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 Yersinia pestis required for virulence. Y. pestis is the causative agent of plague. We are investigating the role of the outer membrane proteins Ail and Pla (plasminogen activator) as well as chaperone/usher–dependent pili such as pH 6 antigen (Psa) that facilitate the delivery of cytotoxic Yop proteins to host cells. All three adhesins contribute to Y. pestis virulence. 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.
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