Victor J. DiRita
Genetic and Molecular Studies of Host-Microbe interactions
My research interests include understanding molecular biology of bacterial pathogens and the mechanisms by which they interact with hosts. Two microbes under investigation are Vibrio cholerae, agent of human cholera, and Campylobacter jejuni, a prevalent foodborne pathogen that causes gastroenteritis and diarrhea. Projects concerning V. cholerae include understanding the regulatory pathway that controls the two major pathogenicity determinants of the microbe, the cholera toxin and the toxin-coregulated pilus. We study regulatory proteins that work in concert to control expression of these two factors and thereby control the virulence of the microbe. We are also investigating the determinants for recognition and uptake of V. cholerae by intestinal M cells, a key aspect of the early immune response against this pathogen.
With Campylobacter jejuni, we are studying basic mechanisms underlying its biology and pathogenicity. C. jejuni is a common inhabitant of the intestinal tract of chickens, which are therefore an important reservoir of human infection. We developed many tools for genetic analysis in this pathogen, and we have applied those tools to study key traits of C. jejuni. In a screen for mutants defective in chick colonization we identified genes encoding a system of protein glycosylation, and regulatory genes that may control the levels of important second messenger signals in the microbe during host colonization. We have also identified a number of genes required for natural transformation, the process by which bacteria take up their own DNA from the outside of the cell. Genes required for transformation in C. jejuni share similarity to genes in other microbes involved in a variety of processes including both DNA uptake and protein secretion. Our interest is to uncover the role of natural transformation in generating strain diversity in C. jejuni.
Blanco, L.P and DiRita, V.J. (2006) Bacterial-associated cholera toxin and GM1 binding are required for transcytosis of classical biotype Vibrio cholerae through an in vitro M cell model system. Cell. Microbiol. 8:982-998.
Withey, J.H. and DiRita, V.J. (2006) The toxbox: Specific DNA sequence requirements for activation of Vibrio cholerae virulence genes by ToxT. Mol. Microbiol. 59:1779-1789.
Kakuda, T. and DiRita, V.J. (2006) Cj1496c encodes a Campylobacter jejuni glycoprotein that influences invasion of human epithelial cells and colonization of the chick gastrointestinal tract. Infect.Immun. 74:4715-4723.
Blanco, L.P. and DiRita, VJ (2006) Antibodies enhance interaction of Vibrio cholerae with intestinal M-like cells. Infect. Immun. 74: 6957-6451.
Elliott, K.T. and DiRita, V.J. (2008) Characterization of CetA and CetB, a bipartite energy taxis system in Campylobacter jejuni. Mol. Microbiol. 69:1091-1103.
Young, K.T., Davis, L., and DiRita, V.J. (2007) Campylobacter jejuni: Molecular Biology and Pathogenesis. Nat. Rev. Micro. 5: 665-679.
Matson, J.S., Withey, J.H and DiRita, V.J. (2007) Regulatory Networks Controlling Vibrio cholerae Virulence Gene Expression. Infect Immun. 2007 75:5542-5549.