Publications

macrophage pro-inflammatory response to francisella novicida infection is regulated by ship.	francisella tularensis, a gram-negative facultative intracellular pathogen infecting principally macrophages and monocytes, is the etiological agent of tularemia. macrophage responses to f. tularensis infection include the production of pro-inflammatory cytokines such as interleukin (il)-12, which is critical for immunity against infection. molecular mechanisms regulating production of these inflammatory mediators are poorly understood. herein we report that the sh2 domain-containing inositol ph ...	2006	16848641
tularemia as a cause of fever in a squirrel monkey.	a 3-year-old female squirrel monkey (saimiri sciureus sciureus) was examined because of sudden onset of lethargy and fever.	2006	16842053
the bla2 beta-lactamase from the live-vaccine strain of francisella tularensis encodes a functional protein that is only active against penicillin-class beta-lactam antibiotics.	francisella tularensis ssp. tularensis is a category a select agent and the causal organism for the zoonotic disease tularemia. the vast majority of f. tularensis isolates are beta-lactamase-positive. beta-lactamase production is widely believed to be responsible for the inefficacy of beta-lactams in the treatment of tularemia. in this study, we report the cloning and characterization of the two chromosomally encoded f. tularensis ssp. holarctica live-vaccine strain (lvs) beta-lactamases. the tw ...	2006	16841206
epidemiologic and molecular analysis of human tularemia, united states, 1964-2004.	tularemia in the united states is caused by 2 subspecies of francisella tularensis, subspecies tularensis (type a) and subspecies holarctica (type b). we compared clinical and demographic features of human tularemia cases from 1964 to 2004 from 39 states in which an isolate was recovered and subtyped. our data indicate that type a and type b infections differ with respect to affected populations, anatomic site of isolation, and geographic distribution. molecular subtyping with pulsed-field gel e ...	2006	16836829
[vntr-genotyping of francisella tularensis strains isolated in the former ussr territory and some european countries during epizootics in 1988 - 1989].	retrospective vntr-analysis of 159 francisella tularensis subsp. holarctica strains isolated in december 1988 - february 1989 in former ussr and some european countries was carried out. analysis of heterogenic genotypes of strains allow to subdivide them into 30 groups of variants by individual genotypes, while cluster analysis--to subdivide them in 7 clusters with different number of compositions. the predominance of genotype c1 strains isolated on the rostov and archangelsk regions and the cri ...	2006	16830584
transcriptional profiling of the peripheral blood response during tularemia.	tularemia is a febrile disease caused by the highly contagious bacterium francisella tularensis. we undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of affymetrix microarrays comprising 14,500 genes. samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. in total, 265 genes were differentially expressed, 95 of which at more ...	2006	16826236
population structure of francisella tularensis.	we have sequenced fragments of five metabolic housekeeping genes and two genes encoding outer membrane proteins from 81 isolates of francisella tularensis, representing all four subspecies. phylogenetic clustering of gene sequences from f. tularensis subsp. tularensis and f. tularensis subsp. holarctica aligned well with subspecies affiliations. in contrast, f. tularensis subsp. novicida and f. tularensis subsp. mediasiatica were indicated to be phylogenetically incoherent taxa. incongruent gene ...	2006	16816208
differential infection of mononuclear phagocytes by francisella tularensis: role of the macrophage mannose receptor.	francisella tularensis (ft) is a gram-negative bacterium and the causative agent of tularemia. it is well established that this organism replicates inside macrophages, but we are only beginning to understand this interface at the molecular level. herein, we compared directly the ability of ft subspecies holarctica live-vaccine strain to infect freshly isolated human peripheral blood monocytes, monocyte-derived macrophages (mdm), and cells of the murine macrophage cell line j774a.1 (j774). we now ...	2006	16816147
identification of francisella tularensis genes affected by iron limitation.	cells of an attenuated live vaccine strain (lvs) of f. tularensis grown under iron-restricted conditions were found to contain increased quantities of several proteins relative to cells of this same strain grown under iron-replete conditions. mass spectrometric analysis identified two of these proteins as iglc and pdpb, both of which are encoded by genes located in a previously identified pathogenicity island in f. tularensis lvs. regions with homology to the consensus fur box sequence were loca ...	2006	16790797
identification, recombinant expression, immunolocalization in macrophages, and t-cell responsiveness of the major extracellular proteins of francisella tularensis.	a safer and more effective vaccine than the previously developed live attenuated vaccine is needed for combating francisella tularensis, a highly infectious bacterial pathogen. to search for potential candidates for inclusion in a new vaccine, we characterized the proteins present in the culture filtrates of a virulent recent clinical isolate and the attenuated live vaccine strain of f. tularensis using a proteomic approach. we identified a total of 12 proteins; among these, catalase-peroxidase ...	2006	16790773
immunoproteomic analysis of the murine antibody response to successful and failed immunization with live anti-francisella vaccines.	francisella tularensis subspecies tularensis is one of the most virulent of bacterial pathogens for humans. protective immunity against the pathogen can be induced in humans and some, but not all, mouse strains by vaccination with live, but not killed, vaccines. in mice, this protection is mediated predominantly by cd4+ and cd8+ t cells. this is thought to be the case too for humans. nevertheless, it is possible that successful vaccination elicits antigen-specific antibodies that can serve as co ...	2006	16781667
[evaluation of the enzyme-linked immunosorbent assay for the serodiagnosis of tularemia].	the usefulness of the elisa using as antigen prepared in our laboratory supernatant obtained after centrifugation of sonicated f. tularensis cell suspension was compared with the tube agglutination test with commercial available antigen. paired serum specimens obtained from 6 patients with ulceroglandular syndrome of tularemia were tested in both tests. the cut-off limit of serum antibodies was set at mean antibody titre determined in the sera of 115 blood donors exceeded by three standard devia ...	2005	16773836
