
Deidda, D., Lampis, G., Fioravanti, R., Biava, M., Porretta, G. C., Zanetti, S., Pompei, R.
(1998). Bactericidal Activities of the Pyrrole Derivative BM212 against Multidrug-Resistant and Intramacrophagic Mycobacterium tuberculosis Strains. Antimicrob. Agents Chemother.
42: 3035-3037
[Abstract]
[Full Text]
-
Yuan, Y., Crane, D. D., Simpson, R. M., Zhu, Y., Hickey, M. J., Sherman, D. R., Barry, C. E. III
(1998). The 16-kDa alpha -crystallin (Acr) protein of Mycobacterium tuberculosis is required for growth in macrophages. Proc. Natl. Acad. Sci. USA
95: 9578-9583
[Abstract]
[Full Text]
-
Cunningham, A. F., Spreadbury, C. L.
(1998). Mycobacterial Stationary Phase Induced by Low Oxygen Tension: Cell Wall Thickening and Localization of the 16-Kilodalton alpha -Crystallin Homolog. J. Bacteriol.
180: 801-808
[Abstract]
[Full Text]