Jon Goguen, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Molecular Genetics and Microbiology

Other Affiliation(s):
   Bacterial Genetics and Pathogenesis
   Program in Immunology and Virology

Function and Regulation of Virulence Genes in the Plague Bacillus, Yersinia pestis

As is true for most pathogenic bacteria, and in particular the intracellular pathogens, the molecular basis of virulence in plague is poorly understood. In recent years we have identified a number of genes in Y. pestis that are essential to the disease process. We are currently conducting an integrated program of genetic, biochemical, and experimental infection studies to determine the functions of the products of these genes. Much of our recent work has concerned a gene we call pla, which produces a plasminogen activator, and plays an important role in dissemination of the bacteria through host tissues. Some of these virulence genes also show interesting patterns of expression, including induction on entry of the bacterium into macrophages of the host. Determining the mechanism of this regulation has also become an important focus of our laboratory.

Representative Publications

Yother, J., and J.D. Goguen (1985). Isolation and characterization of Ca2+-blind mutants of Yersinia pestis. J. Bacteriol. 164, 704-711.

Yother, J., and J.D. Goguen (1986). A temperature-controlled regulon associated with the low calcium response of Yersinia pestis. J. Bacteriol. 165, 443-447.

Goguen, J.D., W.S. Walker, T.P. Hatch, and J. Yother (1986). Plasmid encoded cytotoxicity in Yersinia pestis and Yersinia pseudotuberculosis. Infect. Immun. 51, 788-794.

Sodiende, O.A., and J.D. Goguen (1988). Genetic analysis of the 9.5 kilobase virulence plasmid of Yersinia pestis. Infect. Immun. 56, 2743-2748.

Sodiende, O.A., A.K. Sample, R.R. Brubaker, and J.D. Goguen (1988). The plasminogen activator/coagulase gene of Yersinia pestis is responsible for degredation of plasmid encoded outer membrane proteins. Infect. Immun. 56, 2749-2752.

Sodiende, O.A., and J.D. Goguen (1988). Nucleotide sequence of the plasminogen activator gene of Yersinia pestis: relationship to ompT of E. coli and gene E of Salmonella typhimurium. Infect. Immun. 57, 1517-1523.

Rotation Projects

Y. pestis can directly inject proteins into host cells that contact them. These proteins block many host cell functions, including the ability to produce pro-inflammatory cytokines. Our current model for the role of fibrin in aiding the inflammatory response to Y. pestis involves specific interactions between fibrin and neutrophils. By binding to fibrin, the neutrophils stop at a distance from the bacteria, permitting chemokine production. This ultimately surrounds the bacteria with inflammatory cells, containing them until specific immunity develops. One rotation project is designed to test this model: examine the course of infection in specific knockout mice that have neutrophils lacking proteins important in the fibrin interaction.

We have a developed a simple model for testing the ability of bacteria to block inflammatory cell accumulation in vivo. Another rotation project is to examine P. aeruginosa and appropriate P. aeruginosa protease mutants in this model, using specific knockout mice as appropriate.

Academic Background

PhD, UMass-Amherst, 1980

Keywords: Microbial Pathogenesis, Biochemistry, Infectious Disease

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