Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| oral live vaccine strain-induced protective immunity against pulmonary francisella tularensis challenge is mediated by cd4+ t cells and antibodies, including immunoglobulin a. | francisella tularensis is an intracellular gram-negative bacterium and the etiological agent of pulmonary tularemia. given the high degrees of infectivity in the host and of dissemination of bacteria following respiratory infection, immunization strategies that target mucosal surfaces are critical for the development of effective vaccines against this organism. in this study, we have characterized the efficacy of protective immunity against pneumonic tularemia following oral vaccination with f. ... | 2009 | 19211773 |
| an approach to the identification of t cell epitopes in the genomic era: application to francisella tularensis. | the identification and characterization of epitopes is essential for modern immunologic studies. here, we describe a novel methodology we have developed to identify t cell epitopes exploiting the phenomenon of cross presentation. particulate antigens, in the form of beads, are very effective in delivering exogenous antigen to both the class i and class ii pathways. we will review our efforts to screen entire genomes of pathogens for t cell epitopes taking advantage of the advances in genomics us ... | 2009 | 19212707 |
| intracellular fate of francisella tularensis within arthropod-derived cells. | since transmission of francisella tularensis into the mammalian host occurs via arthropod vectors such as ticks, mosquitoes, horseflies and deerflies, recent studies have established drosophila melanogaster as an arthropod vector model system. nothing is known about the intracellular fate of f. tularensis within arthropod-derived cells, and the role of this host-parasite adaptation in the evolution of this pathogen to infect mammals. in this report, we explored intracellular trafficking of f. tu ... | 2009 | 19220402 |
| hfq, a novel pleiotropic regulator of virulence-associated genes in francisella tularensis. | francisella tularensis is a highly infectious pathogen that infects animals and humans, causing tularemia. the ability to replicate within macrophages is central for virulence and relies on expression of genes located in the francisella pathogenicity island (fpi), as well as expression of other genes. regulation of fpi-encoded virulence gene expression in f. tularensis involves at least four regulatory proteins and is not fully understood. here we studied the rna-binding protein hfq in f. tulare ... | 2009 | 19223477 |
| identification of francisella tularensis subsp. tularensis a1 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 ... | 2009 | 19232853 |
| identification of a dominant cd4 t cell epitope in the membrane lipoprotein tul4 from francisella tularensis lvs. | francisella tularensis is a gram-negative intracellular bacterium that is the causative agent of tularemia. small mammals such as rodents and rabbits, as well as some biting arthropods, serve as the main vectors for environmental reservoirs of f. tularensis. the low infectious dose, ability to aerosolize the organism, and the possibility of generating antibiotic resistant strains make f. tularensis a prime organism for use in bioterrorism. as a result, some strains of f. tularensis have been pla ... | 2009 | 19233475 |
| t cells from lungs and livers of francisella tularensis-immune mice control the growth of intracellular bacteria. | parenteral and respiratory vaccinations with the intracellular bacterium francisella tularensis have been studied using the live vaccine strain (lvs) in a mouse model, and spleen cells from immune mice are often used for immunological studies. however, mechanisms of host immunological responses may be different in nonlymphoid organs that are important sites of infection, such as lung and liver. using parenteral (intradermal) or respiratory (cloud aerosol) vaccination, here we examine the functio ... | 2009 | 19237526 |
| francisella tularensis phagosomal escape does not require acidification of the phagosome. | following uptake, francisella tularensis enters a phagosome that acquires limited amounts of lysosome-associated membrane glycoproteins and does not acquire cathepsin d or markers of secondary lysosomes. with additional time after uptake, f. tularensis disrupts its phagosomal membrane and escapes into the cytoplasm. to assess the role of phagosome acidification in phagosome escape, we followed acidification using the vital stain lysotracker red and acquisition of the proton vacuolar atpase (vatp ... | 2009 | 19237528 |
| molecular epidemiology of francisella tularensis in the united states. | in the united states, tularemia is caused by francisella tularensis subsps. tularensis (type a) and holarctica (type b). molecular subtyping has further divided type a into 2 subpopulations, a1 and a2. significant mortality differences were previously identified between human infections caused by a1 (14%), a2 (0%) and type b (7%). to verify these findings and to further define differences among genotypes, we performed a large-scale molecular epidemiologic analysis of f. tularensis isolates from ... | 2009 | 19245342 |
| nonrandom distribution of vector ticks (dermacentor variabilis) infected by francisella tularensis. | the island of martha's vineyard, massachusetts, is the site of a sustained outbreak of tularemia due to francisella tularensis tularensis. dog ticks, dermacentor variabilis, appear to be critical in the perpetuation of the agent there. tularemia has long been characterized as an agent of natural focality, stably persisting in characteristic sites of transmission, but this suggestion has never been rigorously tested. accordingly, we sought to identify a natural focus of transmission of the agent ... | 2009 | 19247435 |
| the impact of chemokine receptor cx3cr1 deficiency during respiratory infections with mycobacterium tuberculosis or francisella tularensis. | recruitment of immune cells to infection sites is a critical component of the host response to pathogens. this process is facilitated partly through interactions of chemokines with cognate receptors. here, we examine the importance of fractalkine (cx3cl1) receptor, cx3cr1, which regulates function and trafficking of macrophages and dendritic cells, in the host's ability to control respiratory infections with mycobacterium tuberculosis or francisella tularensis. following low-dose aerosol challen ... | 2009 | 19250281 |
| tularaemia of middle ear with suppurative lymphadenopathy and retropharyngeal abscess. | we report an extremely rare case of otitis media due to francisella tularensis, complicated by multiple suppurative cervical lesions and a lasting conductive hearing loss. | 2009 | 19250590 |
| antigen-specific b-1a antibodies induced by francisella tularensis lps provide long-term protection against f. tularensis lvs challenge. | francisella tularensis (ft), a gram-negative intracellular bacterium, is the etiologic agent of tularemia. infection of mice with <10 ft live vaccine strain (ft lvs) organisms i.p. causes a lethal infection that resembles human tularemia. here, we show that immunization with as little as 0.1 ng ft lvs lipopolysaccharide (ft-lps), but not ft lipid a, generates a rapid antibody response that protects wild-type (wt) mice against lethal ft lvs challenge. protection is not induced in ft-lps-immunized ... | 2009 | 19251656 |
