Publications

TitleAbstractYear
Filter
PMID(sorted ascending)
Filter
characteristics of the turkish isolates of francisella tularensis.in this study, cultures of patients with tularemia were evaluated, and antimicrobial susceptibilities of two francisella tularensis strains were tested by disk diffusion and e-test methods. a high-resolution multiple-locus variable-number tandem repeat analysis (mlva) comprising six variable-number tandem repeat loci was applied to elucidate the genetic relatedness among turkish and bulgarian isolates which were isolated in a recent outbreak. the patients were diagnosed in two outbreaks in two c ...200818503176
native outer membrane proteins protect mice against pulmonary challenge with virulent type a francisella tularensis.francisella tularensis is a gram-negative intracellular bacterium and the causative agent of the zoonotic disease tularemia. f. tularensis is a category a select agent and thus a potential agent of bioterrorism. whereas an f. tularensis live, attenuated vaccine strain (lvs) is the basis of an investigational vaccine, this vaccine is not licensed for human use because of efficacy and safety concerns. in the present study, we immunized mice with isolated native outer membrane proteins (omps), etha ...200818505805
microfluidic-based cell sorting of francisella tularensis infected macrophages using optical forces.we have extended the principle of optical tweezers as a noninvasive technique to actively sort hydrodynamically focused cells based on their fluorescence signal in a microfluidic device. this micro fluorescence-activated cell sorter (microfacs) uses an infrared laser to laterally deflect cells into a collection channel. green-labeled macrophages were sorted from a 40/60 ratio mixture at a throughput of 22 cells/s over 30 min achieving a 93% sorting purity and a 60% recovery yield. to rule out po ...200818510341
francisella gains a survival advantage within mononuclear phagocytes by suppressing the host ifngamma response.tularemia is a zoonotic disease caused by the gram-negative intracellular pathogen francisella tularensis. these bacteria evade phagolysosomal fusion, escape from the phagosome and replicate in the host cell cytoplasm. ifngamma has been shown to suppress the intra-macrophage growth of francisella through both nitric oxide-dependent and -independent pathways. since francisella is known to subvert host immune responses, we hypothesized that this pathogen could interfere with ifngamma signaling. he ...200818514317
francisella targets cholesterol-rich host cell membrane domains for entry into macrophages.francisella tularensis is a pathogen optimally adapted to efficiently invade its respective host cell and to proliferate intracellularly. we investigated the role of host cell membrane microdomains in the entry of f. tularensis subspecies holarctica vaccine strain (f. tularensis live vaccine strain) into murine macrophages. f. tularensis live vaccine strain recruits cholesterol-rich lipid domains ("lipid rafts") with caveolin-1 for successful entry into macrophages. interference with lipid rafts ...200818523292
interaction of b cells with intracellular pathogen francisella tularensis.immunity to francisella tularensis is largely mediated by t lymphocytes but an important role of b lymphocytes in early stage of infection was previously uncovered. we wanted to find out if f. tularensis is able to infect b cells and/or influence them by direct contact. to investigate this possibility we infected b cell lines from mouse (a20) or humans (ramos ra-1), or primary mouse spleen cells, with f. tularensis lvs and f. tularensis fsc200 in vitro. in all cases, we detected bacteria on the ...200818524531
inhalation of francisella novicida delta mgla causes replicative infection that elicits innate and adaptive responses but is not protective against invasive pneumonic tularemia.francisella tularensis causes the zoonosis tularemia in humans, and inhaled f. tularensis ssp. novicida induces lethal murine tularemia. transcription of virulence factors in f. novicida is regulated by macrophage growth locus a (mgla), a global regulator required for bacterial replication in macrophages in vitro. we examined the infectivity and immunogenicity of attenuated f. novicida delta mgla in the lung in vivo. aerosolized delta mgla caused replicative pulmonary infection that peaked at 7 ...200818539500
fsle is necessary for siderophore-mediated iron acquisition in francisella tularensis schu s4.strains of francisella tularensis secrete a siderophore in response to iron limitation. siderophore production is dependent on fsla, the first gene in an operon that appears to encode biosynthetic and export functions for the siderophore. transcription of the operon is induced under conditions of iron limitation. the fsl genes lie adjacent to the fur homolog on the chromosome, and there is a canonical fur box sequence in the promoter region of fsla. we generated a deltafur mutant of the schu s4 ...200818539739
borrelia burgdorferi sensu lato, anaplasma phagocytophilum, francisella tularensis and their co-infections in host-seeking ixodes ricinus ticks collected in serbia.to evaluate the prevalence rate of tick-borne bacterial pathogens, unfed adult ixodes ricinus ticks were collected from vegetation in 2001, 2003, and 2004 at 18 localities throughout serbia. a total of 287 ticks were examined by pcr technique for the presence of borrelia burgdorferi sensu lato, anaplasma phagocytophilum, and francisella tularensis. the highest prevalence rate was that for b. burgdorferi sensu lato (42.5%), followed by a. phagocytophilum (13.9%) and f. tularensis (3.8%). the pres ...200818551370