tularemia: current epidemiology and disease management.		2006	16762740
characterization of the lipopolysaccharide and beta-glucan of the fish pathogen francisella victoria.	lipopolysaccharide (lps) and beta-glucan from francisella victoria, a fish pathogen and close relative of highly virulent mammal pathogen francisella tularensis, have been analyzed using chemical and spectroscopy methods. the polysaccharide part of the lps was found to contain a nonrepetitive sequence of 20 monosaccharides as well as alanine, 3-aminobutyric acid, and a novel branched amino acid, thus confirming f. victoria as a unique species. the structure identified composes the largest oligos ...	2006	16759227
in vivo proteomic analysis of the intracellular bacterial pathogen, francisella tularensis, isolated from mouse spleen.	understanding the pathogenesis of infectious diseases requires comprehensive knowledge of the proteins expressed by the pathogen during in vivo growth in the host. proteomics provides the tools for such analyses but the protocols required to purify sufficient quantities of the pathogen from the host organism are currently lacking. here, we present a rapid immunomagnetic protocol for the separation of francisella tularensis, a highly virulent bacterium and potential biowarfare agent, from the spl ...	2006	16730660
louse-borne bacterial pathogens in lice (phthiraptera) of rodents and cattle from egypt.	we collected 1,023 lice, representing 5 species, from rats and domestic cattle throughout 13 governorates in egypt and tested these lice for anaplasma marginale, bartonella spp., brucella spp., borrelia recurrentis, coxiella burnetii, francisella tularensis, and rickettsia spp. by pcr amplification and sequencing. five different louse-borne bacterial agents were detected in lice from rodents or cattle, including "bartonella rattimassiliensis", "b. phoceensis", and bartonella sp. near bartonella ...	2006	16729688
toll-like receptor 2 is required for control of pulmonary infection with francisella tularensis.	toll-like receptor 2 (tlr2) deficiency enhances murine susceptibility to infection by francisella tularensis as indicated by accelerated mortality, higher bacterial burden, and greater histopathology. analysis of pulmonary cytokine levels revealed that tlr2 deficiency results in significantly lower levels of tumor necrosis factor alpha and interleukin-6 but increased amounts of gamma interferon and monocyte chemoattractant protein 1. this pattern of cytokine production may contribute to the exag ...	2006	16714598
basis for the failure of francisella tularensis lipopolysaccharide to prime human polymorphonuclear leukocytes.	francisella tularensis is the intracellular gram-negative coccobacillus that causes tularemia, and its virulence and infectiousness make it a potential agent of bioterrorism. previous studies using mononuclear leukocytes have shown that the lipopolysaccharide (lps) of f. tularensis is neither a typical proinflammatory endotoxin nor an endotoxin antagonist. this inertness suggests that f. tularensis lps does not bind host lps-sensing molecules such as lps-binding protein (lbp). using priming of t ...	2006	16714555
immunologic consequences of francisella tularensis live vaccine strain infection: role of the innate immune response in infection and immunity.	francisella tularensis (ft), a gram-negative intracellular bacterium, is the etiologic agent of tularemia. although attenuated for humans, i.p. infection of mice with <10 ft live vaccine strain (lvs) organisms causes lethal infection that resembles human tularemia, whereas the ld50 for an intradermal infection is >10(6) organisms. to examine the immunological consequences of ft lvs infection on the innate immune response, the inflammatory responses of mice infected i.p. or intradermally were com ...	2006	16709849
characterization of the siderophore of francisella tularensis and role of fsla in siderophore production.	we determined that lvs and schu s4 strains of the human pathogen francisella tularensis express a siderophore when grown under iron-limiting conditions. we purified this siderophore by conventional column chromatography and high-pressure liquid chromatography and used mass spectrometric analysis to demonstrate that it is structurally similar to the polycarboxylate siderophore rhizoferrin. the siderophore promoted the growth of lvs and schu s4 strains in iron-limiting media. we identified a poten ...	2006	16707671
raccoons and skunks as sentinels for enzootic tularemia.	we analyzed sera from diverse mammals of martha's vineyard, massachusetts, for evidence of francisella tularensis exposure. skunks and raccoons were frequently seroreactive, whereas white-footed mice, cottontail rabbits, deer, rats, and dogs were not. tularemia surveillance may be facilitated by focusing on skunks and raccoons.	2006	16707067
francisella tularensis in rodents, china.	a total of 420 rodents in china were examined for francisella tularensis by polymerase chain reaction. the infection rates were 4.76% in total, and 11.65%, 10.00%, 6.56%, 1.77%, and 0% in jilin, xinjiang, heilongjiang, inner mongolia, and zhejiang, respectively. sequence analysis showed that all the detected agents belonged to f. tularensis subsp. holarctica.	2006	16707060
tularemia outbreak, bulgaria, 1997-2005.	the 1997-2005 tularemia outbreak in bulgaria affected 285 people. ten strains were isolated from humans, a tick, a hare, and water. amplified fragment length polymorphism typing of the present isolates and of the strain isolated in 1962 suggests that a new genetic variant caused the outbreak.	2006	16704820
francisella tularensis: taxonomy, genetics, and immunopathogenesis of a potential agent of biowarfare.	tularemia is a zoonosis of humans caused by infection with the facultative intracellular bacterium francisella tularensis. interest in f. tularensis has increased markedly in the past few years because of its potential use as an agent of bioterrorism. five subspecies of this organism are found in the northern hemisphere, but only f. tularensis subsp. tularensis and subsp. holarctica cause disease in humans. this review summarizes what is known about the pathogenesis of tularemia with a focus on ...	2006	16704343
environmental survey for four pathogenic bacteria and closely related species using phylogenetic and functional genes.	bacterial species with high dna sequence similarity to pathogens could affect the specificity of assays designed to detect biological threat agents in environmental samples. the natural presence of four pathogenic bacteria, bacillus anthracis, clostridium perfringens, francisella tularensis, and yersinia pestis and their closely related species, was determined for a large collection of soil and aerosol samples. polymerase chain reaction (pcr) and gene sequencing were used using group-specific 16 ...	2006	16696701
a novel systemic granulomatous inflammatory disease in farmed atlantic cod, gadus morhua l., associated with a bacterium belonging to the genus francisella.		2006	16677321