| phylogeography of francisella tularensis: global expansion of a highly fit clone. | francisella tularensis contains several highly pathogenic subspecies, including francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. the phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (snp) analysis, high-density microarray snp genotyping, and real-time-pcr-based canonical snp (cansnp) assays. almost 30,000 snps were identified among 13 whole genomes for phylogenetic analysis ... | 2009 | 19251856 |
| expression, purification and crystallization of class c acid phosphatases from francisella tularensis and pasteurella multocida. | class c nonspecific acid phosphatases are bacterial enzymes that are secreted across the cytoplasmic membrane and hydrolyze a variety of phosphomonoesters at acidic ph. these enzymes are of interest for the development of improved vaccines and clinical diagnostic methods. in one case, the category a pathogen francisella tularensis, the class c phosphatase plays a role in bacterial fitness. here, the cloning, expression, purification and crystallization methods for the class c acid phosphatases f ... | 2009 | 19255471 |
| comparison of antibody responses in atlantic cod (gadus morhua l.) to vibrio anguillarum, aeromonas salmonicida and francisella sp. | bacterial diseases such as vibriosis, atypical furunculosis and francisellosis, are registered as an increasing problem in cod farming in norway. in order to develop efficient vaccines against diseases it is of interest to investigate if the cod immune system differentiates between various serotypes of vibrio anguillarum and variants of aeromonas salmonicida associated with the diseases by raising specific antibody responses. cod of the same origin were shown to raise significant responses to v. ... | 2009 | 19084603 |
| functional expression of francisella tularensis fabh and fabi, potential antibacterial targets. | francisella tularensis is an extremely infectious airborne pathogen that has long been considered as a potential biological weapon. enzymes of fatty acid synthesis (fas) pathway are attractive targets for the development of new antibacterial agents because of differences between the biosynthesis pathways of bacteria and mammals. we report here the first expression of three functional enzymes in f. tularensis fas-ii pathway: fabh (3-oxoacyl-acyl carrier protein synthase iii) which initiates elong ... | 2009 | 19095065 |
| does the trojan horse have an achilles' heel? | 2009 | 19118310 | |
| re-emergence of tularemia in turkey. | four tularemia epidemics were reported from three different regions of turkey between 1936 and 1953. after a long interval, a new tularemia epidemic was reported from the area around bursa in the northwestern part of turkey in 1988. following this first epidemic in bursa, small epidemics occurred in areas around bursa between 1988 and 2002. other tularemia epidemics in different regions of turkey were reported between 1988 and 2005. almost all of the cases involved the oropharyngeal form of the ... | 2009 | 19119037 |
| influence of nutrient status and grazing pressure on the fate of francisella tularensis in lake water. | the natural reservoir of francisella tularensis, the causative agent of tularaemia, is yet to be identified. we investigated the possibility that francisella persists in natural aquatic ecosystems between outbreaks. it was hypothesized that nutrient-rich environments, with strong protozoan predation, favour the occurrence of the tularaemia bacterium. to investigate the differences in adaptation to aquatic environments of the species and subspecies of francisella, we screened 23 strains for their ... | 2009 | 19120459 |
| recombinant attenuated listeria monocytogenes vaccine expressing francisella tularensis iglc induces protection in mice against aerosolized type a f. tularensis. | fransicella tularensis, the causative agent of tularemia, is in the top category (category a) of potential agents of bioterrorism. to develop a safer vaccine against aerosolized f. tularensis, we have employed an attenuated listeria monocytogenes, which shares with f. tularensis an intracellular and extraphagosomal lifestyle, as a delivery vehicle for f. tularensis antigens. we constructed recombinant l. monocytogenes (rlm) vaccines stably expressing seven f. tularensis proteins including iglc ( ... | 2009 | 19126421 |
| a sensitive liquid chromatography/mass spectrometry-based assay for quantitation of amino-containing moieties in lipid a. | a novel sensitive liquid chromatography/mass spectrometry-based assay was developed for the quantitation of aminosugars, including 2-amino-2-deoxyglucose (glucosamine, glcn), 2-amino-2-deoxygalactose (galactosamine, galn), and 4-amino-4-deoxyarabinose (aminoarabinose, aran), and for ethanolamine (etn), present in lipid a. this assay enables the identification and quantitation of all amino-containing moieties present in lipopolysaccharide or lipid a from a single sample. the method was applied to ... | 2009 | 19130491 |
| improved shuttle vectors for francisella tularensis genetics. | we previously described the construction and characterization of escherichia coli-francisella tularensis shuttle vectors, derived from the cryptic francisella plasmid pfnl10, for the genetic manipulation of f. tularensis ssp. tularensis. we now report further characterization of the biology of these shuttle vectors and the development of a new generation of francisella plasmids. we show that the addition of orf3 from pfnl10 can convert an unstable shuttle vector into a stable one, and that this ... | 2009 | 19067747 |
| francisella tularensis regulates autophagy-related host cell signaling pathways. | the gram-negative intracellular pathogen francisella tularensis is known for its ability to dampen host immune responses. we recently performed a microarray analysis comparing human monocyte responses to the highly virulent f. tularensis tularensis schu s4 strain (f.t.) versus the less virulent f. tularensis novicida (f.n.).(1) many groups of genes were affected, including those involved with autophagy and with the regulation of autophagy. here, we discuss the implications in the context of fran ... | 2009 | 19029814 |
| host immune response and acute disease in a zebrafish model of francisella pathogenesis. | members of the bacterial genus francisella are highly virulent and infectious pathogens. new models to study francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. we took advantage of the recent discovery of a novel species of francisella to establish a zebrafish/francisella comparative model of pathogenesis and host immune response. adult zebrafish were susceptib ... | 2009 | 19047404 |