pericardial effusion as the only manifestation of infection with francisella tularensis: a case report.francisella tularensis, a facultative intracellular gram-negative bacterium, has rarely been reported as an agent of pericarditis, generally described as a complication of tularemia sepsis. f. tularensis is a fastidious organism that grows poorly on standard culture media and diagnosis is usually based on serological tests. however, cross-reactions may occur. western blotting allows the correct diagnosis.200818554395
[phagocytic functional and metabolic activities in the interaction with f. tularensis subspecies of various virulence].there is evidence that the facultatively intracellular pathogen affects the functional capacity of phagocytes, which is associated with their bactericidal against a tularemic microbe with varying phenotypic properties. the tularemic microbe of the subspecies francisella subsp. tularensis and f. tularensis subsp. mediaasiatica is shown to influence the phagocytic capacity of immunocompetent cells, resulting in incomplete phagocytosis. this is corroborated by the lower functional activity of neutr ...200818557359
genetic diversity of francisella tularensis subspecies holarctica strains isolated in japan.the recently developed mlva has high discriminatory power for the typing of individual strains or isolates of francisella tularensis. in the present study, mlva was applied to 33 japanese f. tularensis subspecies holarctica strains to examine the genetic diversity of f. tularensis isolated. among the seven vntr loci analyzed, ft-m2, ft-m10, and ft-m20 loci showed high genetic polymorphism in japanese strains, whereas ft-m3 was most variable in non-japanese strains. these results provide novel ex ...200818557897
application of carbohydrate microarray technology for the detection of burkholderia pseudomallei, bacillus anthracis and francisella tularensis antibodies.we developed a microarray platform by immobilizing bacterial 'signature' carbohydrates onto epoxide modified glass slides. the carbohydrate microarray platform was probed with sera from non-melioidosis and melioidosis (burkholderia pseudomallei) individuals. the platform was also probed with sera from rabbits vaccinated with bacillus anthracis spores and francisella tularensis bacteria. by employing this microarray platform, we were able to detect and differentiate b. pseudomallei, b. anthracis ...200818558401
identification of fevr, a novel regulator of virulence gene expression in francisella novicida.francisella tularensis infects wild animals and humans to cause tularemia. this pathogen targets the cytosol of macrophages, where it replicates using the genes in the francisella pathogenicity island (fpi). virulence gene regulation in francisella is complex, but transcriptional regulators mgla and sspa have been shown to regulate the expression of approximately 100 genes, including the entire fpi. we utilized a francisella novicida transposon mutant library to identify additional regulatory fa ...200818559431
kinetics of the immune response associated with tularemia: comparison of an enzyme-linked immunosorbent assay, a tube agglutination test, and a novel whole-blood lymphocyte stimulation test.we have developed and evaluated a novel and simplified whole-blood lymphocyte stimulation assay that focuses on the measurement of gamma interferon after 24 h of stimulation with whole-cell tularemia antigen and a tularemia enzyme-linked immunosorbent assay (elisa) based on highly purified lipopolysaccharide antigen. comparison of the kinetics of the two assays and those of the traditional tube agglutination test shows that the cellular immune response can be detected earlier by the lymphocyte s ...200818562568
characterization of fig operon mutants of francisella novicida u112.francisella species secrete a polycarboxylate siderophore that resembles rhizoferrin to acquire ferric iron. several of the francisella siderophore synthesis genes are contained in a fur-regulated operon (designated fig or fsl) comprised of at least seven orfs including fur. reverse transcriptase-pcr showed transcriptional linkage between figd and fige and between fige and figf. mutations were constructed in four of these orfs (figb, figc, figd, and fige) in francisella novicida u112. all four o ...200818564336
multiplex pathogen detection based on spatially addressable microarrays of barcoded resins.suspension microsphere immunoassays are rapidly gaining recognition in antigen identification and infectious disease biodetection due to their simplicity, versatility and high-throughput multiplex screening. we demonstrate a multiplex assay based on antibody-functionalized barcoded resins (bcrs) to identify pathogen antigens in complex biological fluids. the binding event of a particular antibody on given bead (fluorescence) and the identification of the specific pathogen agent (vibrational fing ...200818566958
diverse myeloid and lymphoid cell subpopulations produce gamma interferon during early innate immune responses to francisella tularensis live vaccine strain.francisella tularensis, a small gram-negative intracellular bacterium responsible for causing tularemia, is highly pathogenic and classified as a category a agent of bioterrorism. as for other intracellular pathogens, successful protective immune responses to francisella tularensis require rapid and efficient induction of gamma interferon (ifn-gamma) production. studies using intracellular bacteria such as listeria monocytogenes as well as francisella suggest that natural killer (nk) and t cells ...200818573901
