Towards rapid stable isotope breath test detection of inhalational tularemia

Towards rapid stable isotope breath test detection of inhalational tularemia

Graham S Timmins 1, Alexander Dekonenko 2, Audrey Nava 2, Seong Won Choi 1, and Terry H. Wu 2

1. Department of Pharmaceutical Sciences, College of Pharmacy and

2. Center for Infectious Disease & Immunity,Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM

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Abstract: 

A mass outbreak of inhalational tularemia caused by bioweapon (BW) aerosol exposure to Francisella tularensis remains a potentially devastating threat. Here we describe early steps in the development of a novel breath test diagnostic for pneumonic tularemia BW events. F. tularensis expresses a unique enzyme, and known virulence factor citrulline ureidase, (CTU) an enzyme important in disrupting the NO mediated innate immunity, and in counteracting against intracellular acidification in phagosomes. CTU catalyzes the hydrolysis of citrulline to ornithine, ammonia and CO2, and we hypothesized we could use selectively 13C-labeled citrulline to produce labelled carbon dioxide by CTU activity in a similar manner to urease breath testing. The significant biosafety challenges in studying a Tier 1 select agent both in vitro and in vivo (mouse model) were overcome and may prove informative for breath test studies of other high containment organisms. Detection of CTU activity was possible in vitro and in breath from the mouse model.