Abstract
Francisella tularensis is the causative agent of the acute disease tularemia. Due to its extreme infectivity and ability to cause disease upon inhalation, F. tularensis has been classified as a biothreat agent. Two subspecies of F. tularensis, tularensis and holarctica, are responsible for tularemia in humans. In comparison, the closely related species F. novicida very rarely causes human illness and cases that do occur are associated with patients who are immune compromised or have other underlying health problems. Virulence between F. tularensis and F. novicida also differs in laboratory animals. Despite this varying capacity to cause disease, the two species share ~97% nucleotide identity, with F. novicida commonly used as a laboratory surrogate for F. tularensis. As the F. novicida U112 strain is exempt from U.S. select agent regulations, research studies can be carried out in non-registered laboratories lacking specialized containment facilities required for work with virulent F. tularensis strains. This review is designed to highlight phenotypic (clinical, ecological, virulence, and pathogenic) and genomic differences between F. tularensis and F. novicida that warrant maintaining F. novicida and F. tularensis as separate species. Standardized nomenclature for F. novicida is critical for accurate interpretation of experimental results, limiting clinical confusion between F. novicida and F. tularensis and ensuring treatment efficacy studies utilize virulent F. tularensis strains.
Highlights
AND OVERVIEW F. tularensis was first isolated in 1912 as the causative agent of a plague-like disease affecting squirrels in Tulare county, California (McCoy and Chapin, 1912)
Genomic analyses of F. novicida U112, F. tularensis subsp. tularensis Schu S4, and F. tularensis subsp. holarctica LVS indicate 41.2 percent of the genes predicted to be involved in amino acid biosynthesis in F. novicida U112 are inactivated in one or both F. tularensis strains (Rohmer et al, 2007)
As recent studies indicate virulence differs among F. tularensis subsp. tularensis strains in humans (Kugeler et al, 2009; Molins et al, 2010), the use of more virulent A1b strains should be considered for therapeutic efficacy testing in animals
Summary
AND OVERVIEW F. tularensis was first isolated in 1912 as the causative agent of a plague-like disease affecting squirrels in Tulare county, California (McCoy and Chapin, 1912). It is problematic when trying to interpret published experimental results obtained using F. novicida U112, but described only as F. tularensis with no strain information included Another negative outcome of the proposed classification of F. novicida as a subspecies of F. tularensis is that other F. novicida strains, excluding the exempt U112 strain, are considered select agents in the US, despite the fact they do not cause tularemia. Hallmarks of tularemia in healthy individuals, were only observed for F. novicida infections in compromised patients (Hollis et al, 1989; Clarridge et al, 1996; Leelaporn et al, 2008; Brett et al, 2012; Respicio-Kingry et al, 2012; Whitehouse et al, 2012). In the two healthy individuals with F. novicida infection, regional lymphadenopathy, www.frontiersin.org
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