Tuesday, July 31, 2007 - 9:25 AM
S67

Discovery and use of molecular signatures for biological threat agents: examples using Bacillus anthracis, Yersinia pestis, and Francisella tularensis

David M. Wagner and Paul Keim. Department of Biological Sciences, Northern Arizona University, PO Box 5640, Flagstaff, AZ 86011-5640

Bacillus anthracis, Yersinia pestis, and Francisella tularensis are the causative agents of anthrax, plague, and tularemia, respectively. Although all three species are important natural disease threats, each also has been developed, and sometimes used, as a biological weapon by state-sponsored programs and/or bioterrorists. Precise strain identification plays a crucial role in attribution following the nefarious use of these agents. We have discovered and developed highly-specific molecular signatures that can be used to rapidly identify and characterize these three pathogens. We utilize multiple signature types in a hierarchical approach to both assign an unknown isolate to major phylogenetic groups and provide maximum resolving power. However, strain identification by itself often is not sufficient. To determine the identity of an unknown strain it is necessary to compare the molecular fingerprint of that strain to a database containing molecular fingerprints from a diverse collection of known strains. If a perfect match is found, then the unknown strain can be identified. If no perfect match is found, it requires the investigators to determine what constitutes a “near match”. These types of determinations can be subjective. To add objectivity to this approach, we have developed a Bayesian or likelihood approach based upon empirically-derived mutation rates at VNTR markers. We will illustrate these various approaches using Bacillus anthracis, Yersinia pestis, and Francisella tularensis as examples.

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