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About the Authors:
Sarmistha Bandyopadhyay
Affiliations Inflammation Program, University of Iowa, Coralville, Iowa, United States of America, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America, Veteran's Administration Medical Center, Iowa City, Iowa, United States of America
Matthew E. Long
Affiliations Inflammation Program, University of Iowa, Coralville, Iowa, United States of America, Graduate Training Program in Molecular and Cellular Biology, University of Iowa, Iowa City, Iowa, United States of America
Lee-Ann H. Allen
* E-mail: [email protected]
Affiliations Inflammation Program, University of Iowa, Coralville, Iowa, United States of America, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America, Graduate Training Program in Molecular and Cellular Biology, University of Iowa, Iowa City, Iowa, United States of America, Veteran's Administration Medical Center, Iowa City, Iowa, United States of America
Introduction
Francisella tularensis is a facultative intracellular Gram-negative bacterium that causes the zoonotic disease tularemia [1]. This organism infects over 200 types of animals in nature and can be transmitted to humans through insect bites, ingestion of contaminated food and water, or direct contact with infected animals or aerosolized bacteria. Indeed, inhalation of as few as 10 organisms of the highly virulent F. tularensis subspecies tularensis (type A) strains can be lethal to otherwise healthy individuals, whereas infection with F. tularensis subspecies holarctica (type B) is typically less severe [1], [2]. Due to its high infectivity, ease of dissemination, and potential lethality, F. tularensis is considered a candidate bioweapon. Both type A and type B strains of this pathogen have been classified as Tier 1 select agents, and their possession and study are tightly regulated [1], [3]. An attenuated type B strain was derived several decades ago, but this live vaccine strain (LVS) is not currently licensed for use in the United States [4]. LVS retains many key features of virulent type A and type B F. tularensis during in vitro infection of eukaryotic cells but does not require biosafety level-3 (BSL-3) containment, and for this reason is an attractive model for studies of tularemia pathogenesis [1], [4], [5].
F. tularensis infects several cell types, but macrophages are the major site of bacterial replication in vivo and also act as vehicles for bacterial dissemination from the site of...