Comparative review of Francisella tularensis and Francisella novicida

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.

Towards Development of Improved Serodiagnostics for Tularemia by Use of Francisella tularensis Proteome Microarrays

“…F. tularensis subsp. novicida is relatively nonvirulent in healthy humans but has been responsible for a few rare cases of tularemia in immunodeficient individuals in the United States (7). The virulence of F. tularensis subsp.…”

Just When We Thought We Knew Everything We Needed To Know about Zn Acquisition and Bacterial Pathogenesis

“…But if F. novicida ZupT has the same properties that have been described in its counterparts in other bacteria (2), this importer would not be expected to provide this strain with an effective mechanism for overcoming the Zn sequestration defenses found in mammalian hosts. Maybe that is why F. novicida has not been isolated from mammals in the wild and is rarely associated with human infections (13). But it begs the question of why F. novicida U112 is so virulent in small doses in experimentally infected mice and guinea pigs (19).…”

“…tularensis strains cause the zoonotic disease tularemia (13). These bacteria infect a wide variety of wild mammals and are spread between these natural hosts and from these hosts to humans by arthropod vectors.…”

“…Francisella novicida, on the other hand, is a closely related bacterium that exhibits very low virulence for humans and can be handled safely under biosafety level 2 conditions but produces a rapidly fatal disease in experimentally infected mice. This combination of properties has made F. novicida a widely used surrogate for studying the biology and virulence of Francisella (13).…”

New anti-infective strategies for treatment of tularemia

“…Thus, F. tularensis strains with attenuated virulence have been used for decades in research laboratories, especially the F. novicida Utah 112 strain. In a comparative review, Kingry and Petersen (2014) clearly demonstrate that F. novicida should no longer be used as a surrogate of F. tularensis for therapeutic efficacy testing in animal models. These two bacteria strongly differ in their natural life cycle, behavior in phagocytes, immunomodulatory properties, and pathogenicity to humans.…”