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    • "novicida (F. novicida), which may actually be a separate species (Johansson et al., 2010). Francisella is especially recognized for its low infectious dose and ability to cause severe illness and death, which justifies its categorization as a Category A select agent by the USA Centers for Disease Control and Prevention (CDC) (Sjostedt, 2007). "
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    ABSTRACT: Francisella tularensis can bypass and suppress host immune responses, even to the point of manipulating immune cell phenotypes and intercellular inflammatory networks. Strengthening these responses such that immune cells more readily identify and destroy the bacteria is likely to become a viable (and perhaps necessary) strategy for combating infections with Francisella, especially given the likelihood of antibiotic resistance in the foreseeable future. Monocytes and macrophages offer a niche wherein Francisella can invade and replicate, resulting in substantially higher bacterial load that can overcome the host. As such, understanding their responses to Francisella may uncover potential avenues of therapy that could promote a lowering of bacterial burden and clearance of infection. These response pathways include Toll-like Receptor 2 (TLR2), the caspase-1 inflammasome, Interferons, NADPH oxidase, Phosphatidylinositide 3-kinase (PI3K), and the Ras pathway. In this review we summarize the literature pertaining to the roles of these pathways during Francisella infection, with an emphasis on monocyte/macrophage responses. The therapeutic targeting of one or more such pathways may ultimately become a valuable tool for the treatment of tularemia, and several possibilities are discussed.
    Frontiers in Cellular and Infection Microbiology 02/2014; 4:18. DOI:10.3389/fcimb.2014.00018 · 3.72 Impact Factor
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    • "mediasiatica) [1, 2]. However, the taxonomic boundaries of Francisella novicida have recently been debated [3, 4]. Two subspecies are of clinical importance: type A (F. tularensis subsp. "
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    ABSTRACT: In Sweden, mosquitoes are considered the major vectors of the bacterium Francisella tularensis subsp. holarctica, which causes tularaemia. The aim of this study was to investigate whether mosquitoes acquire the bacterium as aquatic larvae and transmit the disease as adults. Mosquitoes sampled in a Swedish area where tularaemia is endemic (Örebro) were positive for the presence of F. tularensis deoxyribonucleic acid throughout the summer. Presence of the clinically relevant F. tularensis subsp. holarctica was confirmed in 11 out of the 14 mosquito species sampled. Experiments performed using laboratory-reared Aedes aegypti confirmed that F. tularensis subsp. holarctica was transstadially maintained from orally infected larvae to adult mosquitoes and that 25 % of the adults exposed as larvae were positive for the presence of F. tularensis-specific sequences for at least 2 weeks. In addition, we found that F. tularensis subsp. holarctica was transmitted to 58 % of the adult mosquitoes feeding on diseased mice. In a small-scale in vivo transmission experiment with F. tularensis subsp. holarctica-positive adult mosquitoes and susceptible mice, none of the animals developed tularaemia. However, we confirmed that there was transmission of the bacterium to blood vials by mosquitoes that had been exposed to the bacterium in the larval stage. Taken together, these results provide evidence that mosquitoes play a role in disease transmission in part of Sweden where tularaemia recurs.
    Microbial Ecology 09/2013; 67(1). DOI:10.1007/s00248-013-0285-1 · 3.12 Impact Factor
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    • "philomiragia x F. novicida) causing disease predominantly in humans with a compromised immune defense [4]. The taxonomic boundaries of Francisella have recently been debated, in particular for F. novicida[5,6]. Recent breakthroughs in sequencing techniques have enabled public access to whole-genome sequences that can shed light on previously unknown diversity within the Francisella genus. "
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    ABSTRACT: Background Recent advances in sequencing technologies offer promising tools for generating large numbers of genomes, larger typing databases and improved mapping of environmental bacterial diversity. However, DNA-based methods for the detection of Francisella were developed with limited knowledge about genetic diversity. This, together with the high sequence identity between several Francisella species, means there is a high risk of false identification and detection of the highly virulent pathogen Francisella tularensis. Moreover, phylogenetic reconstructions using single or limited numbers of marker sequences often result in incorrect tree topologies and inferred evolutionary distances. The recent growth in publicly accessible whole-genome sequences now allows evaluation of published genetic markers to determine optimal combinations of markers that minimise both time and laboratory costs. Results In the present study, we evaluated 38 previously published DNA markers and the corresponding PCR primers against 42 genomes representing the currently known diversity of the genus Francisella. The results highlight that PCR assays for Francisella tularensis are often complicated by low specificity, resulting in a high probability of false positives. A method to select a set of one to seven markers for obtaining optimal phylogenetic resolution or diagnostic accuracy is presented. Conclusions Current multiple-locus sequence-typing systems and detection assays of Francisella, could be improved by redesigning some of the primers and reselecting typing markers. The use of only a few optimally selected sequence-typing markers allows construction of phylogenetic topologies with almost the same accuracy as topologies based on whole-genome sequences.
    BMC Microbiology 09/2012; 12(1):220. DOI:10.1186/1471-2180-12-220 · 2.73 Impact Factor
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