dominance of human innate immune responses in primary francisella tularensis live vaccine strain vaccination.		2006	16675351
the atypical pneumonias: clinical diagnosis and importance.	the most common atypical pneumonias are caused by three zoonotic pathogens, chlamydia psittaci (psittacosis), francisella tularensis (tularemia), and coxiella burnetii (q fever), and three nonzoonotic pathogens, chlamydia pneumoniae, mycoplasma pneumoniae, and legionella. these atypical agents, unlike the typical pathogens, often cause extrapulmonary manifestations. atypical caps are systemic infectious diseases with a pulmonary component and may be differentiated clinically from typical caps by ...	2006	16669925
a simple and rapid protein array based method for the simultaneous detection of biowarfare agents.	a protein chip has been developed that allows the simultaneous detection of a multitude of different biowarfare agents. the chip was developed for the arraytube platform providing a cheap and easy to handle technology solution that combines a microtube-integrated protein chip with the classical procedure of a sandwich-enzyme-linked immunosorbent assay and signal amplification by streptavidin-poly-horseradish peroxidase. specific immunoassays for staphylococcus enterotoxin b, ricin, venezuelan eq ...	2006	16622830
toll-like receptor 2 is required for inflammatory responses to francisella tularensis lvs.	francisella tularensis, a gram-negative bacterium, is the etiologic agent of tularemia and has recently been classified as a category a bioterrorism agent. infections with f. tularensis result in an inflammatory response that plays an important role in the pathogenesis of the disease; however, the cellular mechanisms mediating this response have not been completely elucidated. in the present study, we determined the role of toll-like receptors (tlrs) in mediating inflammatory responses to f. tul ...	2006	16622218
treatment of murine pneumonic francisella tularensis infection with gatifloxacin, moxifloxacin or ciprofloxacin.	the efficacies of gatifloxacin and moxifloxacin were assessed in a balb/c mouse model of pneumonic tularemia and compared with the efficacy of ciprofloxacin. the rate of relapse following dexamethasone treatment was also investigated. mice were given 100 mg/kg of the antibiotic by oral administration twice daily for 14 days following an aerosol challenge. all three fluoroquinolones prevented disease during the treatment period, but significant failure rates occurred after the cessation of therap ...	2006	16621457
[tularaemia as a differential diagnosis in tumour colli].	tularaemia is a bacterial zoonosis caused by the bacterium francisella tularensis. different species of rodents and small mammals are the main reservoir; the transmission of disease is caused by direct contact with diseased animals, via insect vectors, or by ingestion of contaminated food and water. the disease is known to cause a complex clinical presentation in which head and neck manifestations are common. it occurs at a low annual rate in the northern and middle regions of norway, but in rec ...	2006	16619065
francisella sp. (family francisellaceae) causing mortality in norwegian cod (gadus morhua) farming.	in 2004, a new disease was detected in cod (gadus morhua) in western norway. affected cod had white granulomas in the visceral organs and skin. a species of francisella was isolated on blood agar plates from moribund cod. the bacterium could be grown at temperatures ranging from 6 to 22 degrees c, but did not grow at 37 degrees c. challenge experiments showed that francisella sp. was the cause for the new disease. the 16s rdna gene sequence from francisella sp. showed 99.17% similarity to f. phi ...	2006	16614828
francisella tularensis lps induces the production of cytokines in human monocytes and signals via toll-like receptor 4 with much lower potency than e. coli lps.	francisella tularensis is a virulent gram-negative intracellular pathogen. to address the signaling routes involved in the response of host cells to lps from f. tularensis live vaccine strain (lvs), experiments were performed in transiently transfected 293 cells. induction of kappab-driven transcriptional activity by 2.5 mug ml(-1) f. tularensis lps isolated by phenol-water and ether-water extraction, was observed in cells transfected with toll-like receptor (tlr) 4 and md-2, although cd14 was r ...	2006	16574669
tularemia induced bilateral optic neuritis.		2006	16562762
direct repeat-mediated deletion of a type iv pilin gene results in major virulence attenuation of francisella tularensis.	francisella tularensis, the causative agent of tularaemia, is a highly infectious and virulent intracellular pathogen. there are two main human pathogenic subspecies, francisella tularensis ssp. tularensis (type a), and francisella tularensis ssp. holarctica (type b). so far, knowledge regarding key virulence determinants is limited but it is clear that intracellular survival and multiplication is one major virulence strategy of francisella. in addition, genome sequencing has revealed the presen ...	2006	16553886
intranasal vaccination with a defined attenuated francisella novicida strain induces gamma interferon-dependent antibody-mediated protection against tularemia.	francisella tularensis is an intracellular gram-negative bacterium that is the causative agent of tularemia and a potential bioweapon. we have characterized the efficacy of a defined f. novicida mutant (deltaiglc) as a live attenuated vaccine against subsequent intranasal challenge with the wild-type organism. animals primed with the f. novicida deltaiglc (kkf24) mutant induced robust splenic gamma interferon (ifn-gamma) and interleukin-12 (il-12) recall responses with negligible il-4 production ...	2006	16552035
anti-francisella tularensis dna aptamers detect tularemia antigen from different subspecies by aptamer-linked immobilized sorbent assay.	aptamers are powerful candidates for molecular detection of targets due to their unique recognition properties. these affinity probes can be used to recognize and bind to their targets in the various types of assays that are currently used to detect and capture molecules of interest. they are short single-stranded (ss) oligonucleotides composed of dna or rna sequences that are selected in vitro based on their affinity and specificity for the target. using combinatorial oligonucleotide libraries, ...	2006	16550191
[persistence factors of francisella tularensis].	the study of the persistence potential of 64 f. tularensis strains isolated from different sources was carried out. the wide spread of the antilysozyme, antilactoferrin and anticomplementory activities of f. tularensis were detected. f. tularensis, isolated from ticks and water, were characterized by the highest level of the expression of antilysozyme activity, while anticomplementory and antilactoferrin activities of the infective agents were characteristic of those microorganisms which were is ...	2006	16532645
