Francisella tularensis: an arthropod-borne pathogen

Arthropod transmission of tularemia occurs throughout the northern hemisphere. Few pathogens show the adaptability of Francisella tularensis to such a wide array of arthropod vectors. Nonetheless, arthropod transmission of F. tularensis was last actively investigated in the first half of the 20th century. This review will focus on arthropod transmission to humans with respect to vector species, modes of transmission, geographic differences and F. tularensis subspecies and clades

Identification of \u3ci\u3eFrancisella tularensis\u3c/i\u3e subsp. \u3ci\u3etularensis \u3c/i\u3eA1 and A2 Infections by Real-Time Polymerase Chain Reaction

Francisella tularensis subsp. tularensis (type A) is subdivided into clades A1 and A2. Human tularemia infections caused by A1 and A2 differ with respect to clinical outcome; A1 infections are associated with a higher case fatality rate. In this study, we develop and evaluate TaqMan polymerase chain reaction (PCR) assays for identification of A1 and A2. Both assays were shown to be specific to either A1 or A2, with sensitivities of 10 genomic equivalents. Real-time PCR results for identification of A1 and A2 were in complete agreement with results obtained by pulsed field gel electrophoresis analysis or conventional PCR when specimens from sporadic tularemia cases and a tularemia outbreak involving both A1 and A2 were tested. In addition, outbreak samples not previously typed to the clade level could be classified as A1 or A2. The assays described here provide new diagnostic tools with a level of sensitivity not previously available for identification of A1 and A2 infections

Identification of \u3ci\u3eFrancisella tularensis\u3c/i\u3e subsp. \u3ci\u3etularensis \u3c/i\u3eA1 and A2 Infections by Real-Time Polymerase Chain Reaction

Francisella tularensis subsp. tularensis (type A) is subdivided into clades A1 and A2. Human tularemia infections caused by A1 and A2 differ with respect to clinical outcome; A1 infections are associated with a higher case fatality rate. In this study, we develop and evaluate TaqMan polymerase chain reaction (PCR) assays for identification of A1 and A2. Both assays were shown to be specific to either A1 or A2, with sensitivities of 10 genomic equivalents. Real-time PCR results for identification of A1 and A2 were in complete agreement with results obtained by pulsed field gel electrophoresis analysis or conventional PCR when specimens from sporadic tularemia cases and a tularemia outbreak involving both A1 and A2 were tested. In addition, outbreak samples not previously typed to the clade level could be classified as A1 or A2. The assays described here provide new diagnostic tools with a level of sensitivity not previously available for identification of A1 and A2 infections

Ecological Niche Modeling of Francisella tularensis Subspecies and Clades in the United States

Two subspecies of Francisella tularensis are recognized: F. tularensis subsp. tularensis (type A) and F. tularensis subsp. holartica (type B). Type A has been subdivided further into A1a, A1b, and A2, which differ geographically and clinically. The aim of this work was to determine whether or not differences among subspecies and clades translate into distinct ecological niches. We used 223 isolates from humans and wildlife representing all six genotypes (type A, B, A1, A2, A1a, or A1b). Ecological-niche models were built independently for each genotype, using the genetic algorithm for rule-set prediction. The resulting models were compared using a non-parametric multivariate analysis-of-variance method. A1 and A2 are ecologically distinct, supporting the previously observed geographic division, whereas ecological niches for types A and B overlapped notably but A1a and A1b displayed no appreciable differences in their ecological niches

Virulence difference between the prototypic Schu S4 strain (A1a) and Francisella tularensisA1a, A1b, A2 and type B strains in a murine model of infection

