Identification of Yersinia pestis Transmission Factors

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Abstract In the event of a bioterrorist attack, clinical microbiologists would be among the first health professionals to encounter specimens containing biowarfare agents. Therefore, microbiologists trained in recognizing and handling these agents would be a valuable resource for outbreak detection and surveillance. For this Career Development application, we propose Dr. Fisher train to become a clinical microbiology director so that he may bring a knowledge of biodefense, and thereby help expand bioterrorism preparedness, to the public health setting. For the research component of the training, Dr. Fisher will identify transmission factors of Yersinia pestis. Y. pestis is a Category A priority select agent with the ability to produce rapidly fatal disease and be transmitted by both aerosol and flea-bite. Because "plague" is immediately recognized by the public as a deadly epidemic disease, even minor outbreaks would likely cause great panic. These factors contribute to the fact that Y. pestis has enormous potential as an agent of bioterrorism. Although it has been recognized for nearly a century that Y. pestis can infect and be transmitted by fleas, little is known of the mechanisms that enable this phenotype. The fact that Y. pestis-infected fleas have been used as biowarfare agents in the past suggests they might be used for purposes of bioterrorism. Molecular genetic tools which take advantage of pool-based selection and screening of mutants/constructs will be used to examine the interaction between Y. pestis and an efficient flea vector of plague transmission, Xenopsylla cheopis. Specifically, signature-tagged mutagenesis (STM) and the in-vivo expression technology (IVET), which have both been used successfully in Yersinia spp., will be applied to this system to identify the genetic factors involved in the Y. pestis-flea relationship. Currently, there is not a licenced plague vaccine in this country, and the vaccine candidates in development are based on only two antigens (F1 and V) that each have potential problems. In addition, most plague diagnostic reagents are based on a single protein (F1 antigen) or its gene, which could be problematic since this marker is not universally present in Y. pestis. Identification of Y. pestis transmission factors may lead to novel plague vaccine candidates and diagnostics with fewer inherent problems than current reagents.