an outbreak of airborne tularaemia in france, august 2004.	fifteen tularaemia cases were identified after a holiday spent at a converted mill in the vendee region in france, between 9 and 12 august 2004. the mill was visited, and descriptive, retrospective cohort and environmental investigations were conducted. the 39 people who had stayed at the mill between 24 july and 11 august were asked about symptoms, exposure to food and animals, and leisure activities. a case was defined as a person with evidence of fever and a positive serology (seroconversion ...	2006	16525197
in vivo himar1-based transposon mutagenesis of francisella tularensis.	francisella tularensis is the intracellular pathogen that causes human tularemia. it is recognized as a potential agent of bioterrorism due to its low infectious dose and multiple routes of entry. we report the development of a himar1-based random mutagenesis system for f. tularensis (himarft). in vivo mutagenesis of f. tularensis live vaccine strain (lvs) with himarft occurs at high efficiency. approximately 12 to 15% of cells transformed with the delivery plasmid result in transposon insertion ...	2006	16517634
myeloid differentiation factor-88 (myd88) is essential for control of primary in vivo francisella tularensis lvs infection, but not for control of intra-macrophage bacterial replication.	the means by which francisella tularensis, the causative agent of tularemia, are recognized by mammalian immune systems are poorly understood. here we wished to explore the contribution of the myd88/toll-like receptor signaling pathway in initiating murine responses to f. tularensis live vaccine strain (lvs). myd88 knockout (ko) mice, but not tlr2-, tlr4- or tlr9-deficient mice, rapidly succumbed following in vivo bacterial infection via the intradermal route even with a very low dose of lvs (5 ...	2006	16513388
selected microbial agents in snowshoe hares and other vertebrates of alberta.	serologic surveillance of populations of snowshoe hares and other vertebrate species of north-central alberta from 1961 to 1969, revealed activity of one bacterial and eight viral agents. the most prevalent agents infecting the snowshoe hare were california encephalitis and silverwater viruses, while in other vertebrates california encephalitis and western equine encephalomyelitis viruses were the most common. the role of the snowshoe hare in the natural history of the agents is considered as is ...	1970	16512159
crystallization of a newly discovered histidine acid phosphatase from francisella tularensis.	francisella tularensis is a highly infectious bacterial pathogen that is considered by the centers for disease control and prevention to be a potential bioterrorism weapon. here, the crystallization of a 37.2 kda phosphatase encoded by the genome of f. tularensis subsp. holarctica live vaccine strain is reported. this enzyme shares 41% amino-acid sequence identity with legionella pneumophila major acid phosphatase and contains the rhgxrxp motif that is characteristic of the histidine acid phosph ...	2006	16511256
antibiotic selection and resistance issues with fluoroquinolones and doxycycline against bioterrorism agents.	bacillus anthracis (anthrax), yersinia pestis (plague), francisella tularensis (tularemia), coxiella burnetti (q fever), and brucella sp (brucellosis) are all potential bioterrorism agents. their known virulence, potential lethality, and ability to develop resistance to known antibiotic treatments make these pathogens particularly dangerous. we reviewed the scientific literature by searching medline databases and published abstracts from the interscience conference on antimicrobial agents and ch ...	2006	16506347
the identification and evaluation of atp binding cassette systems in the intracellular bacterium francisella tularensis.	francisella tularensis is a facultative intracellular bacterium responsible for the disease tularemia. analysis of the fully sequenced genome of the virulent f. tularensis strain schu s4 has led to the identification of twenty atp binding cassette (abc) systems, of which five appear to be non-functional. the fifteen complete systems comprise three importers, five exporters, four systems involved in non-transport processes, and three systems of unknown or ill-defined function. the number and clas ...	2006	16503121
tularemia in a mule deer.	a case of tularemia was confirmed in a 51-year-old man who acquired the disease from a mule deer, odocoileus hemionus. francisella tularensis was isolated from bone marrow of the deer carcass.	1976	16498895
development of a real-time pcr assay for detection and quantification of francisella tularensis.	the facultative intracellular bacterium, francisella tularensis, is an etiological agent of tularemia and is also considered to be a potential biological threat agent due to its extreme infectivity. we established a real-time pcr assay using the lightcycler (lc) system to detect a francisella-specific sequence of the outer membrane protein (fopa) gene. twenty-five f. tularensis strains including 16 japanese isolates were subjected to this lc-pcr assay, and were tested positive, whereas francisel ...	2006	16495634
francisella tularensis in the united states.	the causative agent of tularemia, francisella tularensis, is a formidable biologic agent that occurs naturally throughout north america. we examined genetic and spatial diversity patterns among 161 us f. tularensis isolates by using a 24-marker multiple-locus variable-number tandem repeat analysis (mlva) system. mlva identified 126 unique genotypes. phylogenetic analyses showed patterns similar to recently reported global-scale analyses. we observed clustering by subspecies, low genetic diversit ...	2005	16485467
fiber-optic microsphere-based arrays for multiplexed biological warfare agent detection.	we report a multiplexed high-density dna array capable of rapid, sensitive, and reliable identification of potential biological warfare agents. an optical fiber bundle containing 6000 individual 3.1-mum-diameter fibers was chemically etched to yield microwells and used as the substrate for the array. eighteen different 50-mer single-stranded dna probes were covalently attached to 3.1-mum microspheres. probe sequences were designed for bacillus anthracis, yersinia pestis, francisella tularensis, ...	2006	16478092
transcriptional profiling of host responses in mouse lungs following aerosol infection with type a francisella tularensis.	tularaemia caused by inhalation of type a francisella tularensis bacteria is one of the most aggressive infectious diseases known, but the reasons for the very rapid spread of the organism from the lungs to internal organs and the ensuing mortality are unknown. the present study used the mouse model to examine in detail the host immune response in the lung. after an aerosol challenge with 20 c.f.u. of the type a strain fsc033, all mice developed clinical signs of severe disease, showed weight lo ...	2006	16476789
