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: 2.81). 11/2004; 186(19):6430-6. DOI: 10.1128/JB.186.19.6430-6436.2004
Source: PubMed


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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    • "MglB Macrophage growth locus, subunit B IG F. novicida U112 J774 [71] MigR Macrophage intracellular growth regulator PE LVS BMMs [63] IG LVS BMMs [63] LVS dMDMs [72] PdpA Pathogenicity deteminant protein pdpA PE F. novicida U112 BMMs/J774 [73] IG F. novicida U112 BMMs/J774 [48] PdpB Pathogenicity deteminant protein pdpB IG F. novicida U112 BMMs/J774 [73] PmrA Orphan response regulator IG F. novicida U112 THP-1/J774 [74] PurA Adenylosuccinate synthetase IG F. novicida U112 J774 [75] table modified from [264] "
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    ABSTRACT: Tularemia is a debilitating febrile and potentially fatal zoonotic disease of humans and other vertebrates caused by the Gram-negative bacterium Francisella tularensis. The natural reservoirs are small rodents, hares, and possibly amoebas in water. The etiological agent, Francisella tularensis, is a non-spore forming, encapsulated, facultative intracellular bacterium, a member of the γ-Proteobacteria class of Gram-negative bacteria. Francisella tularensis is capable of invading and replicating within phagocytic as well as non-phagocytic cells and modulate inflammatory response. Infection by the pulmonary, dermal, or oral routes, respectively, results in pneumonic, ulceroglandular, or oropharyngeal tularemia. The highest mortality rates are associated with the pneumonic form of this disease. All members of Francisella tularensis species cause more or less severe disease Due to their abilities to be transmitted to humans via multiple routes and to be disseminated via biological aerosol that can cause the disease after inhalation of even an extremely low infectious dose, Francisella tularensis has been classified as a Category A bioterrorism agent. The current standard of care for tularemia is treatment with antibiotics, as this therapy is highly effective if used soon after infection, although it is not, however, absolutely effective in all cases.
    Full-text · Article · Mar 2015 · Central European Journal of Biology
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    • "It contains 17 open reading frames of varying size, several of which have been identified as essential for pathogenesis.19 Intriguingly, the Francisella pathogenicity island is characterized by a lower percentage of guanine and cytosine nucleotides compared with the rest of the Francisella genome, which itself has a fairly low guanine and cytosine content.18,19 In the study that identified the Francisella pathogenicity island, the pdpA gene was identified as being essential for virulence, but its function and the functions of the other pdp genes are not known.19,20 "
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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.
    Full-text · Article · Sep 2014 · Infection and Drug Resistance
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    • "The ClpB protein is a protease induced by heat stress that helps to disperse and restructure denatured proteins. Studies carried out for F. tularensis located within the macrophage indicate that mutations within the coding sequence of ClpB provoke a reduction in the growth capacity of this microorganism (Nano et al., 2004). For its part, virulence factor BipA is a highly conserved protein described in L. pneumophila, C. burnetii, and F. tularensis. "
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    ABSTRACT: Piscirickettsia salmonis is the pathogen responsible for salmonid rickettsial septicemia (SRS), a disease that affects a wide variety of marine cultivated fish species and causes economic losses for the aquaculture industry worldwide. Many in vitro studies have reported on the capacity of this microorganism to replicate in the interior of cytoplasmic vesicles from varied fish cell lines. However, the mechanisms used by this bacteria to survive, replicate, and propagate in cell lines, especially in macrophages and monocytes, are unknown. A number of studies have described the diverse proteins in pathogens such as Legionella pneumophila, Coxiella burnetii, and Francisella tularensis which allow these to evade the cellular immune response and replicate in the interior of macrophages in different hosts. Some of these proteins are the virulence factor BipA/TypA and the heat shock protein ClpB, both of which have been widely characterized. The results of the current study present the complete coding sequence of the genes clpB and bipA from the P. salmonis genome. Moreover, the experimental results suggest that during the infectious process of the SHK-1 cellular line in P. salmonis, the pathogen significantly increases the expression of proteins ClpB and BipA. This would permit the pathogen to adapt to the hostile conditions produced by the macrophage and thus evade mechanisms of cellular degradation while facilitating replication in the interior of this salmon cell line.
    Full-text · Article · Aug 2014 · Veterinary Microbiology
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