| inferring genomic flux in bacteria. | acquisition and loss of genetic material are essential forces in bacterial microevolution. they have been repeatedly linked with adaptation of lineages to new lifestyles, and in particular, pathogenicity. comparative genomics has the potential to elucidate this genetic flux, but there are many methodological challenges involved in inferring evolutionary events from collections of genome sequences. here we describe a model-based method for using whole-genome sequences to infer the patterns of gen ... | 2009 | 19015321 |
| an optimized, multiplexed multi-locus variable-number tandem repeat analysis system for genotyping francisella tularensis. | we present a truncated, optimized, multiplexed multiple-locus variable-number tandem repeat analysis system for the molecular subtyping of francisella tularensis that reduces time and cost requirements while retaining high discriminatory power. | 2009 | 19018964 |
| cellular and humoral immunity are synergistic in protection against types a and b francisella tularensis. | herein we report studies with a novel combination vaccine that, when administered to mice, conferred protection against highly virulent strains of francisella tularensis by stimulating both arms of the immune system. our earlier studies with ft.lvs::wbta, an o-polysaccharide (ops)-negative mutant derived from the available live vaccine strain of f. tularensis (ft.lvs), elucidated the role of antibodies to the ops - a key virulence determinant - in protection against virulent type a organisms. ho ... | 2009 | 19022323 |
| discovery of new biosynthetic pathways: the lipid a story. | the outer monolayer of the outer membrane of gram-negative bacteria consists of the lipid a component of lipopolysaccharide (lps), a glucosamine-based saccharolipid that is assembled on the inner surface of the inner membrane. the first six enzymes of the lipid a pathway are required for bacterial growth and are excellent targets for the development of new antibiotics. following assembly, the abc transporter msba flips nascent lps to the periplasmic side of the inner membrane, whereupon addition ... | 2009 | 18974037 |
| direct and indirect impairment of human dendritic cell function by virulent francisella tularensis schu s4. | the gram-negative, facultative intracellular bacterium francisella tularensis causes acute, lethal pneumonic disease following infection with only 10 cfu. the mechanisms used by the bacterium to accomplish this in humans are unknown. here, we demonstrate that virulent, type a f. tularensis strain schu s4 efficiently infects and replicates in human myeloid dendritic cells (dcs). despite exponential replication over time, schu s4 failed to stimulate transforming growth factor beta, interleukin-10 ... | 2009 | 18981246 |
| identification of an essential francisella tularensis subsp. tularensis virulence factor. | francisella tularensis, the highly virulent etiologic agent of tularemia, is a low-dose intracellular pathogen that is able to escape from the phagosome and replicate in the cytosol. although there has been progress in identifying loci involved in the pathogenicity of this organism, analysis of the genome sequence has revealed few obvious virulence factors. we previously reported isolation of an f. tularensis subsp. tularensis strain schu s4 transposon insertion mutant with a mutation in a predi ... | 2009 | 18981253 |
| nk cells activated in vivo by bacterial dna control the intracellular growth of francisella tularensis lvs. | we demonstrated previously that mice treated with bacterial or oligonucleotide dna containing unmethylated cpg motifs are transiently protected against lethal parenteral challenge with the intracellular bacterium francisella tularensis live vaccine strain (lvs). here we explore the cellular basis of this protection. wild-type mice that were treated with cpg oligonucleotide dna and challenged with a lethal dose of lvs survived, while mice lacking tlr9 did not. in vitro, treatment of lvs-infected ... | 2009 | 18992838 |
| francisella inhibits stat1-mediated signaling in macrophages and prevents activation of antigen-specific t cells. | signal transducer and activator of transcription-1 (stat1) signaling mediate most biological functions of ifnalpha, ifnbeta and ifngamma although recent studies indicate that ifngamma can alter expression of several genes via a stat1-independent pathway. stat1 is critical for immunity against a variety of intracellular pathogens and some studies show that pathogens evade host immunity by interfering with stat1 signaling. here, we have investigated the role of stat1 in host defense against pulmon ... | 2009 | 19001470 |
| iron transport in francisella in the absence of a recognizable tonb protein still requires energy generated by the proton motive force. | the mechanism of iron transport in francisella is still a puzzle since none of the sequenced francisella strains appears to encode a tonb protein, the energy transducer of the proton motive force necessary to act on the bacterial outer membrane siderophore receptor to allow the internalization of iron. in this work we demonstrate using kinetic experiments of radioactive fe(3+) utilization, that iron uptake in francisella novicida, although with no recognizable tonb protein, is indeed dependent o ... | 2009 | 18946633 |
| 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. | 2009 | 18950590 |
| electrical microarrays for highly sensitive detection of multiplex pcr products from biological agents. | for the sensitive detection of amplicons derived from diagnostic pcr, a novel electrical low-density microarray is applied and compared to state-of-the-art quantitative real-time pcr. the principle of the electrochemical method and the effective use for analysis are described. interdigitated array gold electrodes (ida-e) embedded into a silicon chip are the core technology of the fully automated compact biosensor system, basing on enzyme coupled electrochemical detection. the biointerface is bui ... | 2009 | 18954971 |
| genome-wide screen in francisella novicida for genes required for pulmonary and systemic infection in mice. | francisella tularensis is a gram-negative, highly infectious, aerosolizable facultative intracellular pathogen that causes the potentially life-threatening disease tularemia. to date there is no approved vaccine available, and little is known about the molecular mechanisms important for infection, survival, and dissemination at different times of infection. we report the first whole-genome screen using an inhalation mouse model to monitor infection in the lung and dissemination to the liver and ... | 2009 | 18955478 |
| glycogen synthase kinase-3beta (gsk3beta) inhibition suppresses the inflammatory response to francisella infection and protects against tularemia in mice. | francisella tularensis, the causative agent of tularemia, is currently considered a category a bioterrorism agent due to its high virulence. infection with f. tularensis results in an inflammatory response that plays an important role in the pathogenesis of the disease; however, the cellular mechanisms regulating this response are poorly understood. glycogen synthase kinase-3beta (gsk3beta) is a serine/threonine protein kinase that has recently emerged as a key regulatory switch in the modulatio ... | 2009 | 18929413 |