expression cloning and periplasmic orientation of the francisella novicida lipid a 4'-phosphatase lpxf.	francisella tularensis and related intracellular pathogens synthesize lipid a molecules that differ from their escherichia coli counterparts. although a functional orthologue of lpxk, the gene encoding the lipid a 4'-kinase, is present in francisella, no 4'-phosphate moiety is attached to francisella lipid a. we now demonstrate that a membrane-bound phosphatase present in francisella novicida u112 selectively removes the 4'-phosphate residue from tetra- and pentaacylated lipid a molecules. a clo ...	2006	16467300
serologic survey of select infectious diseases in coyotes and raccoons in nebraska.	to obtain data about select zoonotic and other infectious diseases in free-ranging predators in five ecoregions in nebraska, sera were collected from 67 coyotes (canis latrans) and 63 raccoons (procyon lotor) from november 2002 through january 2003. for coyotes, antibodies were detected against canine distemper virus (cdv, 61%), francisella tularensis (32%), rickettsia rickettsi (13%), and flaviviruses (48%). none of the coyote sera had antibodies to borrelia burgdorferi, brucella canis, or six ...	2005	16456169
virulence comparison in mice of distinct isolates of type a francisella tularensis.	francisella tularensis subspecies tularensis (type a f. tularensis) is considered to be one of the most virulent of all bacterial pathogens. mice are extremely susceptible to infection with this subspecies (ld100 via various inoculation routes is <10 cfu). however, it has not been established whether overt virulence differences exist amongst type a strains of f. tularensis. to this end, the present study compared the virulence of two distinct type a strains, fsc033 and schu s4, for naïve mice an ...	2006	16448801
[rickettsia helvetica: an emerging tick-borne pathogen in hungary and europe].	rickettsia helvetica belonging to spotted fever group rickettsiae was recently detected by polymerase chain reaction followed by sequencing in european sheep ticks (ixodes ricinus) from hungary. current knowledge on these rickettsiae and the clinical and diagnostic aspects of r. helvetica infection is summarized. in acute cases, r. helvetica is generally responsible for flu-like symptoms. nevertheless, recent data indicate that in chronic cases, these rickettsiae can be responsible for perimyoca ...	2005	16440500
bacterial cell microarrays for the detection and characterization of antibodies against surface antigens.	bacterial cell surface antigens interact with the host immune system resulting in the production of antibodies. detection of antibodies against surface antigens has applications in diagnosis of many bacterial infections, assessment of immune status and epidemiological studies. we developed a microarray platform, for antibody detection, by printing gram-negative and gram-positive whole bacterial cells on nitrocellulose coated glass substrates. antibody binding was detected using fluorophore label ...	2006	16423364
cryopyrin activates the inflammasome in response to toxins and atp.	a crucial part of the innate immune response is the assembly of the inflammasome, a cytosolic complex of proteins that activates caspase-1 to process the proinflammatory cytokines interleukin (il)-1beta and il-18. the adaptor protein asc is essential for inflammasome function, binding directly to caspase-1 (refs 3, 4), but the triggers of this interaction are less clear. asc also interacts with the adaptor cryopyrin (also known as nalp3 or cias1). activating mutations in cryopyrin are associated ...	2006	16407890
h2bc: a new technique for nmr analysis of complex carbohydrates.	it is demonstrated that the h2bc nmr pulse sequence (j. am. chem. soc.2005, 127, 6154, magn. reson. chem.2005, 43, 971-974) offers unambiguous assignments and significant simplification of nmr spectra of large and complex carbohydrates compared to other techniques for the establishment of correlations over more than one bond. h2bc almost exclusively correlates protons and proton-bearing carbon spins separated by two covalent bonds and is independent of occasionally vanishing (2)j(ch) coupling co ...	2006	16406276
[incidence of zoonoses in petting zoos and evaluation of hygiene measures to prevent the transmission to humans].	in summer 2003, a study was performed in thirty swiss petting zoos with the objective to determine the prevalence of zoonotic agents, and to describe hygiene measures implemented to reduce the risk of human infection. fecal samples from different animal species were collected from the floor of pens to determine the prevalence of salmonella spp., campylobacter spp., verocytotoxin producing e. coli/ vtec and francisella tularensis. a questionnaire on hygiene measures, number of animals per species ...	2005	16398191
detection of biological threat agents by real-time pcr: comparison of assay performance on the r.a.p.i.d., the lightcycler, and the smart cycler platforms.	rapid detection of biological threat agents is critical for timely therapeutic administration. fluorogenic pcr provides a rapid, sensitive, and specific tool for molecular identification of these agents. we compared the performance of assays for 7 biological threat agents on the idaho technology, inc. r.a.p.i.d., the roche lightcycler, and the cepheid smart cycler.	2006	16391330
natural killer and cd8 t cells dominate the response by human peripheral blood mononuclear cells to inactivated francisella tularensis live vaccine strain.	francisella tularensis is a category a biothreat agent, and as a result, it has recently generated much research interest. f. tularensis live vaccine strain (lvs) is an attenuated form of the virulent f. tularensis organism and has previously been used as a vaccine. however, because of safety concerns, it is no longer approved for this purpose. thus, the use of inactivated organisms is preferable for vaccine purposes. although many studies have been performed that examine human peripheral blood ...	2005	16386645
internalization and phagosome escape required for francisella to induce human monocyte il-1beta processing and release.	macrophage responses to francisella infection have been characterized previously by subdued proinflammatory responses; however, these studies have generally focused on macrophage cell lines or monocyte-derived macrophages. therefore, we studied the ability of fresh human blood monocytes to engulf and respond to francisella by using the live vaccine strain variant and francisella novicida. because francisella organisms have been reported to escape from the phagolysosome into the cytosol, we hypot ...	2006	16373510
