A Francisella tularensis pathogenicity island required for intramacrophage growth.

Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
Journal of Bacteriology (Impact Factor: 2.69). 11/2004; 186(19):6430-6. DOI: 10.1128/JB.186.19.6430-6436.2004
Source: PubMed

ABSTRACT Francisella tularensis is a gram-negative, facultative intracellular pathogen that causes the highly infectious zoonotic disease tularemia. We have discovered a ca. 30-kb pathogenicity island of F. tularensis (FPI) that includes four large open reading frames (ORFs) of 2.5 to 3.9 kb and 13 ORFs of 1.5 kb or smaller. Previously, two small genes located near the center of the FPI were shown to be needed for intramacrophage growth. In this work we show that two of the large ORFs, located toward the ends of the FPI, are needed for virulence. Although most genes in the FPI encode proteins with amino acid sequences that are highly conserved between high- and low-virulence strains, one of the FPI genes is present in highly virulent type A F. tularensis, absent in moderately virulent type B F. tularensis, and altered in F. tularensis subsp. novicida, which is highly virulent for mice but avirulent for humans. The G+C content of a 17.7-kb stretch of the FPI is 26.6%, which is 6.6% below the average G+C content of the F. tularensis genome. This extremely low G+C content suggests that the DNA was imported from a microbe with a very low G+C-containing chromosome.

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    ABSTRACT: Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD) protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP). The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.
    PLoS Pathogens 10/2014; 10(10):e1004439. DOI:10.1371/journal.ppat.1004439 · 8.14 Impact Factor
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    ABSTRACT: Background / Purpose: Francisella is a gram negative bacterium highly virulent in fishes and human. Tilapia fishes are used as food resources and to control undesired aquatic plants. Francisella is causing serious problems in Tilapia that leads to mortality. The strain which is infecting Tilapia is called Francisella orientalis. It would be of high value to better understand the biology and virulence of the Francisella orientalis. We have completed the sequencing and assembly of the Francisella orientalis strain. The genome is around 1.9mbp and the GC content is 32%.We predicted 1450 protein coding genes, 300 pseudo-genes, 32 t-RNAs, 2 5s-rRNAs, one each from 23s-RNA and 16s-RNA. Main conclusion: We have not found genes encoding any other type of RNAs though it is not uncommon in prokaryotes. Whole genome phylogenetic analyses including the other publicly available Francisella genomes indicates that the evolutionary split between Francisella orientalis and the other strains is ancient and fairly close to time to the divergence of the Francisella philomiragia, which is non virulent to human. Further analysis reveals that all the genomes are highly rearranged relative to each other.
    Intelligent Systems for Molecular Biology 2010 meeting; 07/2010
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    ABSTRACT: Francisella tularensis is an intracellular Gram-negative bacterium that causes life-threatening tularemia. Although the prevalence of natural infection is low, F. tularensis remains a tier I priority pathogen due to its extreme virulence and ease of aerosol dissemination. F. tularensis can infect a host through multiple routes, including the intradermal and respiratory routes. Respiratory infection can result from a very small inoculum (ten organisms or fewer) and is the most lethal form of infection. Following infection, F. tularensis employs strategies for immune evasion that delay the immune response, permitting systemic distribution and induction of sepsis. In this review we summarize the current knowledge of F. tularensis in an immunological context, with emphasis on the host response and bacterial evasion of that response.
    Infection and Drug Resistance 09/2014; 7:239-51. DOI:10.2147/IDR.S53700

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