a francisella tularensis schu s4 purine auxotroph is highly attenuated in mice but offers limited protection against homologous intranasal challenge.francisella tularensis is a gram-negative coccobacillus that causes the febrile illness tularemia. subspecies that are pathogenic for humans include those comprising the type a (subspecies tularensis) or type b (subspecies holarctica) biovars. an attenuated live vaccine strain (lvs) developed from a type b isolate has previously been used to vaccinate at-risk individuals, but offers limited protection against high dose (>1000 cfus) challenge with type a strains delivered by the respiratory route ...200818575611
mast cells inhibit intramacrophage francisella tularensis replication via contact and secreted products including il-4.francisella tularensis is an intracellular, gram-negative bacterium that is the causative agent of pulmonary tularemia. the pathogenesis and mechanisms related to innate resistance against f. tularensis are not completely understood. mast cells are strategically positioned within mucosal tissues, the major interface with the external environment, to initiate innate responses at the site of infection. mast cell numbers in the cervical lymph nodes and the lungs progressively increased as early as ...200818591675
outsmarting the host: bacteria modulating the immune response.pathogenic bacteria and their hosts have had a two-way conversation for millions of years. this interaction has led to many measure/counter-measure responses by the host and bacteria. the host immune response has developed many mechanisms to neutralize and remove pathogen bacteria. in turn pathogenic bacteria have developed mechanisms to alter and evade the host immune response. we will review some of the mechanisms utilized by bacteria to accomplish this goal. we will also examine the current s ...200818592144
the membrane form of tumor necrosis factor is sufficient to mediate partial innate immunity to francisella tularensis live vaccine strain.here we characterize francisella tularensis live vaccine strain (lvs) infection in total tumor necrosis factor (tnf) knockout (ko) mice and in transgenic mice expressing only the membrane form of tnf (memtnf). memtnf mice, but not tnf ko mice, survived low-dose, sublethal lvs infections. splenic nitric oxide production was impaired in infected memtnf mice and was absent in infected tnf ko mice. spleen cell production of interferon-gamma, rantes, and monocyte chemotactic protein-1 was elevated in ...200818593295
characterization of the francisella tularensis subsp. novicida type iv pilus.francisella tularensis causes the disease tularaemia. type iv pili (tfp) genes are present in the genomes of all f. tularensis subspecies. we show that the wild-type f. tularensis subsp. novicida expresses pilus fibres on its surface, and mutations in the tfp genes pilf and pilt disrupt pilus biogenesis. mutations in other tfp genes (pilq and pilg) do not eliminate pilus expression. a mutation in pile4 eliminates pilus expression, whereas mutations in the other pilin subunits pile1-3 and pile5 d ...200818599841
tularemia in range sheep: an overlooked syndrome?abortion and death caused by francisella tularensis were well recognized in range flocks of domestic sheep in idaho, montana, and wyoming in the first 6 decades of the 20th century. the current report describes 4 episodes of tularemia in 3 range flocks in wyoming and south dakota in 1997 and 2007 (1 flock was affected twice). flock owners reported that ticks were unusually numerous and commonly present on sheep during outbreaks. tularemia presented as late-term abortions (3 episodes) or listless ...200818599860
combating the threat of anthrax: a quantitative structure-activity relationship approach.bacterial agents or products more likely to be used as biological weapons of mass destruction are bacillus anthracis, francisella tularensis, yersinia pestis, and the neurotoxin of clostridium botulinum. anthrax is an acute infectious disease with a high mortality rate caused by bacillus anthracis, reinforcing the need for better adjunctive therapy and prevention strategies. in this paper, we developed 7 qsar models on penicillin-based inhibitors of the class a and b beta-lactamases from b. anth ...200818611038
generation and characterization of an attenuated mutant in a response regulator gene of francisella tularensis live vaccine strain (lvs).francisella tularensis is a zoonotic bacterium that must exist in diverse environments ranging from arthropod vectors to mammalian hosts. to better understand how virulence genes are regulated in these different environments, a transcriptional response regulator gene (genome locus ftl0552) was deleted in f. tularensis live vaccine strain (lvs). the ftl0552 deletion mutant exhibited slightly reduced rates of extracellular growth but was unable to replicate or survive in mouse macrophages and was ...200818613792
neisseria meningitidis porb, a toll-like receptor 2 ligand, improves the capacity of francisella tularensis lipopolysaccharide to protect mice against experimental tularemia.francisella tularensis causes severe pneumonia that can be fatal if it is left untreated. due to its potential use as a biological weapon, research is being conducted to develop an effective vaccine and to select and study adjuvant molecules able to generate a better and long-lasting protective effect. porb, a porin from neisseria meningitidis, is a well-established toll-like receptor 2 ligand and has been shown to be a promising vaccine adjuvant candidate due to its ability to enhance the t-cel ...200818614668
