Faculty

Bacterial pathogenesis; Regulation of bacterial virulence in response to environmental cues.

     My research focuses on the ability of two bacterial pathogens to respond to environmental signals in order to induce the expression of virulence factors. One organism, Vibrio cholerae, utilizes two membrane-bound transcription factors, ToxR and TcpP, to initiate virulence gene expression. Both proteins harbor periplasmic domains with the potential to sense extracellular signals. Using random mutagenesis strategies we have identified domains of each protein that are involved in transcription activation and DNA binding as well as regions of protein-protein interaction between ToxR and TcpP.

     My other area of study is regulation of an adhesin known as pH 6 antigen in pathogenic Yersinia species. This is one of the few known adhesins that is functionally conserved between enteropathogenic Yersinia species and Yersinia pestis, the causative agent of Plague. We are currently studying the mechanism of environmental regulation of pH 6 antigen by a membrane-bound transcription factor PsaE. pH 6 antigen expression is tightly controlled, being expressed at pH 6 and 37 degrees C (body temperature). In addition to its regulation, we are also investigating the role of pH 6 antigen during experimental mouse infection and Yersinia's interaction with macrophages.

Selected Publications:

     Krukonis, E.S. & DiRita V.J.; (2003) DNA binding and ToxR responsiveness by the wing domain of TcpP, an activator of virulence gene expression in Vibrio cholerae, Mol. Cell, Vol. 12 (1) pp. 157-165.

     Crawford, J.A., Krukonis, E.S., DiRita, V.J. (2003) Membrane localization of the ToxR winged-helix domain is required for TcpP-mediated virulence gene activation in Vibrio cholerae; Mol. Micro., Vol 47 (5) pp. 1459-1473.

     Krukonis, E.S.; Yu, R.R.; & DiRita, V.J.; (2000) The Vibrio cholerae ToxR/TcpP/ToxT virulence cascade: distinct roles for two membrane-localized transcriptional activators on a single promoter; Mol. Micro., Vol 38 (1) pp. 67-84.

     Krukonis, E.S. & Isberg, R.R.; (2000) Integrin b -1 chain residues involved in substrate recognition and specificity of binding to invasin; Cell. Micro., Vol 2 (3) pp. 219-230.

     Krukonis, E.S.; Dersch, P.; Eble, J.A.; & Isberg, R.R.; (1998) Differential effects of integrin a -chain mutations on invasin and natural ligand interaction. JBC, Vol 273 (48) pp. 31837-31843.

    Krukonis, E.S. & Isberg, R.R.; (1998) SWIM analysis allows rapid identification of residues involved in invasin-mediated bacterial uptake. Gene, Vol 211 pp. 109-116.