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

Genetic identification of unique immunological responses in mice infected with virulent and attenuated Francisella tularensis

Francisella tularensis is a category A select agent based on its infectivity and virulence but disease mechanisms in infection remain poorly understood. Murine pulmonary models of infection were therefore employed to assess and compare dissemination and pathology and to elucidate the host immune response to infection with the highly virulent Type A F. tularensis strain Schu4 versus the less virulent Type B live vaccine strain (LVS). We found that dissemination and pathology in the spleen was significantly greater in mice infected with F. tularensis Schu4 compared to mice infected with F. tularensis LVS. Using gene expression rofiling to compare the response to infection with the two F. tularensis strains, we found that there were significant differences in the expression of genes involved in the apoptosis pathway, antigen processing and presentation pathways, and inflammatory response pathways in mice infected with Schu4 when compared to LVS. These transcriptional differences coincided with marked differences in dissemination and severity of organ lesions in mice infected with the Schu4 and LVS strains. Therefore, these findings indicate that altered apoptosis, antigen presentation and production of inflammatory mediators explain the differences in pathogenicity of F. tularensis Schu4 and LVS

Comparative review of F. tularensis and F. novicida

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

The Ly49 gene family. A brief guide to the nomenclature, genetics, and role in intracellular infection.

Understanding the Ly49 gene family can be challenging in terms of nomenclature and genetic organization. The Ly49 gene family has two major gene nomenclature systems, Ly49 and Killer Cell Lectin-like Receptor subfamily A (klra). Mice from different strains have varying numbers of these genes with strain specific allelic variants, duplications, deletions, and pseudogene sequences. Some members activate NK lymphocytes, invariant NKT lymphocytes and γδ T lymphocytes while others inhibit killing activity. One molecule, Ly49Q, is not found on NK cells at all, rather is expressed only on myeloid cells. There is growing evidence that these receptors may regulate not just the immune response to viruses, but other intracellular pathogens as well. Thus, this review's primary goal is to provide a guide for researchers first encountering the Ly49 gene family and a foundation for future studies on the role that these gene products play in the immune response, particularly the response to intracellular viral and bacterial pathogens

Plasmid based protein composition of <i>B</i>. <i>mayonii</i> in comparison to 4 other Bbsl genospecies and 1 RF <i>Borrelia</i> species.

<p>The mean amino acid identity is indicated for proteins present on each of the 14 <i>B</i>. <i>mayonii</i> plasmids. Comparisons are to protein databases constructed for <i>B</i>. <i>burgdorferi</i> (B.b.s.s.; green), <i>B</i>. <i>garinii</i> (B.g.; blue), <i>B</i>. <i>afzelii</i> (B. a.; red), <i>B</i>. <i>bissettii</i> (B.b.; yellow), and <i>B</i>. <i>miyamotoi</i> (B.m.; grey).</p

<i>B</i>. <i>mayonii</i> proteins with greatest sequence diversity as compared to 4 other Bbsl genospecies and 1 RF Borrelia species.

<p>Bar graph depicting <i>B</i>. <i>mayonii</i> proteins greater than 100 amino acids with less than 60% amino acid identity to other Bbsl proteins. Amino acid identity is shown with respect to homologs present in <i>B</i>. <i>burgdorferi</i> (B.b.s.s.; green), <i>B</i>. <i>garinii</i> (B.g.; blue), <i>B</i>. <i>afzelii</i> (B. a.; red), <i>B</i>. <i>bissettii</i> (B.b.; yellow) and <i>B</i>. <i>miyamotoi</i> (B.m.; grey).</p

Nucleotide differences detected between <i>B. mayonii</i> strains MN14-1420 and MN14-1539^*.

<p>Nucleotide differences detected between <i>B. mayonii</i> strains MN14-1420 and MN14-1539^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168994#t003fn001" target="_blank">*</a>}.</p

<i>vls</i> containing linear plasmid lp28-10 from <i>B</i>. <i>mayonii</i> MN14-1420 and MN14-1539.

<p>A) Heat map displaying nucleotide identity (blue—lowest; yellow—highest) between the active <i>vlsE</i> nucleotide sequence (magenta arrow) and silent <i>vls</i> cassettes within the two <i>B</i>. <i>mayonii</i> strains. Position and copy number of the silent cassette array is indicated by the blue to yellow ribbons. Red bars indicate silent <i>vls</i> loci present in MN14-1420 and missing in MN14-1539. Genes flanking the <i>vls</i> locus are indicated by black arrows. Orientation of arrows indicates gene orientation on the forward or reverse DNA strand. B) Multi-alignment of the 26 amino acid C6 peptide within VlsE from <i>B</i>. <i>mayonii</i>, <i>B</i>. <i>burgdorferi</i> B31 and <i>B</i>. <i>garinii</i> IP90. Identical (*), conserved (:) and differentially charged (.) amino acid residues are indicated.</p

Putative <i>B</i>. <i>burgdorferi</i> plasmid-borne proteins absent from the <i>B</i>. <i>mayonii</i> genome.

<p>Putative <i>B</i>. <i>burgdorferi</i> plasmid-borne proteins absent from the <i>B</i>. <i>mayonii</i> genome.</p