Host-Pathogen Interaction in Plague

PI: Dr. Carolyn Hovde Bohach

Director of the NIH Idaho INBRE Program
Department of Microbiology, Molecular Biology, and Biochemistry
University of Idaho, Moscow, ID

Dr. Scott Minnich

Associate Director of the NIH Idaho INBRE Program
Department of Microbiology, Molecular Biology, and Biochemistry
University of Idaho, Moscow, ID

This project previously focused on the development of novel vaccine and therapeutic strategies using Yersinia pestis models. We examined lipid A mimetics (aminoalkyl glucosaminide phosphates, AGPs), Toll-like receptor (TLR) 4 agonists. We found that AGPs directly protect against pneumonic plague, dramatically augment antibiotic therapy, and are efficacious adjuvants for either intranasal (i.n.) or subcutaneous (s.c.) vaccines containing Y. pestis capsular (F1) and/or V-antigens. Our vaccination regimen results in a rapid and sustained acquired TH1 immune response which protects in mouse and rat models. We also are characterizing several newly identified Y. pestis virulence factors and their regulation.

Significant advances have been made toward identifying additional virulence mechanisms by screening for attenuated strains using advanced bioinformatic analyses, comprehensive transposon libraries, and through animal and Caenorhabditis elegans models. The specific aims in this proposal expand on these successes by

  • Further examination of the transition between induction of innate immunity with TLR agonists and specific immunity directed against pneumonic plague
  • Determination of the role of regulatory genes and surface/extracellular proteins in Y. pestis infection and/or flea vector maintenance
  • Identification of natural mutations (pseudogenes) that are essential for Y. pestis pathogenesis