| characterization and genotyping of strains of francisella tularensis isolated in bulgaria. | a tularaemia focus was detected in 1998 in bulgaria, in an area where tularaemia had never been reported. the properties of francisella tularensis subsp. holarctica strains isolated from 1998 to 2005 were studied. the strains showed heterogeneity, based on acid production from glycerol and erythromycin susceptibility. genotyping by analysis of seven loci containing variable-number tandem repeats showed four genotypes among eight strains. | 2009 | 19074656 |
| an outbreak of oropharyngeal tularaemia linked to natural spring water. | a tularaemia outbreak was investigated involving 188 suspected cases in the kocaeli region of turkey between december 2004 and april 2005. a case-control study comprising 135 laboratory-confirmed cases and 55 controls was undertaken to identify risk factors for the development of the outbreak and to evaluate laboratory diagnostic methods. tularaemia was confirmed by a microagglutination test (mat) titre of >or=1 : 160 in 90 of the patients. in mat-negative sera, 23/44 (52 %) were positive by eli ... | 2009 | 19074661 |
| [prevalence of epidemic outbreak of tularemia in the hospital universitario río hortega (spain) in the year 2007]. | this present research study presents the analytic results of an outbreak of tularemia (francisella tularensis) that occurred in the northwest areas of castilla y león in northern spain in late june 2007. | 2009 | 19709538 |
| [tularemia as a pediatric problem]. | the diagnosis of tularemia is based on the clinical picture, and epidemics are brief and local. in children, recognition of tularaemia may be challenging, as an inflamed mosquito bite mark may be covered under the hair, and lymph node enlargement is associated with other febrile diseases as well. half of the children have vesicopapular skin changes. fluoroqinolones and aminoglycosides area effective against francisella tularensis in vitro, and the efficacy of treatment seems to be the better the ... | 2009 | 19711573 |
| identification of francisella tularensis live vaccine strain cuzn superoxide dismutase as critical for resistance to extracellularly generated reactive oxygen species. | francisella tularensis is an intracellular pathogen whose survival is in part dependent on its ability to resist the microbicidal activity of host-generated reactive oxygen species (ros) and reactive nitrogen species (rns). in numerous bacterial pathogens, cuzn-containing superoxide dismutases (sodc) are important virulence factors, localizing to the periplasm to offer protection from host-derived superoxide radicals (o(2)(-)). in the present study, mutants of f. tularensis live vaccine strain ( ... | 2009 | 19684141 |
| real-time pcr strategy and detection of bacterial agents of lymphadenitis. | the aim of this study was to compare 16 s rrna gene amplification and sequencing with a systematic real-time pcr assay screening strategy that includes all common known pathogens recovered from lymph node biopsy specimens. lymph node biopsy samples sent to our laboratory from january 2007 to december 2008 were tested in the study. lymph nodes were screened for the presence of any bacteria by pcr amplification and sequencing targeting the 16 s rrna gene and also by a specific real-time pcr strate ... | 2009 | 19685089 |
| [tularemia]. | tularemia is a zoonotic disease caused by francisella tularensis. the etiological agent is transmitted to man by direct contact with infected animals, air, water or contaminated food, or through hematophagous vectors. in portugal, in 1998, after an outbreak in spain, the direcção geral de saúde issued a warning, alerting the clinicians to the possibility of the disease spreading throughout the national territory. in this work, an epidemiological review of tularemia is made in order to contribute ... | 2009 | 19686629 |
| francisella tularensis induces ubiquitin-dependent major histocompatibility complex class ii degradation in activated macrophages. | the intracellular bacterium francisella tularensis survives and replicates within macrophages, ultimately killing the host cell. resolution of infection requires the development of adaptive immunity through presentation of f. tularensis antigens to cd4+ and cd8+ t cells. we have previously established that f. tularensis induces macrophage prostaglandin e2 (pge2) production, leading to skewed t-cell responses. pge2 can also downregulate macrophage major histocompatibility complex (mhc) class ii e ... | 2009 | 19703975 |
| francisella tularensis induces extensive caspase-3 activation and apoptotic cell death in the tissues of infected mice. | although francisella tularensis subsp. tularensis is known to cause extensive tissue necrosis, the pathogenesis of tissue injury has not been elucidated. to characterize cell death in tularemia, c57bl/6 mice were challenged by the intranasal route with type a f. tularensis, and the pathological changes in infected tissues were characterized over the next 4 days. at 3 days postinfection, well-organized inflammatory infiltrates developed in the spleen and liver following the spread of infection fr ... | 2009 | 19703976 |
| cgug: in silico proteome and genome parsing tool for the determination of "core" and unique genes in the analysis of genomes up to ca. 1.9 mb. | viruses and small-genome bacteria (~2 megabases and smaller) comprise a considerable population in the biosphere and are of interest to many researchers. these genomes are now sequenced at an unprecedented rate and require complementary computational tools to analyze. "coregenesuniquegenes" (cgug) is an in silico genome data mining tool that determines a "core" set of genes from two to five organisms with genomes in this size range. core and unique genes may reflect similar niches and needs, and ... | 2009 | 19706165 |
| pharmacological exploitation of an off-target antibacterial effect of the cyclooxygenase-2 inhibitor celecoxib against francisella tularensis. | francisella tularensis, a bacterium which causes tularemia in humans, is classified as a cdc category a bioterrorism agent. in this study, we demonstrate that celecoxib, an anti-inflammatory cyclooxygenase-2 inhibitor in clinical use, exhibits activity against a type a strain of f. tularensis (schu s4), the live vaccine strain of f. tularensis (a type b strain), and f. novicida ("f. tularensis subsp. novicida") directly in growth medium. this bacterial killing, however, was not noted with rofeco ... | 2009 | 19398640 |
| lethal pulmonary infection with francisella novicida is associated with severe sepsis. | the bacterial or host determinants of lethality associated with respiratory francisella infections are currently unknown. no exo- or endotoxins that contribute to the severity of this disease have been identified. however, a deregulated host immune response upon infection is characterized by an initial 36- to 48-h delay followed by a rapid and excessive inflammatory response prior to death at 72-120 h. here, we extend these findings by comparing host immune responses between sublethal and lethal ... | 2009 | 19401387 |
