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About the Authors:
Zachary W. Bent
* E-mail: [email protected]
Affiliation: Sandia National Laboratories, Livermore, California, United States of America
David M. Brazel
Affiliation: Sandia National Laboratories, Livermore, California, United States of America
Mary B. Tran-Gyamfi
Affiliation: Sandia National Laboratories, Livermore, California, United States of America
Rachelle Y. Hamblin
Affiliation: Sandia National Laboratories, Livermore, California, United States of America
Victoria A. VanderNoot
Affiliation: Sandia National Laboratories, Livermore, California, United States of America
Steven S. Branda
Affiliation: Sandia National Laboratories, Livermore, California, United States of America
Introduction
Francisella tularensis, the causative agent of tularemia, is a Gram-negative facultative intracellular pathogen that is capable of infecting a wide variety of hosts, including mammals, birds, amphibians, fish, and insects [1]. Originally isolated in 1911 in Tulare County, California during a plague-like outbreak in the rodent population, F. tularensis was subsequently found to be endemic in most of the northern hemisphere [2]. Human infections most commonly occur upon contact with infected animals or from the bite of an infected tick, leading to cutaneous ulceroglandular tularemia [3]. A pneumonic infection can result from inhalation of as few as 10 bacteria, leading to severe and often fatal disease [4]. Because of the seriousness of its disease, ability to be aerosolized, and extremely low infectious dose, F. tularensis has long been feared for its potential as a biological weapon and has been designated a Category A Select Agent [5,6]. The species F. tularensis is comprised of two sub-species types, with type A strains endemic to North America and type B strains endemic to Europe and Asia [2]. A live vaccine strain (LVS) derived from a type B strain was created in the former Soviet Union over 50 years ago; due to safety concerns, however, it is not currently licensed for human use [7]. Although the F. tularensis LVS strain does not cause illness in humans, it is lethal to mice, causing a disease that very closely mimics human tularemia [8]. These features have made the F. tularensis LVS murine infection model an ideal and well-established system for study of F. tularensis pathogenesis [9].
As an intracellular pathogen, F. tularensis must adapt to multiple environments throughout the course of an infection. The bacteria enter host cells via phagocytosis, escape the phagosome, replicate...