seroprevalence of brucellosis, tularemia, and yersiniosis in wild boars (sus scrofa) from north-eastern germany.	brucellosis and tularemia are classical zoonotic diseases transmitted from an animal reservoir to humans. both, wildlife and domestic animals, contribute to the spreading of these zoonoses. the surveillance of the animal health status is strictly regulated for domestic animals, whereas systematic disease monitoring in wildlife does not exist. the aim of the present study was to provide data on the prevalence of anti-brucella, anti-francisella and anti-yersinia antibodies in wild boars from north ...	2005	16364020
francisella tularensis travels a novel, twisted road within macrophages.	francisella tularensis is a highly infectious intracellular bacterium that causes fulminating disease and is a potential bioweapon. although entry of the bacteria into macrophages is mediated by novel asymmetric, spacious pseudopod loops, the nascent phagosome becomes tight fitting within seconds of formation. biogenesis of the francisella-containing phagosome (fcp) is arrested for 2-4h at a unique stage within the endosomal-lysosomal degradation pathway, followed by gradual bacterial escape int ...	2006	16356719
clinical use of a diagnostic pcr for francisella tularensis in patients with suspected ulceroglandular tularaemia.	a retrospective analysis to evaluate the clinical use of a diagnostic pcr for francisella tularensis in patients with suspected ulceroglandular tularaemia was performed. 154 samples, 129 from patients with definitive tularaemia and 25 from patients where tularaemia could be ruled out, were analysed. the diagnostic pcr had a specificity of 96%, a sensitivity of 78.3%, and a positive predictive value of 99%. especially samples from encrusted lesions, even up to 4 weeks old, in patients with tulara ...	2005	16308216
a mutant of francisella tularensis strain schu s4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine.	francisella tularensis subsp. tularensis (type a) strain schu s4 is a prototypic strain of the pathogen that is highly virulent for humans and other mammals. its intradermal (i.d.) 50% lethal dose (ld50) for mice is <10 cfu. we discovered a spontaneous mutant, designated fsc043, of schu s4 with an i.d. ld50 of >10(8) cfu. fsc043 effectively vaccinated mice against challenge with a highly virulent type a strain, and the protective efficacy was at least as good as that of f. tularensis lvs, an emp ...	2005	16299332
a 12-case outbreak of pharyngeal plague following the consumption of camel meat, in north-eastern jordan.	between late january and early february 1997, an outbreak of plague, associated with cervical lymphadenopathy and fever, occurred in the jordanian village of azraq ad-druze, which lies about 50 km west of the border with saudi arabia. the 12 cases who presented at hospital were initially assumed to have tularaemia, and all were successfully treated with gentamicin. when, however, their sera were tested for evidence of yersinia pestis or francisella tularensis infection (using haemagglutination, ...	2005	16297292
[bioterrorism].	biological terrorism is intentionally to use infectious substances for developing diseases or death in animals or humans, leading to disaster and panic in our community. bioterrorism-associated diseases are mostly rare or eradicated infectious diseases, and recently, we do not have experience to make a clinical and laboratory diagnosis. in particular, these infectious diseases have incubation periods from infection to development of the disease. the staff working at public health institutions, i ...	2005	16296383
[rodents as the vectors of infective agents in the natural foci of infections in the moscow megapolis].	this work deals with the results of 40-year observations on the circulation of infective agents in the natural foci of infections (tularemia, leptospirosis, hemorrhagic fever with renal syndrome) among rodents and other small mammals in the territory of the moscow. the monitoring of their frequency and the infection rates remains the main effective measure for the prophylaxis of dangerous infections among the population of the megapolis.	2005	16279545
francisella tularensis induces aberrant activation of pulmonary dendritic cells.	francisella tularensis is an obligate intracellular bacterium that induces severe, acute, often fatal disease when acquired by the respiratory route. despite the seriousness of this pathogen, very little is understood about its interaction with key target cells in the airways and lungs (alveolar macrophages and airway dendritic cells (dc)) after inhalation. in this study we demonstrate replication of f. tularensis in primary dc. early after infection, f. tularensis induced increased expression o ...	2005	16272336
discrimination between francisella tularensis and francisella-like endosymbionts when screening ticks by pcr.	the presence of francisella-like endosymbionts in tick species known to transmit tularemia poses a potential diagnostic problem for laboratories that screen tick samples by pcr for francisella tularensis. tick samples initially considered positive for f. tularensis based on standard 16s rrna gene pcr were found to be positive only for francisella-like endosymbionts using a multitarget f. tularensis taqman assay (isftu2, tul4, and iglc) and 16s rrna gene sequencing. specificity of pcr-based diagn ...	2005	16269811
low dose aerosol infection of mice with virulent type a francisella tularensis induces severe thymus atrophy and cd4+cd8+ thymocyte depletion.	francisella tularensis is a gram-negative facultative intracellular bacterium and the causative agent of tularemia. two subspecies (type a and b strains) of the pathogen exist, the former being much more virulent than the latter for humans and other higher mammals. in this study, we examined the effect of virulent strains of f. tularensis infection on the thymus and thymocytes and the potential mechanisms involved. low-dose aerosol exposure of c57bl/6 mice with type a, but not type b, f. tularen ...	2005	16257504
grey variants of the live vaccine strain of francisella tularensis lack lipopolysaccharide o-antigen, show reduced ability to survive in macrophages and do not induce protective immunity in mice.	francisella tularensis live vaccine strain (lvs) produces two colony types when grown on solid media, often referred to as blue variants (bv) and grey variants (gv). whereas blue variant bacteria possessed a lipopolysaccharide o-side chain, grey variant bacteria lacked o-side chains. grey variant bacteria appeared in stationary phase bacterial cultures and could be identified using a novel facs-based assay. compared to blue variant bacteria, grey variants showed a reduced ability to infect and s ...	2006	16257097