| generalized tularemia in a vervet monkey (chlorocebus aethiops) and a patas monkey (erythrocebus patas) in a zoo. | generalized tularemia was diagnosed in a vervet monkey (chlorocebus aethiops) and a patas monkey (erythrocebus patas), both of which died suddenly in the szeged zoo, szeged, hungary. macroscopic lesions in each animal included disseminated, grayish-white foci in the lungs, lymph nodes, spleen, liver, and kidney. all focal lesions were characterized microscopically as purulent to pyogranulomatous to granulomatous inflammation with necrosis. francisella tularensis subsp. holarctica strains were is ... | 2009 | 19407096 |
| the role of complement opsonization in interactions between f. tularensis subsp. novicida and human neutrophils. | the remarkable infectiousness of francisella tularensis suggests that the bacterium efficiently evades innate immune responses that typically protect the host during its continuous exposure to environmental and commensal microbes. in our studies of the innate immune response to f. tularensis, we have observed that, unlike the live vaccine strain (lvs) of f. tularensis subsp. holarctica, f. tularensis subsp. novicida u112 opsonized in pooled human serum activated the nadph oxidase when incubated ... | 2009 | 19409509 |
| ticks and tick-borne pathogens and putative symbionts of black bears (ursus americanus floridanus) from georgia and florida. | ticks were collected from 38 black bears (ursus americanus floridanus) from northwestern florida (n = 18) from 2003 to 2005 and southern georgia (n = 20) in 2006. five species (amblyomma americanum, a. maculatum, dermacentor variabilis, ixodes scapularis, and i. affinis) were collected from florida bears, and 4 species (a. americanum, a. maculatum, d. variabilis, i. scapularis) were collected from bears in georgia. ixodes scapularis was the most frequently collected tick, followed by d. variabil ... | 2009 | 19413369 |
| direct isolation of francisella spp. from environmental samples. | to develop a selective medium for isolation of f. tularensis, f. novicida and f. philomiragia from environmental samples. | 2009 | 19413814 |
| itraq quantitative analysis of francisella tularensis ssp. holarctica live vaccine strain and francisella tularensis ssp. tularensis schu s4 response to different temperatures and stationary phases of growth. | proteomics has been shown to significantly contribute to the investigation of the pathogenicity of the extremely infectious bacteria francisella tularensis. in this study, the authors employed itraq quantitative proteomic analysis in order to monitor alterations in proteomes of f. tularensis ssp. holarctica live vaccine strain and f. tularensis ssp. tularensis schu s4 associated with the cultivation at different temperatures or in the stationary phase. correlated production of the identified pro ... | 2009 | 19415661 |
| specific recognition of the major capsid protein of acanthamoeba polyphaga mimivirus by sera of patients infected by francisella tularensis. | francisella tularensis, a gram-negative cocobacillus responsible for tularemia, especially severe pneumonia, is a facultative intracellular bacterium classified as a biological agent of category a. acanthamoeba polyphaga mimivirus (apm) is a recently discovered giant virus suspected to be an agent of both community- and hospital-acquired pneumonia. during specificity testing of antibody to apm detection, it was observed that nearly all patients infected by f. tularensis had elevated antibody tit ... | 2009 | 19538509 |
| [prolonged course of tick-borne ulceroglandular tularemia in a 20-year-old patient in germany--case report and review of the literature]. | a 20-year-old female patient presented with painful axillary lymphadenopathy. she reported a tick bite five months ago in her right hand followed by fever, chills and regional lymphadenopathy. empiric antibiotic treatment with doxycyclin and ciprofloxacin had led to defervescence but no change in painful lymph node swellings. surgical removal of a cubital lymph node had already been performed three months after the tick bite. | 2009 | 19551605 |
| tick-borne zoonotic bacteria in ticks collected from central spain. | the prevalence of tick-borne and related bacteria infecting adult ticks in central spain was assessed by molecular methods. six areas were sampled monthly during a 2-year longitudinal study. a total of 1,038 questing and 442 feeding ticks, belonging to eight different species, were tested. the most abundant species were hyalomma lusitanicum (54% of captures), followed by dermacentor marginatus (23%) and rhipicephalus sanguineus (10%). four human pathogens, including seven rickettsia species, ana ... | 2009 | 19556569 |
| tularemia induces different biochemical responses in balb/c mice and common voles. | both balb/c mice and common voles (microtus arvalis) are considered highly susceptible to tularemia. however, the common vole is reported to harbour francisella tularensis in european habitats as well as to survive longer with chronic shedding of the bacterium. the purpose of the present study was to compare the response of these two rodents to a wild francisella tularensis subsp. holarctica strain infection. | 2009 | 19558687 |
| safety, reactogenicity and immunogenicity of francisella tularensis live vaccine strain in humans. | we evaluated the safety, reactogenicity and immunogenicity of escalating doses of a new francisella tularensis live vaccine strain (lvs) lot by scarification (scar) or subcutaneously (sq) in humans. subjects (n=10/group) received one dose of lvs via scar at 10(5),10(7) or 10(9)cfu/ml or sq at 10(2), 10(3),10(4) or 10(5)cfu/ml; 14 subjects received placebo. all doses/routes were well tolerated. when compared to placebo, vaccination with 10(7) scar and 10(9) scar resulted in significantly higher s ... | 2009 | 19567246 |
| tularemia type a in captive bornean orangutans (pongo pygmaeus pygmaeus). | in 2003, tularemia was suspected to be the cause of severe illness in two orangutans (pongo pygmaeus pygmaeus) and the cause of death in a third orangutan at an urban zoo. the two sick orangutans were treated two times under chemical immobilization with i.v. doxycycline, fluids, and antipyretic drugs, followed by a sustained course of oral doxycycline. the rest of the orangutan group was treated prophylactically with oral doxycycline. postmortem diagnosis was obtained via immunohistochemistry an ... | 2009 | 19569471 |
| [experimental verification of a model of complement-dependent immune lysis of liposomes]. | the quantitative dependences of the immune complement-dependent lysis of a monodisperse suspension of 200-nm liposomes whose membrane was sensitized by monovalent hapten (2,4-dnp-epsilon-caproyl-dppe) or a polyvalent antigen (lps from f. tularensis) on the initial concentration of specific antibodies (igg) to hapten and the antigen have been investigated. the quantity of antibodies binding sites on the surface of liposome was evaluated. the difference between the complement-dependent immune lysi ... | 2009 | 19569506 |
