BACKGROUND: Tuberculosis of the central nervous system (CNS) is a serious, often fatal disease primarily affecting young children. It develops after hematogenous dissemination and subsequent invasion of the CNS by Mycobacterium tuberculosis. The microbial determinants involved in CNS disease are poorly characterized. METHODS: Hematogenously disseminated M. tuberculosis infection was simulated in BALB/c mice by intravenous challenge. Bacteria were recovered using standard culture techniques. Host immune response to M. tuberculosis infection was assessed by histopathological and cytokine profile analysis. By means of a pooled infection with genotypically defined M. tuberculosis mutants, bacterial genes required for invasion or survival were determined in the CNS and lung tissue. RESULTS: M. tuberculosis were detected in whole mouse brains as early as 1 day after intravenous infection and at all time points assessed thereafter. No significant immune response was elicited in the infected brain tissue, compared with extensive inflammation in the infected lung tissue at the same time point. We identified mutants for 5 M. tuberculosis genes (Rv0311, Rv0805, Rv0931c, Rv0986, and MT3280) with CNS-specific phenotypes, absent in lung tissue. CONCLUSIONS: We have identified CNS-specific M. tuberculosis genes involved in the pathogenesis of tuberculosis. Further characterization of these genes will help in understanding the microbial pathogenesis of CNS tuberculosis.
BACKGROUND:Tuberculosis of the central nervous system (CNS) is a serious, often fatal disease primarily affecting young children. It develops after hematogenous dissemination and subsequent invasion of the CNS by Mycobacterium tuberculosis. The microbial determinants involved in CNS disease are poorly characterized. METHODS: Hematogenously disseminated M. tuberculosis infection was simulated in BALB/c mice by intravenous challenge. Bacteria were recovered using standard culture techniques. Host immune response to M. tuberculosis infection was assessed by histopathological and cytokine profile analysis. By means of a pooled infection with genotypically defined M. tuberculosis mutants, bacterial genes required for invasion or survival were determined in the CNS and lung tissue. RESULTS:M. tuberculosis were detected in whole mouse brains as early as 1 day after intravenous infection and at all time points assessed thereafter. No significant immune response was elicited in the infected brain tissue, compared with extensive inflammation in the infected lung tissue at the same time point. We identified mutants for 5 M. tuberculosis genes (Rv0311, Rv0805, Rv0931c, Rv0986, and MT3280) with CNS-specific phenotypes, absent in lung tissue. CONCLUSIONS: We have identified CNS-specific M. tuberculosis genes involved in the pathogenesis of tuberculosis. Further characterization of these genes will help in understanding the microbial pathogenesis of CNS tuberculosis.
Authors: Nicholas A Be; Lee G Klinkenberg; William R Bishai; Petros C Karakousis; Sanjay K Jain Journal: Tuberculosis (Edinb) Date: 2011-08-09 Impact factor: 3.131
Authors: Samantha J Dando; Alan Mackay-Sim; Robert Norton; Bart J Currie; James A St John; Jenny A K Ekberg; Michael Batzloff; Glen C Ulett; Ifor R Beacham Journal: Clin Microbiol Rev Date: 2014-10 Impact factor: 26.132
Authors: Noton K Dutta; Smriti Mehra; Peter J Didier; Chad J Roy; Lara A Doyle; Xavier Alvarez; Marion Ratterree; Nicholas A Be; Gyanu Lamichhane; Sanjay K Jain; Michelle R Lacey; Andrew A Lackner; Deepak Kaushal Journal: J Infect Dis Date: 2010-06-01 Impact factor: 5.226
Authors: Elizabeth R Magden; Cristina M Weiner; Janet C Gilliland; Mary Ann DeGroote; Anne J Lenaerts; Lon V Kendall Journal: J Am Assoc Lab Anim Sci Date: 2011-03 Impact factor: 1.232