Murine model to study the invasion and survival of Mycobacterium tuberculosis in the central nervous system

Nicholas A. Be, Gyanu Lamichhane, Jacques Grosset, Sandeep Tyagi, Qi Jian Cheng, Kwang Sik Kim, William R. Bishai, Sanjay K. Jain

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


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.

Original languageEnglish
Pages (from-to)1520-1528
Number of pages9
JournalJournal of Infectious Diseases
Issue number10
StatePublished - 15 Nov 2008
Externally publishedYes


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