| familial tularaemia. | tularaemia is a zoonotic disease caused by francisella tularensis . in this report, we have presented an early stage case of tularemia with fever and pharyngitis and two cases from the same non-endemic region with typical lymphadenitis. all three patients were treated with non-specific medications in healthcare centres, the treatment being directed towards symptoms resembling those of upper respiratory tract infections. however, there was no regression in their complaints. because the first case ... | 2009 | 19584516 |
| comparative antimicrobial activity of granulysin against bacterial biothreat agents. | granulysin is a cationic protein produced by human t cells and natural killer cells that can kill bacterial pathogens through disruption of microbial membrane integrity. herein we demonstrate antimicrobial activity of the granulysin peptide derived from the active site against bacillus anthracis, yersinia pestis, francisella tularensis, and burkholderia mallei, and show pathogen-specific differences in granulysin peptide effects. the susceptibility of y. pestis to granulysin is temperature depen ... | 2009 | 19587798 |
| tularemia - missouri, 2000-2007. | tularemia is an uncommon but potentially fatal zoonotic disease caused by the gram-negative coccobacillus francisella tularensis. approximately 40% of all tularemia cases reported to cdc each year occur in arkansas, oklahoma, and missouri. to define the epidemiologic and clinical features of tularemia in missouri, the missouri department of health and senior services (mdhss) analyzed surveillance data and conducted a retrospective clinical chart review of cases that occurred during 2000--2007. t ... | 2009 | 19609248 |
| development of a macrophage cell culture method to isolate and enrich francisella tularensis from food matrices for subsequent detection by real-time pcr. | francisella tularensis is a gram-negative bacterium that can cause gastrointestinal or oropharyngeal tularemia in humans from ingestion of contaminated food or water. despite the potential for accidental or intentional contamination of foods with f. tularensis, there are no techniques currently available to detect this organism in specific food matrices. in this study, a macrophage cell culture system is combined with real-time pcr to identify f. tularensis in food matrices. the method utilizes ... | 2009 | 19610325 |
| description of two new plasmids isolated from francisella philomiragia strains and construction of shuttle vectors for the study of francisella tularensis. | francisella tularensis is the causative agent of tularemia, a zoonotic disease often transmitted to humans by infected animals. the lack of useful specific genetic tools has long hampered the study of f. tularensis subspecies. we identified and characterized two new plasmids, pf242 and pf243, isolated from francisella philomiragia strains atcc 25016 and atcc 25017, respectively. sequence analysis revealed that pf242 and pf243 are closely related to pc194 and pfnl10 plasmids, respectively. two ge ... | 2009 | 19615403 |
| epitope-based vaccination against pneumonic tularemia. | francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacterial pathogens known. no vaccine is currently approved for public use. previously, we identified epitopes recognized specifically by t cells obtained from individuals following infection with f. tularensis. here, we report that a subunit vaccine constructed based upon these epitopes elicited protective immunity in "humanized" hla class ii (drb1*0401) transgenic mice. vaccinated mice challenged intratra ... | 2009 | 19616492 |
| tam receptors are dispensable in the phagocytosis and killing of bacteria. | many receptors that are employed for the engulfment of apoptotic cells are also used for the recognition and phagocytosis of bacteria. tyro3, axl, and mertk (tam) are important in the phagocytosis of apoptotic cells by macrophages. animals lacking these receptors are hypersensitive to bacterial products. in this report, we examine whether the tam receptors are involved in the phagocytosis of bacteria. we found that macrophages lacking mertk, axl, tyro3 or all three receptors were equally efficie ... | 2009 | 19625016 |
| metapopulation structure for perpetuation of francisella tularensis tularensis. | outbreaks of type a tularemia due to francisella tularensis tularensis are typically sporadic and unstable, greatly hindering identification of the determinants of perpetuation and human risk. martha's vineyard, massachusetts has experienced an outbreak of type a tularemia which has persisted for 9 years. this unique situation has allowed us to conduct long-term eco-epidemiologic studies there. our hypothesis is that the agent of type a tularemia is perpetuated as a metapopulation, with many sma ... | 2009 | 19627585 |
| vaccination with an attenuated strain of francisella novicida prevents t-cell depletion and protects mice infected with the wild-type strain from severe sepsis. | francisella tularensis is the causative agent of zoonotic tularemia, a severe pneumonia in humans, and francisella novicida causes a similarly severe tularemia in mice upon inhalation. the correlates of protective immunity, as well as the virulence mechanisms of this deadly pathogen, are not well understood. in the present study, we compared the host immune responses of lethally infected and vaccinated mice to highlight the host determinants of protection from this disease. intranasal infection ... | 2009 | 19635830 |
| evidence for the presence of francisella and spotted fever group rickettsia dna in the tick amblyomma fimbriatum (acari: ixodidae), northern territory, australia. | ticks (n = 252) were collected from five wild-caught reptile species during routine trapping in the djukbinj national park and fogg dam reserve, northern territory, australia. pooling of ticks (one to four ticks per pool), according to sex or host animal, resulted in 187 samples used for screening for the presence of rickettsia species via molecular methods. rickettsia dna was detected via the amplification of the glta, ompa, and ompb genes in 57 (34%) of the 187 tick samples, all of which conta ... | 2009 | 19645299 |
| vaccination with a defined francisella tularensis subsp. novicida pathogenicity island mutant (deltaiglb) induces protective immunity against homotypic and heterotypic challenge. | francisella tularensis, an intracellular gram-negative bacterium, is the causative agent of tularemia and a potential bioweapon. currently, there is no licensed vaccine against this organism. we have characterized the efficacy of a defined f. tularensis subsp. novicida mutant (deltaiglb) as a live attenuated vaccine against pneumonic tularemia. replication of the iglb mutant (kkf235) in murine macrophages was significantly lower than the wild type novicida strain u112, and exhibited an ld(50) gr ... | 2009 | 19651173 |
| the 58-kilodalton major virulence factor of francisella tularensis is required for efficient utilization of iron. | we investigated the role of the 58-kda ftt0918 protein in the iron metabolism of francisella tularensis. the phenotypes of schu s4, a prototypic strain of f. tularensis subsp. tularensis, and the delta ftt0918 and delta fsla isogenic mutants were analyzed. the gene product missing in the delta fsla mutant is responsible for synthesis of a siderophore. when grown in broth with various iron concentrations, the two deletion mutants generally reached lower maximal densities than schu s4. the delta f ... | 2009 | 19651867 |
