Yersinia pestis and Bacillus anthracis are designated by the Centers for Disease Control and Prevention (CDC) as Category A bacterial pathogens and are the etiological agents for the plague and anthrax, respectively. Although the natural occurrence of each disease is rare, the possibility of terrorist groups using these pathogens as bioweapons is real. Because both conditions share common features such as rapid clinical course, and high mortality, it is critical that outbreaks be detected quickly. Therefore, methodologies that provide rapid detection and diagnosis are essential to ensure immediate implementation of public health measures and activation of crisis management. The goal of this research is to develop a diagnostic platform for the plague and anthrax. The CDC currently uses classical phage lysis assays as a standard for the confirmed identification of Y. pestis and B. anthracis. Although these assays are robust, they are laboratory based and require 24-48 h to complete. In order to overcome these limitations, we have generated recombinant light-tagged-reporter phages which can rapidly (within minutes), sensitively and specifically transduce a bioluminescent phenotype to Y. pestis and B. anthracis. We have demonstrated that the reporter phages can detect the target pathogens at clinically relevant concentrations during the early course of disease, and also generate antibiotic susceptibility profiles 5 to 10 times faster than conventional methods. This is key as the diseases are treatable as long as they are rapidly diagnosed, and appropriate therapy is initiated. We will continue with this research and transition the diagnostic technology to preclinical development with the goal of gaining FDA-approval. In the NIAID: Strategic Planning for the 21st Century, NIAID highlights the following priorities in the development of diagnostic assays: (i) specific to the pathogen; (ii cost effective; (iii) sensitive; (iv) multiplexed and high throughput, and (v) easy to use. This proposal is significant because the reporter phage technology can address these requirements, and has the potential to save lives by significantly improving our nation's defense against biological warfare.

Public Health Relevance

Category A bacterial pathogens cause diseases that are usually fatal. Although the infections are treatable, early diagnosis and the administration of appropriate antibiotics is essential for a positive patient outcome. This proposal will develop a diagnostic technology that can rapidly detect the bacterial agent that causes disease, and also provide information as to which antimicrobial drug is most effective in fighting the infection. Thus, this research has the potential to save lives and significantly improve our nation's defense against biological warfare.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZAI1)
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Ritchie, Alec
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Guild Associates, Inc.
United States
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Nguyen, C; Makkar, R; Sharp, N J et al. (2017) Detection of Bacillus anthracis spores from environmental water using bioluminescent reporter phage. J Appl Microbiol 123:1184-1193
Sharp, Natasha J; Molineux, Ian J; Page, Martin A et al. (2016) Rapid Detection of Viable Bacillus anthracis Spores in Environmental Samples by Using Engineered Reporter Phages. Appl Environ Microbiol 82:2380-2387
Vandamm, J P; Rajanna, C; Sharp, N J et al. (2014) Rapid detection and simultaneous antibiotic susceptibility analysis of Yersinia pestis directly from clinical specimens by use of reporter phage. J Clin Microbiol 52:2998-3003