MECHANISMS AND REGULATION OF BACTERIAL VIRULENCE
My research focuses on two bacterial pathogens, Vibrio cholerae and Yersinia pestis.
V. cholerae, the causative agent of cholera, utilizes two membrane-bound transcription factors, ToxR and TcpP, to initiate virulence gene expression at the toxT promoter. 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. Current work aims to define the distinct roles of ToxR and TcpP in virulence gene activation. We are also interested in host factors that affect virulence gene expression during infection.
My other area of study is identification of adhesins of Y. pestis required for virulence. Y. pestis is the causative agent of plague. We are investigating the role of Ail, plasminogen activator, pH 6 antigen and other chaperone/usher systems that may affect virulence and/or the delivery of cytotoxic Yop proteins to host cells. Another objective is to understand the importance of adhesin redundancy during plague infection. A long-term goal of our work is to identify Y. pestis surface components that can serve as protective immunogens in vaccine formulations.
Yamashita, S., Lukacik, P., Barnard, T.J., Noinaj, N., Felek, S., Tsang, T.M., Krukonis, E.S., Hinnebusch, B.J., and Buchanan, S.K. 2011. Structural Insights into Ail-Mediated Adhesion in Yersinia pestis. Structure Vol. 19: 1672-1682.
Morgan, S.J., Felek, S., Gadwal, S., Koropatkin, N.M., Perry, W.J., Bryson, A.B., and Krukonis, E.S. 2011. The two faces of ToxR: activator of ompU, co-regulator of toxT in Vibrio cholerae. Mol Micro Vol. 81(1):113-128.
Felek, S., Jeong, J. J., Runco, L. M., Murray, S., Thanassi, D. and Krukonis, E. S. 2011. Contributions of chaperone/usher systems to cell binding, biofilm formation and Yersinia pestis virulence. Microbiology Vol. 157 (3):805-818. cover article
Goss, T. J., Seaborn, C. P., Gray, M. D. and Krukonis, E. S. 2010 Identification of the TcpP-binding site in the toxT promoter of Vibrio cholerae and the role of ToxR in TcpP-mediated activation. Infect Immun Vol. 78(10) pp. 4122-4133.
Felek, S., Tsang, T.M. and Krukonis, E.S. (2010) Three Yersinia pestis Adhesins Facilitate Yop Delivery to Eukaryotic Cells and Contribute to Plague Virulence. Infect Immun Vol. 78(10): pp. 4134-4150.
Tsang TM, Felek S, Krukonis ES 2010. Ail binding to fibronectin facilitates Yersinia pestis binding to host cells and Yop delivery. Infect Immun 78: 3358-3368.
Felek S, Muszynski A, Carlson RW, Tsang TM, Hinnebusch BJ, et al. 2010. Phosphoglucomutase of Yersinia pestis is required for autoaggregation and polymyxin B resistance. Infect Immun 78: 1163-1175.
Felek, S., and E. S. Krukonis. 2009. The Yersinia pestis Ail protein mediates binding and Yop delivery to host cells required for plague virulence. Infect Immun 77:825-836. cover article
Felek, S., M. B. Lawrenz, and E. S. Krukonis. 2008. The Yersinia pestis autotransporter YapC mediates host cell binding, autoaggregation and biofilm formation. Microbiology 154:1802-1812.
Felek, S., L. M. Runco, D. G. Thanassi, and E. S. Krukonis. 2007. Characterization of six novel chaperone/usher systems in Yersinia pestis. Adv Exp Med Biol 603:97-105.
Krukonis, E. S., and V. J. DiRita. 2003. DNA binding and ToxR responsiveness by the wing domain of TcpP, an activator of virulence gene expression in Vibrio cholerae. Mol Cell 12:157-165. cover article
Krukonis, E. S., and V. J. DiRita. 2003. From motility to virulence: sensing and responding to environmental signals in Vibrio cholerae. Curr Op Micro 6:186-190.