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Dahl,
John
Mail
Research
Interests
The unifying theme of my laboratories research is to elucidate molecular mechanisms of bacterial dormancy. We work on two different bacterial systems: Mycobacterium and Myxococcus.
Mycobacterium tuberculosis
Tuberculosis is the leading cause of death world wide due to a single infectious agent. Upwards to a third of the world’s population is estimated to harbor latent M. tuberculosis infections although the vast majority of these people (~90%) will not develop tuberculosis in their lifetimes. About 5% of those infected are capable of developing active tuberculosis years after the initial infection and this often is a result of immunospression, which allows for spread of the infection. A vaccine exists for TB but is thought to have no value for adults. A multi-drug treatment exists although the cocktail of antibiotics must be taken for a minimum of six months; resulting in compliancy problems. Therefore urgency exists to better understand how M. tuberculosis adjusts its metabolism to survive within the host not only to develop improved vaccines but also faster-acting antibiotics. We study the stringent response of M. tuberculosis in effort to better understand how this global metabolic pathway allows this bacterium to remain viable in both long-term in vitro cultures and in mammalian hosts. The stringent response controls expression of a variety of different bacterial properties including DNA replication, cell shape, and production of known immunogens. In addition to the stringent response, we also study spontaneous mutations in M. tuberculosis that arise and are selected for during growth at low oxygen tensions. These mutations have enhance survival properties in vitro and may offer clues about how M. tuberculosis survives inside of the host.
Myxococcus xanthus
Myxococci are gram-negative, soil dwelling bacteria that are capable of existing in solitary vegetative-cell states when nutrients are plentiful. However, during nutrient starvation these bacteria participates in coordinated aggregation into cell mounds of upwards to 100,000 cells called fruiting bodies. After aggregation occurs cells are capable of morphogenesis into spores (myxospores) in a mechanism that is quite unique from gram-positive sporulation. These spores are capable of surviving in a dormant state for years before germinating back into vegetative cells. My laboratory studies protein components of the M. xanthus spore that are responsible for the ultrastructure of the spore and stress-resistant properties of the spore. We have identified a gene responsible for cortex biosynthesis in the spore and three genes, which code for major structural proteins in the spore. Inactivation of any of these four genes leads to alteration in fruiting body formation, sporulation, and/or stress resistance to heat, sonicaiton, lysozyme, SDS, and uv radiation. Completion of these studies will help understand a major property of bacteria: sporulation.
Publications
Olekhnovich, I.N., J.L. Dahl, and R.J. Kadner. 1999. Separate contributions of UhpA and CAP to activation of transcription of the uhpT promoter of Escherichia coli. J. Molec. Biol. 292: 973-986.
Wei, J., J.L. Dahl, J.W. Moulder, E.A. Roberts, P. O’Gaora, D. Young, and R.L. Friedman. 2000. Identification of a Mycobacterium tuberculosis gene that enhances mycobacterial survival in macrophages. J. Bacteriol. 182: 377-384.
Dahl, J.L., J. Wei, J.W. Moulder, S. Laal, and R.L. Friedman. 2001. Subcellular localization of the intracellular survival-enhancing Eis protein of Mycobacterium tuberculosis. Infect. & Immun. 69: 4295-4302.
Dahl, J.L. Kraus, C.N., Boshoff, H.I., Doan, B., Foley, K., Avarbock, D., Kaplan, G., Mizrahi, V., Rubin, H., Barry, C.E., 3rd. 2003. The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc. Natl. Acad. Sci. U S A. 100:10026-31.
Dahl, J.L. 2004. Electron microscopy analysis of Mycobacterium tuberculosis cell division. FEMS Microbiol Lett. 240:15-20.
Koo , H.C., Park, Y.H., Hamilton, M.J., Barrington, G.M., Davies, C.J., Kim, J.B., Dahl, J.L., Waters ,W.R., Davis, W.C. 2004. Analysis of the immune response to Mycobacterium avium subsp. paratuberculosis in experimentally infected calves. Infect Immun. 72:6870-83.
Dahl,J.L. Arora, K., Boshoff, H.I., Whiteford, D.C., Pacheco, S.A., Walsh, O.J., Lau-Bonilla, D., Davis, W.B., and Garza, A.G. 2005. Analysis of the Mycobacterium smegmatis Stringent Response. J. Bacteriol. 187: 2439-2447.
Dahl, J.L. 2005. Scanning Electron Microscopy Analysis of Aged Mycobacterium tuberculosis Cells. Can. J. Microbiol. 51:277-281.
Tengra, F.K., J.L. Dahl, D. Dutton, N.B. Caberoy, L. Coyne, and A.G. Garza. 2006. CbgA, a protein involved in cortex formation and stress resistance in Myxococcus xanthus spores. J. Bacteriol. In Press.
Samuel, L.P., C.-H. Song, J. Wei, E.A. Roberts, J.L. Dahl, C.E. Barry, III, E.-K. Jo, and R.L. Friedman. 2006. Expression, production, and release of the Eis protein by Mycobacterium tuberculosis during infection of macrophages and its effect on cytokine secretion. Microbiol. Accepted.
Dahl, J.L., F.K. Tengra, D. Dutton, J. Yan, T.M. Andacht, L. Coyne, and A.G. Garza. 2006. Identification of major sporulation proteins of Myxococcus xanthus using a proteomic approach. J. Bacteriol. Submitted. |