| loops and networks in control of francisella tularensis virulence. | francisella tularensis is a highly infectious, gram-negative bacterium responsible for the disease tularemia in a broad variety of animals, including humans. f. tularensis intracellular multiplication occurs mainly in macrophages. however, f. tularensis is able to infect many other cell types, including other phagocytic (dendritic cells, polymorphonuclear leukocytes) and nonphagocytic (alveolar epithelial cells, hepatocytes, endothelial cells and fibroblasts) cells. the ability of professional p ... | 2009 | 19659427 |
| pathology of inhalational francisella tularensis spp. tularensis schu s4 infection in african green monkeys (chlorocebus aethiops). | tularemia, caused by francisella tularensis, is a sporadic zoonotic disease with the potential to be an agent of biowarfare or bioterrorism. we describe here the gross, histologic, immunohistochemical, and ultrastructural findings in a group of 5 african green monkeys (agms) that received an average inhaled dose of 729 colony-forming units of f. tularensis and died or were euthanatized between days 7 and 11 post infection. clinical changes were evident by 48 hours post infection, and key physiol ... | 2009 | 19276059 |
| single-copy chromosomal integration systems for francisella tularensis. | francisella tularensis is a fastidious gram-negative bacterium responsible for the zoonotic disease tularemia. investigation of the biology and molecular pathogenesis of f. tularensis has been limited by the difficulties in manipulating such a highly pathogenic organism and by a lack of genetic tools. however, recent advances have substantially improved the ability of researchers to genetically manipulate this organism. to expand the molecular toolbox we have developed two systems to stably inte ... | 2009 | 19332817 |
| cervical tularaemia in a non-endemic area. | tularemia is a zoonotic disease caused by francisella tularensis. the microorganism is transmitted to humans by contact with, or ingestion of, infected animal tissues, by insect bites, consumption of contaminated food or water, or from inhalation of aerolized bacteria. in this report we describe a case of tularemia presenting with multiple cervical lymphadenitis in asturias (spain). final diagnosis was established based on a serological test. the patient was successfully managed with surgery and ... | 2009 | 19333186 |
| establishment of lethal inhalational infection with francisella tularensis (tularaemia) in the common marmoset (callithrix jacchus). | susceptibility and lethality studies of inhalational tularaemia were undertaken using the common marmoset (callithrix jacchus) to determine its suitability as a non-human primate model. pairs of marmosets were exposed to varying challenge doses of francisella tularensis by the airborne route and monitored for up to 14 days postchallenge (p.c.). lethal infection was achieved following a retained dose of less than 10 bacterial colony-forming units (cfu). however, precise ld(50) determination was n ... | 2009 | 19335549 |
| virulence and pathogenicity of francisella philomiragia subsp. noatunensis for atlantic cod, gadus morhua l., and laboratory mice. | 2009 | 19335614 | |
| differential requirements for protection against mucosal challenge with francisella tularensis in the presence versus absence of cholera toxin b and inactivated f. tularensis. | francisella tularensis is a category a biothreat agent for which there is no approved vaccine and the correlates of protection are not well understood. in particular, the relationship between the humoral and cellular immune response to f. tularensis and the relative importance of each in protection is controversial. yet, understanding this relationship will be crucial to the development of an effective vaccine against this organism. we demonstrate, for the first time, a differential requirement ... | 2009 | 19342669 |
| an 8-year-old boy with fever, axillary ulcerative lesion, and altered mental status. | 2009 | 19344255 | |
| francisella tularensis directly interacts with the endothelium and recruits neutrophils with a blunted inflammatory phenotype. | francisella tularensis, the causative agent of tularemia, is a highly virulent organism, especially when exposure occurs by inhalation. recent data suggest that francisella interacts directly with alveolar epithelial cells. although f. tularensis causes septicemia and can live extracellularly in a murine infection model, there is little information about the role of the vascular endothelium in the host response. we hypothesized that f. tularensis would interact with pulmonary endothelial cells a ... | 2009 | 19346432 |
| identification of migr, a regulatory element of the francisella tularensis live vaccine strain iglabcd virulence operon required for normal replication and trafficking in macrophages. | francisella tularensis, the etiological agent of tularemia, is capable of infecting a wide range of animals and causes a severe, lethal disease in humans. the pathogen evades killing by cells of the innate immune system utilizing genes encoding a pathogenicity island, including iglabcd, and instead utilizes these cells as a niche for replication and dissemination to other organs within the host. regulators of the igl genes (e.g., mgla, sspa, fevr and pmra) have been identified, but environmental ... | 2009 | 19349423 |
| francisella-like endosymbiont dna and francisella tularensis virulence-related genes in brazilian ticks (acari: ixodidae). | ticks are vectors of a variety of pathogens, including francisella tularensis. bacteria in the genus francisella have been identified mostly in the northern hemisphere and include tick endosymbionts. francisella has never been described in brazil, where amblyomma spp. ticks are known as the vector of many bacterial zoonotic pathogens. in the present work, we have identified bacterial dna sequences with identity to francisella genes in amblyomma dubitatum neumann dermacentor nitens (neumann), and ... | 2009 | 19351090 |
| lethal pulmonary infection with francisella novicida causes depletion of alphabeta t cells from lungs. | respiratory francisella infections induce a delayed innate immune response followed by a severe sepsis like condition. in this study, mice infected intranasally with francisella novicida showed a depletion of alphabeta t cells in lungs while exhibiting large accumulations of other leukocytes correlating with disease severity. the depleted t cells were predominantly cd4(+). the alphabeta t cells in infected mice showed significantly higher levels of annexin v binding than those in mock control mi ... | 2009 | 19356746 |
| tularemic meningitis in the united states. | tularemia is a zoonotic disease caused by francisella tularensis. tularemia presents with various clinical illnesses, but meningitis is rare. | 2009 | 19364939 |
| characterization of rationally attenuated francisella tularensis vaccine strains that harbor deletions in the guaa and guab genes. | francisella tularensis, the etiologic agent of tularemia, can cause severe and fatal infection after inhalation of as few as 10 -- 100cfu. f. tularensis is a potential bioterrorism agent and, therefore, a priority for countermeasure development. vaccination with the live vaccine strain (lvs), developed from a type b strain, confers partial protection against aerosal exposure to the more virulent type a strains and provides proof of principle that a live attenuated vaccine strain may be efficacio ... | 2009 | 19368784 |
| life on the inside: the intracellular lifestyle of cytosolic bacteria. | bacterial pathogens exploit a huge range of niches within their hosts. many pathogens can invade non-phagocytic cells and survive within a membrane-bound compartment. however, only a small number of bacteria, including listeria monocytogenes, shigella flexneri, burkholderia pseudomallei, francisella tularensis and rickettsia spp., can gain access to and proliferate within the host cell cytosol. here, we discuss the mechanisms by which these cytosolic pathogens escape into the cytosol, obtain nut ... | 2009 | 19369949 |
| characterization of the pathogenicity island protein pdpa and its role in the virulence of francisella novicida. | francisella tularensis is a highly virulent, intracellular pathogen that causes the disease tularaemia. a research surrogate for f. tularensis is francisella novicida, which causes a tularaemia-like disease in mice, grows similarly in macrophages, and yet is unable to cause disease in humans. both francisella species contain a cluster of genes referred to as the francisella pathogenicity island (fpi). pathogenicity determinant protein a (pdpa), encoded by the pdpa gene, is located within the fpi ... | 2009 | 19372153 |
| a francisella novicida pdpa mutant exhibits limited intracellular replication and remains associated with the lysosomal marker lamp-1. | several genes contained in the francisella pathogenicity island (fpi) encode proteins needed for intracellular growth and virulence of francisella tularensis. the pdpa gene is the first cistron in the larger of the two operons found in the fpi. in this work we studied the intracellular growth phenotype of a francisella novicida mutant in the pdpa gene. the deltapdpa strain was capable of a small amount of intracellular replication but, unlike wild-type f. novicida, remained associated with the l ... | 2009 | 19372155 |
| intracellular biology and virulence determinants of francisella tularensis revealed by transcriptional profiling inside macrophages. | summary the highly infectious bacterium francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. here we have performed a global transcriptional profiling of the highly virulent f. tularensis ssp. tularensis schu s4 strain during its intracellular cycle within primary murine macrophages, to characterize its intracellular biology and identify pathogenic determinants based on their intracellular expression prof ... | 2009 | 19388904 |
| targeted gene disruption in francisella tularensis by group ii introns. | francisella tularensis is a highly infectious gram-negative bacterium that is the causative agent of tularemia. very little is known about the molecular mechanisms responsible for f. tularensis virulence, in part due to the paucity of genetic tools available for the study of f. tularensis. we have developed a gene knockout system for f. tularensis that utilizes retargeted mobile group ii introns, or "targetrons". these targetrons disrupt both single and duplicated target genes at high efficiency ... | 2009 | 19398003 |
| functional analyses of pilin-like proteins from francisella tularensis: complementation of type iv pilus phenotypes in neisseria gonorrhoeae. | accumulating evidence from a number of studies strongly suggests that proteins orthologous to those involved in type iv pili (tfp) assembly and function are required for francisella pathogenicity. however, the molecular mechanisms by which the components exert their influence on virulence remain poorly understood. owing to the conservation and promiscuity of tfp biogenesis machineries, expression of tfp pilins in heterologous species has been used successfully to analyse organelle structure-func ... | 2009 | 19423631 |
| identification of genes contributing to the virulence of francisella tularensis schu s4 in a mouse intradermal infection model. | francisella tularensis is a highly virulent human pathogen. the most virulent strains belong to subspecies tularensis and these strains cause a sometimes fatal disease. despite an intense recent research effort, there is very limited information available that explains the unique features of subspecies tularensis strains that distinguish them from other f. tularensis strains and that explain their high virulence. here we report the use of targeted mutagenesis to investigate the roles of various ... | 2009 | 19424499 |
| comparison of traditional and molecular analytical methods for detecting biological agents in raw and drinking water following ultrafiltration. | to compare the performance of traditional methods to quantitative polymerase chain reaction (qpcr) for detecting five biological agents in large-volume drinking-water samples concentrated by ultrafiltration (uf). | 2009 | 19426268 |
| pivotal role of the francisella tularensis heat-shock sigma factor rpoh. | francisella tularensis is a highly infectious pathogen that infects animals and humans to cause the disease tularemia. the primary targets of this bacterium are macrophages, in which it replicates in the cytoplasm after escaping the initial phagosomal compartment. the ability to replicate within macrophages relies on the tightly regulated expression of a series of genes. one of the most commonly used means of coordinating the regulation of multiple genes in bacteria consists of the association o ... | 2009 | 19443547 |
| [effect of serotonin and dopamine on growth of yersinia pestis and francisella tularensis strains]. | to study the effects of serotonin and dophamine on the growth of yersinia pestis and francisella tularensis strains as well as ability of monoamines to change susceptibility of experimental animals to plague infection. | 2009 | 19459486 |
| [development of a multiplex pcr-suspension array for simultaneous detection of five bioterrorism bacteria]. | to develop a rapid, high-throughput screening method of gene suspension array technique to simultaneously detect five bioterrorism bacteria: bacillus anthracis, francisella tularensis, yersinia pestis, brucella spp. and burkholderia pseudomallei. | 2009 | 19462919 |
| comparative genomic characterization of francisella tularensis strains belonging to low and high virulence subspecies. | tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. it is caused by infection by a gram-negative bacterium, francisella tularensis. in order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different francisella subspecies (subsp.): the f. tularensis sub ... | 2009 | 19478886 |