BACKGROUND: The use of prototypic strains is common among laboratories studying infectious agents as it promotes consistency for data comparability among and between laboratories. Schu S(4) is the prototypic virulent strain of Francisella tularensis and has been used extensively as such over the past six decades. Studies have demonstrated virulence differences among the two clinically relevant subspecies of F. tularensis, tularensis (type A) and holarctica (type B) and more recently between type A subpopulations (A1a, A1b and A2). Schu S(4) belongs to the most virulent subspecies of F. tularensis, subspecies tularensis. METHODS: In this study, we investigated the relative virulence of Schu S(4) in comparison to A1a, A1b, A2 and type B strains using a temperature-based murine model of infection. Mice were inoculated intradermally and a hypothermic drop point was used as a surrogate for death. Survival curves and the length of temperature phases were compared for all infections. Bacterial burdens were also compared between the most virulent type A subpopulation, A1b, and Schu S(4) at drop point. RESULTS: Survival curve comparisons demonstrate that the Schu S(4) strain used in this study resembles the virulence of type B strains, and is significantly less virulent than all other type A (A1a, A1b and A2) strains tested. Additionally, when bacterial burdens were compared between mice infected with Schu S(4) or MA00-2987 (A1b) significantly higher burdens were present in the blood and spleen of mice infected with MA00-2987. CONCLUSIONS: The knowledge gained from using Schu S(4) as a prototypic virulent strain has unquestionably advanced the field of tularemia research. The findings of this study, however, indicate that careful consideration of F. tularensis strain selection must occur when the overall virulence of the strain used could impact the outcome and interpretation of results

Multiple Francisella tularensis Subspecies and Clades, Tularemia Outbreak, Utah

In July 2007, a deer fly–associated outbreak of tularemia occurred in Utah. Human infections were caused by 2 clades (A1 and A2) of Francisella tularensis subsp. tularensis. Lagomorph carcasses from the area yielded evidence of infection with A1 and A2, as well as F. tularensis subsp. holarctica. These findings indicate that multiple subspecies and clades can cause disease in a localized outbreak of tularemia

Epidemiologic and Molecular Analysis of Human Tularemia, United States, 1964–2004

Distinct subpopulations of F. tularensis differ in their clinical manifestations, geographic distribution, and likely modes of transmission

Whole genome single nucleotide polymorphism based phylogeny of Francisella tularensis and its application to the development of a strain typing assay

<p>Abstract</p> <p>Background</p> <p>A low genetic diversity in <it>Francisella tularensis </it>has been documented. Current DNA based genotyping methods for typing <it>F. tularensis </it>offer a limited and varying degree of subspecies, clade and strain level discrimination power. Whole genome sequencing is the most accurate and reliable method to identify, type and determine phylogenetic relationships among strains of a species. However, lower cost typing schemes are necessary in order to enable typing of hundreds or even thousands of isolates.</p> <p>Results</p> <p>We have generated a high-resolution phylogenetic tree from 40 <it>Francisella </it>isolates, including 13 <it>F. tularensis </it>subspecies <it>holarctica </it>(type B) strains, 26 <it>F. tularensis </it>subsp. <it>tularensis </it>(type A) strains and a single <it>F. novicida </it>strain. The tree was generated from global multi-strain single nucleotide polymorphism (SNP) data collected using a set of six Affymetrix GeneChip^®resequencing arrays with the non-repetitive portion of LVS (type B) as the reference sequence complemented with unique sequences of SCHU S4 (type A). Global SNP based phylogenetic clustering was able to resolve all non-related strains. The phylogenetic tree was used to guide the selection of informative SNPs specific to major nodes in the tree for development of a genotyping assay for identification of <it>F. tularensis </it>subspecies and clades. We designed and validated an assay that uses these SNPs to accurately genotype 39 additional <it>F. tularensis </it>strains as type A (A1, A2, A1a or A1b) or type B (B1 or B2).</p> <p>Conclusion</p> <p>Whole-genome SNP based clustering was shown to accurately identify SNPs for differentiation of <it>F. tularensis </it>subspecies and clades, emphasizing the potential power and utility of this methodology for selecting SNPs for typing of <it>F. tularensis </it>to the strain level. Additionally, whole genome sequence based SNP information gained from a representative population of strains may be used to perform evolutionary or phylogenetic comparisons of strains, or selection of unique strains for whole-genome sequencing projects.</p

Francisella tularensis Transmission by Solid Organ Transplantation, 20171.

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation