ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Bacterial Pathogenesis
Virulence and genome analysis of three historical Francisella tularensis ssp. holarctica isolates for development of a Type B test panel
Provisionally accepted
Kevin D Mlynek1*
Joshua B Richardson2
Elsie E Martinez1Ronald G Toothman1Ju Qiu3Curtis R Cline4
Joel A Bozue1*- 1Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, United States
- 2Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, United States
- 3Regulated Research Administration Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, United States
- 4Pathology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, United States
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Francisella tularensis ssp. tularensis (Type A) and ssp. holarctica (Type B) are the etiological agent of tularemia. Most studies on F. tularensis pathogenesis and vaccine development have focused on the Type A Schu S4 strain. However, Type B isolates remain less understood, emphasizing the need for further research. To address this concern and provide well characterized Type B isolates to test future vaccine efficacy, we selected three Type B isolates available in the USAMRIID repository (VT68, strain 425, and strain 503). These strains were chosen based on the original isolation source, the availability of historical in vivo data, and genomic sequence data. Strains were characterized for extracellular and intracellular growth, lipopolysaccharide profile via western blot analysis, and LD50 values were determined by both murine intranasal challenge and aerosolization of Fischer 344 rats. Strain 425 displayed several attenuation indicators and was completely attenuated in a rat aerosol challenge model. In contrast, VT68 and 503 remained highly virulent in rodent models but displayed some differences in lesion severity. Although F. tularensis genomes are known to be highly conserved, genomic analysis revealed multiple inversions and 68 unique genetic differences among these three Type B isolates. From this study, we were able to provide well-characterized Type B F. tularensis strains to test future vaccines and therapeutics.
Keywords: Francisella tularensis, Type B, Holarctica, rat, Animal modeling, Tularemia, pathogenicity
Received: 04 Aug 2025; Accepted: 11 Nov 2025.
Copyright: © 2025 Mlynek, Richardson, Martinez, Toothman, Qiu, Cline and Bozue. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Kevin D Mlynek, kevin.d.mlynek.civ@health.mil
Joel A Bozue, joel.a.bozue.civ@health.mil
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