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PROJECT M. TB
Yang Liu
Dirk Schnappinger
Martin I. Voskuil
Research focus: Current research is directed at understanding how Mycobacterium tuberculosis adapts to survive years of sequestration by the host immune system during the latent stage of infection. Whole genome DNA microarray analysis and classical genetic and biochemical techniques are being used to investigate the adaptive processes of M. tuberculosis to survival during nonreplicating persistence (NRP) and exposure to immune system anti-microbial factors (e.g. nitric oxide and reactive oxygen intermediates). The dramatic induction of a large set of genes (designated NRP genes) appears to link the natural adaptive process of M. tuberculosis for survival during conditions of nonreplicating persistence to the specific response of the bacilli to exposure to activated macrophages in a nitric oxide dependent manner.
Current collaborations: Dirk Schnappinger-Postdoctoral Fellow-Stanford University (M. tuberculosis gene expression in macrophages and microarray development), David Sherman-University of Washington-Seattle (transcriptional regulators for the adaptation to hypoxia), Issar Smith-Institute of Tuberculosis Research, NY (role of sigma factors and iron regulation in pathogenesis), Peter Small-Stanford University (microarray development and strain to strain mRNA profile comparisons), Clifton Berry III-NIH (ethambutol, mode of killing and improved drug design), and Alan Krensky-Stanford University (mechanism of killing by immune system anti-microbial protein, granulysin).
Supplementary data for publications
1. Manganelli, R., M. I. Voskuil, G. K. Schoolnik, M. Gomez, and I. Smith. 2002. Role of the extracytoplasmic-function sigma Factor sigmaH in Mycobacterium tuberculosis global gene expression. Mol. Microbiol. 45(2):365-74
TABLE 1: Genes induced in H37Rv by diamide
TABLE 2: Genes repressed in H37Rv by diamide
TABLE 3: Genes induced in sigH mutant by diamide
TABLE 4: Genes repressed in sigH mutant by diamide
2. Rodriguez, G., M. I. Voskuil, B. Gold, G. K. Schoolnik, and I. Smith. 2002. IdeR, an essential gene in Mycobacterium tuberculosis: Role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 70(7):3371-81.
TABLE 1: Genes induced in H37Rv by low iron
TABLE 2: Genes repressed in H37Rv by low iron
TABLE 3: Genes induced in ideR mutant compared to H37Rv
TABLE 4: Genes repressed in ideR mutant compared to H37Rv
TABLE 5: Genes induced in ideR complemented mutant compared to H37Rv
TABLE 6: Genes repressed in ideR complemented mutant compared to H37Rv
3. Manganelli, R., M. I. Voskuil, G. K. Schoolnik, and I. Smith. 2001. The Mycobacterium tuberculosis ECF sigma Factor sE: role in global gene expression and survival in macrophages. Mol. Microbiol. 41(2):423-37.
TABLE 1: Genes induced in H37Rv relative to sigma E mutant
TABLE 2: Genes repressed in H37Rv relative to sigma E mutant strain
TABLE 3: Genes induced in H37Rv after 90m SDS stress
TABLE 4: Genes repressed in H37Rv after 90m SDS stress
TABLE 5: Genes induced in sigma E mutant strain after 90m SDS stress
TABLE 6: Genes repressed in sigma E mutant strain after 90m SDS stress
4. Sherman, D. R., M. I. Voskuil, D. Schnappinger, R. Liao, M. I. Harrell, and G. K. Schoolnik. 2001. Alpha-crystalline and Adaptation to Hypoxia in Mycobacterium tuberculosis. Proc. Nat. Acad. Sci. USA. 98(13):7534-9.
TABLE 1: Hypoxia induced genes
TABLE 2: Hypoxia repressed genes