Martin I. Voskuil

Assistant Professor Ph.D., Univ. of Wisconsin, Madison

Current Research

Dr. Voskuil joined the Department of Microbiology in March 2003 to investigate the dormant state of Mycobacterium tuberculosis during latent infection. M. tuberculosis remains the leading bacterial cause of global mortality. A primary reason for the continued threat from M. tuberculosis lies in its ability to establish an asymptomatic latent infection, which serves as a reservoir for future infections. One-third of the world's population is latently infected with tuberculosis and current treatment of latent infections is inefficient. The low metabolic activity of latent bacilli appears to confer resistance to existing antimicrobials, making global eradication of M. tuberculosis unrealistic.

Little is known about the nature of the latent state, or the host factors that prevent active disease. Control of bacterial replication in animal models of latency requires a functional immune system including production of IFN, TNF and nitric oxide (NO). In vitro studies demonstrate M. tuberculosis has the ability to undergo a distinct physiologic adaptation to a dormant state in response to falling O2 levels. This hypoxia-induced dormant state is marked by bacteriostasis, in addition to metabolic, chromosomal, and structural changes in the bacteria. Both NO and hypoxia instigate a rapid and dramatic induction of a set of 48 genes (dormancy regulon) in M. tuberculosis. These genes are coordinately regulated and encode functions that are essential for survival in a dormant state. NO and O2 levels modulate the induction of the dormancy regulon and concurrently control bacterial respiration and growth. Cytochrome oxidase, the terminal enzyme in electron transport, likely plays a central role as the target of reversible NO respiratory inhibition and the sensor and integrator of NO and O2 levels. It appears that control of respiration by NO production or O2 deprivation via granuloma formation is a potent mechanism for immune control of M. tuberculosis. However, the bacilli have evolved mechanisms to survive and persist during the growth arresting state produced by active immune pressure. Research in Dr. Voskuil's laboratory utilizes genetic, microarray, biochemical, and animal studies to investigate the mechanisms employed by M. tuberculosis to survive during latent disease, with a particular focus on the role of the genes in the dormancy regulon.

Recent Publications

Click Here For More Of Dr. Voskuil's Publications

Roback P, Beard J, Baumann D, Gille C, Henry K, Krohn S, Wiste H, Voskuil MI, Rainville C, Rutherford R. A predicted operon map for Mycobacterium tuberculosis. Nucleic Acids Res. 2007 Jul 25; [Epub ahead of print]

Lin MY, Geluk A, Smith SG, Stewart AL, Friggen AH, Franken KL, Verduyn MJ, van Meijgaarden KE, Voskuil MI, Dockrell HM, Huygen K, Ottenhoff TH, Klein MR. Lack of immune responses to Mycobacterium tuberculosis DosR regulon proteins following Mycobacterium bovis BCG vaccination. Infect Immun. 2007 Jul;75(7):3523-30.

Voskuil, M. I., K. Visconti, & G. K. Schoolnik. 2004. Mycobacterium tuberculosis gene expression during adaptation to stationary phase and low-oxygen dormancy. Tuberculosis. 84:218-227.

Voskuil, M. I. 2004. Commentary: Mycobacterium tuberculosis gene expression during environmental conditions associated with latency. Tuberculosis. 84:138-143.

Schnappinger, D., S. Ehrt, M. I. Voskuil, Y. Liu, J. A. Mangan, I. M. Monahan, G. Dolganov, B. Efron, P. D. Butcher, C. Nathan, & G. K. Schoolnik. 2003. Transcriptional Adaptation of Mycobacterium tuberculosis Within Macrophages: Insights into the phagosomal environment and strategies for bacterial survival. J. Exp. Med. 198:693-704.

Voskuil, M. I., D. Schnappinger, M. Harrell, K. Visconti, G. Dolganov, D. R. Sherman, & G. K. Schoolnik. 2003. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J. Exp. Med. 198:705-13.

Rodriguez, G., M. I. Voskuil, B. Gold, G. K. Schoolnik, & 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. 70:3371-3381.

Park, H.-D., K. M. Guinn, M. I. Harrell, R. Liao, M. I. Voskuil, M. Tompa, G. K. Schoolnik & D. R. Sherman. 2003. Rv3133c/dosR is a transcription factor that mediates the hypoxic response of M. tuberculosis. Mol. Microbiol. 48:833-843.

Schnappinger, D., S. Ehrt, G. K. Schoolnik, & M. I. Voskuil. 2002. Genome-wide expression profiling of intracellular bacteria: the interaction of Mycobacterium tuberculosis with macrophages. In “Immunology of Infection”. 2nd ed. Eds S. H. E. Kaufman & D. Kabelitz. Methods Microbiol. pp.169-180.

Manganelli, R., M. I. Voskuil, G. K. Schoolnik, M. Gomez, & I. Smith. 2002. Role of the ECF sigma factor H in Mycobacterium tuberculosis global gene expression. Mol. Microbiol. 45:365-74.

Sherman, D. R., M. I. Voskuil, D. Schnappinger, R. Liao, M. I. Harrell, & G. K. Schoolnik. 2001. Alpha-crystalline and Adaptation to Hypoxia in Mycobacterium tuberculosis. Proc. Nat. Acad. Sci. USA. 98:7534-9.