Metronidazole Lacks Activity against Mycobacterium tuberculosis in an In Vivo Hypoxic Granuloma Model of Latency

G.^Klinkenberg, Lee; A.^Sutherland, Lesley; R.^Bishai, William; C.^Karakousis, Petros
July 2008
Journal of Infectious Diseases;7/15/2008, Vol. 198 Issue 2, p275
Academic Journal
During human latent tuberculosis (TB) infection, dormant bacilli putatively reside within the hypoxic environment of caseating lung granulomas. The anaerobic drug metronidazole has antituberculous activity under hypoxic conditions in vitro but lacks activity against murine TB. In the present study, we used the hypoxia marker pimonidazole to demonstrate the presence of hypoxia in a novel in vivo granuloma model of Mycobacterium tuberculosis latency. We also used a high-throughput, microarray-based technique to identify mycobacterial genes essential to hypoxia and showed that this in vivo model correctly identified 51% of hypoxia-attenuated mutants, a significantly larger percentage than that identified by the mouse (29%) and guinea pig (29%) aerosol models of TB. Although isoniazid showed activity during the first 28 days of therapy and rifampin was active against dormant bacilli after the establishment of hypoxia, metronidazole showed no antituberculous activity in this in vivo hypoxic granuloma model of M. tuberculosis dormancy.


Related Articles

  • Isolation and Identification of Mycobacterium from Extrapulmonary Specimen at NTRL, NIDCH. Mostofa Kamal, S. M.; Ahasan, Ham Nazmul; Ahmed, Sharmin; Ayaz, Kfm; Mahbub, Md. Shahriar; Imran Khan, Mohammad Ashik; Gupta, Ratan Das; Alam, Md. Billal; Miah, Md. Titu // Journal of Medicine;Jul2010, Vol. 11 Issue 2, p128 

    Objective of the study was to see the frequency of isolation of Mycobacterium among different extrapulmonary specimens. The study was carried out at NTRL (National Tuberculosis reference laboratory), NIDCH Bangladesh during January 2008-June 2009. This study was carried out retrospectively by...

  • Drug susceptibility test of Mycobacterium tuberculosis by nitrate reductase assay. Ani, Agatha E.; Dalyop, Y. B.; Agbaji, O.; Idoko, J. // Journal of Infection in Developing Countries;2009, Vol. 3 Issue 1, p16 

    Background: Drug susceptibility testing for Mycobacterium tuberculosis (M. tuberculosis) is especially required in difficult cases of tuberculosis (TB) chemotherapy and in cases of multidrug resistance (MDR-TB; combined resistance to isonizid and rifampicin with or without resistance to any...

  • Targeted Drug-Resistance Testing Strategy for Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005-2008. Velásquez, Gustavo E.; Yagui, Martin; Cegielski, J. Peter; Asencios, Luis; Bayona, Jaime; Bonilla, Cesar; Jave, Hector O.; Yale, Gloria; Suárez, Carmen; Atwood, Sidney; Contreras, Carmen C.; Shin, Sonya S. // Emerging Infectious Diseases;Mar2011, Vol. 17 Issue 3, p432 

    The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005-November 2008 were...

  • Mycobacterium tuberculosis Beijing Genotype, the Netherlands. Borgdorff, Martien W.; de Haas, Petra; Kremer, Kristin; van Soolingen, Dick // Emerging Infectious Diseases;Oct2003, Vol. 9 Issue 10, p1310 

    To determine whether the Beijing genotype of Mycobacterium tuberculosis is emerging in the Netherlands, we collected data on 6,829 patients during 1993 to 2000. Six percent had the Beijing genotype. This genotype was associated with diagnosis in recent years, young age, nationality, and...

  • Elevated ex vivo monocyte chemotactic protein-1 (CCL2) in pulmonary as compared with extra-pulmonary tuberculosis. Hasan, Zahra; Zaidi, Irfan; Jamil, Bushra; M Aslam Khan; Akbar Kanji; and Rabia Hussain // BMC Immunology;2005, Vol. 6, p1 

    Background: Tuberculosis causes 3 million deaths annually. The most common site of tuberculosis is pulmonary however; extra-pulmonary forms of the disease also remain prevalent. Restriction of Mycobacterium tuberculosis depends on effective recruitment and subsequent activation of T lymphocytes,...

  • Mycobacterium tuberculosis Transcriptional Adaptation, Growth Arrest and Dormancy Phenotype Development Is Triggered by Vitamin C. Taneja, Neetu Kumra; Dhingra, Sakshi; Mittal, Aditya; Naresh, Mohit; Tyagi, Jaya Sivaswami // PLoS ONE;2010, Vol. 5 Issue 5, p1 

    Background: Tubercle bacilli are thought to persist in a dormant state during latent tuberculosis (TB) infection. Although little is known about the host factors that induce and maintain Mycobacterium tuberculosis (M. tb) within latent lesions, O2 depletion, nutrient limitation and acidification...

  • Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence. Peyron, Pascale; Vaubourgeix, Julien; Poquet, Yannick; Levillain, Florence; Botanch, Catherine; Bardou, Fabienne; Daffé, Mamadou; Emile, Jean-François; Marchou, Bruno; Cardona, Pere-Joan; de Chastellier, Chantal; Altare, Frédéric // PLoS Pathogens;Nov2008, Vol. 4 Issue 11, p1 

    Tuberculosis (TB) is characterized by a tight interplay between Mycobacterium tuberculosis and host cells within granulomas. These cellular aggregates restrict bacterial spreading, but do not kill all the bacilli, which can persist for years. In-depth investigation of M. tuberculosis...

  • Mycobacterium tuberculosis Genotype and Case Notification Rates, Rural Vietnam, 2003-2006. Tran N. Buu; Mai N.T. Huyen; Nguyen N.T. Lan; Hoang T. Quy; Nguyen V. Hen; Zignol, Matteo; Borgdorff, Martien W.; Van Soolingen, Dick; Cobelens, Frank G. J. // Emerging Infectious Diseases;Oct2009, Vol. 15 Issue 10, p1570 

    Tuberculosis case notification rates (CNRs) for young adults in Vietnam are increasing. To determine whether this finding could reflect emergence of Mycobacterium tuberculosis Beijing genotype, we studied all new sputum smear- positive pulmonary tuberculosis patients registered for treatment in...

  • Koch's bacillus. Peters, Michael // BMA A-Z Family Medical Encyclopedia;2004, p454 

    A definition of the term "Koch's bacillus" is presented. Also known as mycobacterium tuberculosis, the term refers to the microorganism that causes tuberculosis.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics