Bradley D. Jones, Ph.D.
Ph.D., University of Maryland, 1989 |
Associate Professor of Microbiology BSL-3 Lab Director Campus address: 3-330A BSB Mailing address: 51 Newton Rd. 3-330A Bowen Science Building Iowa City, IA 52242 Phone: 319-353-5457 Email: |
Interactions Between Pathogenic Bacteria and Mammalian Cells
Pathogenic Salmonella species cause disease in a host by invading epithelial cells of the intestine and subsequently entering and growing within macrophages of the lymphatic system. Salmonella invasion of host cells is accompanied by dramatic changes of the host cell membrane that indicate that these bacteria activate existing cellular signal transduction pathways. The ability of Salmonella to invade host cells is tightly regulated by a number of environmental and genetic signals.
The Jones laboratory is working on several lines of research to understand the interaction of Salmonella with host cells. One project is aimed at understanding the regulatory mechanisms of Salmonella invasion. Recent work in our lab has identified several genes (hilE, hha, pag, and ams) that encode repressors of the invasion transcriptional activator, HilA. Work in progress has found that mutant strains lacking repressor genes constitutively express the invasive phenotype. However, constitutive expression of invasion appears to attenuate the virulence of the bacteria leading to the idea that the processes of activation and deactivation of virulence gene expression are equally important in Salmonella virulence. Work is in progress to characterize the effects of these mutations in detail. In addition, we are in the process of searching for inhibitory peptides of the regulators of Salmonella invasion in effort to develop therapeutics for the effects of Salmonella invasion.
Another project is aimed at understanding how Salmonella establishes colonization of a host intestinal surface (biofilm formation). Recent work from the lab indicates that both extracellular matrix components and adherence factors such as fimbriae play specific and important roles in establishing the extensive biofilm that we observe in the colonization of tissue culture cells and host intestinal tissue. GFP-labelled bacteria are being used to study these events by fluorescent confocal microscopy. Future goals of this work will be aimed at identifying genes involved in the formation of biofilm formation as well as identifying and studying in detail the cells that serve as the attachment sites of the bacteria. This work has many implications for understanding colonization of Salmonella in domestic animals such as chickens and pigs as well as the establishment of human disease.
Finally, a project is being developed with the Select Agent bacterium Francisella tularensis. This organism is of concern from a biodefense point of view. A transposition system has been developed for this organism so that various virulence properties of this organism can be mutated and studied. Several projects are currently being developed with this organism.
Additional Information
Recent publications
Buchan, B.W., R.L. McCaffrey, S.R. Lindemann, L.A. Allen, and B.D. Jones. 2009. Identification of migR, a regulatory element of the Francisella tularensis live vaccine strain iglABCD virulence operon required for normal replication and trafficking in macrophages. Infect Immun 77(6):2517-29.
Schulert, G.S., R.L. McCaffrey, B.W Buchan, S.R. Lindemann, C. Hollenback, and B.D. Jones. 2009. Francisella tularensis genes required for inhibition of the neutrophil respiratory burst and intramacrophage growth identified by random transposon mutagenesis of strain LVS. Infect Immun 77(4):1324-36.
Buchan, B.S., M.K. McLendon, and B.D. Jones. 2008. Identification of differentially regulated Francisella tularensis genes by use of a newly developed Tn5-based transposon delivery system. Appl Environ Microbiol 74(9):2637-45.
Lindemann, S.R., M.K. McLendon, M.A. Apicella, and B.D. Jones. 2007. An in vitro model system used to study adherence and invasion of Francisella tularensis live vaccine strain in nonphagocytic cells. Infect Immun 75(6):3178-82.