[the interaction of dynamic speckles with suspensions of gram-negative cells].	the role of temporal coherence at photodynamic action of light on living cells was investigated. a mathematical model describing the interaction of low-coherent speckles with bacterial cells was suggested and its parameters were determined based on experimental data. the interrelation between the life time of dynamic optical speckles and the degree of photodestruction of illuminated cells was established by computer simulations. the conditions were determined under which the photoinactivation of ...	2005	16248164
intracellular survival mechanisms of francisella tularensis, a stealth pathogen.	research on the highly virulent and contagious, facultative intracellular bacterium francisella tularensis has come into the limelight recently, but still little is known regarding its virulence mechanisms. this review summarizes recent studies on its intramacrophage survival mechanisms, some of which appear to be novel.	2006	16239121
a multiplex polymerase chain reaction microarray assay to detect bioterror pathogens in blood.	heightened concern about the dangers of bioterrorism requires that measures be developed to ensure the safety of the blood supply. multiplex detection of such agents using a blood-screening dna microarray is a sensitive and specific method to screen simultaneously for a number of suspected agents. we have developed and optimized a multiplex polymerase chain reaction microarray assay to screen blood for three potential bioterror bacterial pathogens and a human ribosomal rna gene internal control. ...	2005	16237218
innate immunity against francisella tularensis is dependent on the asc/caspase-1 axis.	francisella tularensis is a highly infectious gram-negative coccobacillus that causes the zoonosis tularemia. this bacterial pathogen causes a plague-like disease in humans after exposure to as few as 10 cells. many of the mechanisms by which the innate immune system fights francisella are unknown. here we show that wild-type francisella, which reach the cytosol, but not francisella mutants that remain localized to the vacuole, induced a host defense response in macrophages, which is dependent o ...	2005	16230474
in vivo efficacy of fluoroquinolones against systemic tularaemia infection in mice.	the in vivo efficacy of ciprofloxacin, gatifloxacin and moxifloxacin were assessed in an experimental francisella tularensis schu s4 infection in the balb/c mouse model.	2005	16223941
diagnostic procedures in tularaemia with special focus on molecular and immunological techniques.	tularaemia is a severe bacterial zoonosis caused by the highly infectious agent francisella tularensis. it is endemic in countries of the northern hemisphere ranging from north america to europe, asia and japan. very recently, francisella-like strains causing disease in humans were described from tropical northern australia. in the last decade, efforts have been made to develop sensitive and specific immunological and molecular techniques for the laboratory diagnosis of tularaemia and also for t ...	2005	16219088
francisella tularensis proteome: low levels of asb-14 facilitate the visualization of membrane proteins in total protein extracts.	proteomic analysis of bacterial pathogens isolated from in vivo sources, such as infected tissues, provides many challenges not the least of which is the limited quantity of sample available for analysis. it is, therefore, highly desirable to develop a one-step cellular lysis and protein solubilization method that minimizes protein losses and allows the maximum possible coverage of the proteome. here, we have used standard sample buffer constituents including urea, thiourea and dtt, but varied t ...	2005	16212441
[tularemia].		2005	16209241
tularemia in denmark: identification of a francisella tularensis subsp. holarctica strain by real-time pcr and high-resolution typing by multiple-locus variable-number tandem repeat analysis.	we report ulceroglandular tularemia affecting an 8-year-old boy and the first recovery of francisella tularensis in denmark. a novel real-time pcr assay was used to identify the strain as f. tularensis subsp. holarctica (type b). multiple-locus variable-number tandem repeat analysis demonstrated a close genetic relationship to strains from norway.	2005	16208017
use of shell-vial cell culture assay for isolation of bacteria from clinical specimens: 13 years of experience.	the shell-vial culture assay is performed routinely in our laboratory. recently we revisited our experience of using the shell-vial culture assay for the isolation of microorganisms from various clinical samples. over a 13-year period, we have isolated 580 bacterial strains (5%) from 11,083 clinical samples tested. over the same period, 285 isolates of rickettsiae, bartonellae, or coxiella burnetii were cultured from a total of 7,102 samples tested. these isolates include 55 rickettsia sp. isola ...	2005	16207953
outbreak of tularaemia in golcuk, turkey in 2005: report of 5 cases and an overview of the literature from turkey.	tularaemia was diagnosed by taqman rt-pcr and microagglutination tests in 5 patients, all from a new settlement constructed after the earthquake of 1999. during the follow-up, 129 more cases were found in this settlement (data from the local health care authority). in this study, clinical features of 5 cases are presented briefly, and the turkish literature on past outbreaks of tularaemia is reviewed.	2005	16191887
detection of diverse new francisella-like bacteria in environmental samples.	following detection of putative francisella species in aerosol samples from houston, texas, we surveyed soil and water samples from the area for the agent of tularemia, francisella tularensis, and related species. the initial survey used 16s rrna gene primers to detect francisella species and related organisms by pcr amplification of dna extracts from environmental samples. this analysis indicated that sequences related to francisella were present in one water and seven soil samples. this is the ...	2005	16151142
[phase variations of francisella tularensis lipopolysaccharide in human infection and immunization].	the comparative study of the specificity of antibodies in human sera after tularemia infection and immunization with live tularemia infection was carried out with the use of passive hemagglutination and immunoblotting techniques. the sera of tularemia patients contained two different types of immunoglobulins: strictly specific to the antigenic epitopes of f. tularensis iipopolysaccharide (lps) and strictly specific to f. tularensis subsp. novicida lps. such phenomenon may be due to phase variati ...	2005	16146218
antimicrobial susceptibilities of austrian francisella tularensis holarctica biovar ii strains.	the antibiotic susceptibilities of 50 francisella tularensis subsp. holarctica biovar ii strains isolated from hares and human patients from the eastern part of austria were examined. minimum inhibitory concentrations (mics) of 24 antimicrobial agents were determined using eteststrade mark on cysteine heart agar plates supplemented with 10% sheep blood. all isolates were sensitive to tetracyclines, aminoglycosides, quinolones, chloramphenicol and rifampicin. resistance was observed in all isolat ...	2005	16143497
francisella tularensis enters macrophages via a novel process involving pseudopod loops.	intracellular bacterial pathogens employ a variety of strategies to invade their eukaryotic host cells. from an ultrastructural standpoint, the processes that bacteria employ to invade their host cells include conventional phagocytosis, coiling phagocytosis, and ruffling/triggered macropinocytosis. in this paper, we describe a novel process by which francisella tularensis, the agent of tularemia, enters host macrophages. f. tularensis is a remarkably infectious facultative intracellular bacteria ...	2005	16113308
[diagnostic tests: tularemia].		2005	16111241
dna assays for detection, identification, and individualization of select agent microorganisms.	the purpose of this article is to review the status of dna assays used for the detection, identification, and individualization of bacillus anthracis, yersinia pestis, francisella tularensis, burkholderia mallei, and brucella abortus. these select agent microorganisms are historically significant as they have either been used or experimented with as a bioweapon or as a terrorist agent and are the subject of intense research in the areas of biodefense and bioforensics. if the presence of a biolog ...	2005	16100754
massive attack.		2005	16094740
enteric fever-like illness caused by infection with citrobacter amalonaticus.	'enteric fever' is a potentially fatal, severe systemic disease, which is encountered worldwide. traditionally, enteric fever refers to a bacteremic illness caused by members of certain salmonella serotypes, notably: salmonella typhi, a gram-negative bacterium, and to a lesser extent, salmonella paratyphi a, b and c. in addition, other non-salmonella organisms may produce a syndrome clinically indistinguishable from "enteric fever". brucella sp., campylobacter sp., edwardsiella tarda, enterobact ...	2005	16083226
a novel screening elisa and a confirmatory western blot useful for diagnosis and epidemiological studies of tularemia.	a novel enzyme-linked immunosorbent assay (elisa) and a confirmatory western blot (wb) to detect human antibodies against francisella tularensis were evaluated. the elisa was based on partially purified lipopolysaccharide (lps), the wb on whole antigen of f. tularensis. positive wb showed a typical lps ladder. sensitivity and specificity of the elisa, as assessed in 104 positive sera and 1149 'normal' sera from healthy young adults, were 99.0% and 97.1% respectively. sensitivity of the wb was cl ...	2005	16050523
prevalence of infection with francisella tularensis, borrelia burgdorferi sensu lato and anaplasma phagocytophilum in rodents from an endemic focus of tularemia in bulgaria.	the prevalence of francisella tularensis, borrelia burgdorferi and anaplasma phagocytophilum in rodents is a determinant for their role in maintaining pathogens in the environment. a total of 169 rodents, trapped in an endemic focus of tularemia, were examined by pcr to asses the frequency of infection with the etiological agents of tularemia, lyme borreliosis and human granulocytic anaplasmosis. the overall prevalence of f. tularensis was 22 %. in 6 % of the black rats, f. tularensis was identi ...	2005	16028881
[influence of cycloferon on the biological properties of bacterial intracellular pathogens].	the influence of cycloferon on some biological properties of pathogenic (shigella spp., salmonella spp., francisella tularensis, brucella spp.) and opportunistic (escherichia coli, staphylococcus spp.) microorganisms has been experimentally determined in vitro. as revealed in these experiments, the preparation used at concentrations under study considerably suppresses the antilysozyme and anticomplementary activity of gram-negative intracellular parasites (shigellae, salmonellae, f. tularensis, ...	2005	16028504
cd4-cd8- t cells control intracellular bacterial infections both in vitro and in vivo.	memory t cells, including the well-known cd4(+) and cd8(+) t cells, are central components of the acquired immune system and are the basis for successful vaccination. after infection, cd4(+) and cd8(+) t cells expand into effector cells, and then differentiate into long-lived memory cells. we show that a rare population of cd4(-)cd8(-)cd3(+)alphabeta(+)gammadelta(-)nk1.1(-) t cells has similar functions. these cells potently and specifically inhibit the growth of the intracellular bacteria mycob ...	2005	16027239
the phagosomal transporter a couples threonine acquisition to differentiation and replication of legionella pneumophila in macrophages.	differentiation in response to environmental cues is integral to the success of many intracellular pathogens. by characterizing a legionella pneumophila mutant defective for differentiation in broth and replication in macrophages, we identified a subfamily of major facilitator superfamily transporters, here named pht (phagosomal transporter), that also is conserved in two other vacuolar pathogens, coxiella burnetii and francisella tularensis. biolog phenotype microarray analysis indicated that p ...	2005	15998735
characterization of recombinant francisella tularensis acid phosphatase a.	francisella tularensis is the etiologic agent of the potentially fatal human disease tularemia and is capable of survival and multiplication within professional phagocytes of the host. while the mechanisms that allow intracellular survival of the bacterium are only now beginning to be elucidated at the molecular level, previous work demonstrated that f. tularensis produces copious levels of an acid phosphatase which in crude and purified form affected the dose-dependent abrogation of the respira ...	2006	15964202
a new francisella (beggiatiales: francisellaceae) inquiline within dermacentor variabilis say (acari: ixodidae).	while estimating the prevalence of the dermacentor variabilis (say) symbiont (dvs) in dog ticks on martha's vineyard, ma, we identified dna that may represent a heretofore unrecognized francisella sp. polymerase chain reaction targeting a portion of the 16s rdna specific for dvs yielded an amplicon that was only 96.6% similar to that of dvs accessioned in genbank. phylogenetic analysis of the 16s and 23s rdna genes suggests the presence of a distinct bacterium closely related to the other endosy ...	2005	15962806
chips and snps, bugs and thugs: a molecular sleuthing perspective.	recent events both here and abroad have focused attention on the need for ensuring a safe and secure food supply. although much has been written about the potential of particular select agents in bioterrorism, we must consider seriously the more mundane pathogens, especially those that have been implicated previously in foodborne outbreaks of human disease, as possible agents of bioterrorism. given their evolutionary history, the enteric pathogens are more diverse than agents such as bacillus an ...	2005	15954721