a bioinformatic approach to understanding antibiotic resistance in intracellular bacteria through whole genome analysis.intracellular bacteria survive within eukaryotic host cells and are difficult to kill with certain antibiotics. as a result, antibiotic resistance in intracellular bacteria is becoming commonplace in healthcare institutions. owing to the lack of methods available for transforming these bacteria, we evaluated the mechanisms of resistance using molecular methods and in silico genome analysis. the objective of this review was to understand the molecular mechanisms of antibiotic resistance through i ...200818619818
francisella tularensis: unravelling the secrets of an intracellular pathogen.francisella tularensis has been recognized as the causative agent of tularaemia for almost a century. since its discovery in 1911, it has been shown to infect a wide range of hosts, including humans. as early as the 1920s it was suggested to be an intracellular pathogen, but it has proven to be an enigmatic organism, whose interaction with the host has been difficult to elucidate, and we still have a very limited understanding of the molecular mechanisms of virulence. however, the recent availab ...200818628490
a european pathogenic microorganism proteome database: construction and maintenance.a relational database structure based on ms-access and mysql to store and manage proteomics data was established. this system may be used to publish two-dimensional electrophoretic proteomics data, and also may be accessed by external users who want to compare their own data with those in the databases. the maintenance of the database is managed centrally. the producers of proteomics data do not need to construct a database themselves. users can introduce mass spectra into the database, which al ...200218628887
temporal cytokine profiling of francisella tularensis-infected human peripheral blood mononuclear cells.francisella tularensis is an intracellular bacterium known to replicate in monocytes and macrophages and cause tularemia in humans. because of its infectious nature, f. tularensis is considered a biowarfare agent. early cytokine profiles of francisella-infected human peripheral blood mononuclear cells were evaluated.200818629413
adaptation of francisella tularensis to the mammalian environment is governed by cues which can be mimicked in vitro.the intracellular bacterium francisella tularensis survives in mammals, arthropods, and freshwater amoeba. it was previously established that the conventional media used for in vitro propagation of this microbe do not yield bacteria that mimic those harvested from infected mammals; whether these in vitro-cultivated bacteria resemble arthropod- or amoeba-adapted francisella is unknown. as a foundation for our goal of identifying f. tularensis outer membrane proteins which are expressed during mam ...200818644878
molecular method for discrimination between francisella tularensis and francisella-like endosymbionts.environmental studies on the distribution of francisella spp. are hampered by the frequency of francisella-like endosymbionts that can produce a misleading positive result. a new, efficient molecular method for detection of francisella tularensis and its discrimination from francisella-like endosymbionts, as well as two variants associated with human disease (unusual f. tularensis strain fnsp1 and f. tularensis subsp. novicida-like strain 3523), is described. the method is highly specific and se ...200818650358
[specific effect of attenuated strain of francisella tularensis on the development of radiation induced lesions in experimental animals and effictiveness of antibacterial therapy for lesions induced by radiation combined with virulemt strain of the bacteria].for study of the effects of whole-body gamma-radiation (1 and 4 gy) on the response of the body to administration of vaccines and virulent strains of tularemia 206 outbred white mice were used. the results of the study shown that the administration of attenuated bacterial cells in 5 days after exposure to radiation (1 and 4 gy) caused more severe post-radiation effects and the increase in the number of died animals. the severity of the disease was less if mice were vaccinated in 26 days after ir ...200818666584
transcriptional profiling of francisella tularensis infected peripheral blood mononuclear cells: a predictive tool for tularemia.in this study, we analyzed temporal gene expression patterns in human peripheral blood mononuclear cells (pbmcs) infected with the francisella tularensis live vaccine strain from 1 to 24 h utilizing a whole human affymetrix gene chip. we found that a considerable number of induced genes had similar expression patterns and functions as reported previously for gene expression profiling in patients with ulceroglandular tularemia. among the six uniquely regulated genes reported for tularemia patient ...200818680519
nodular lymphangitis: a distinctive clinical entity with finite etiologies.nodular lymphangitis, characterized by inflammatory nodules along the lymphatics draining a primary skin infection, most commonly follows superficial inoculation with sporothrix schenckii, nocardia brasiliensis, mycobacterium marinum, leishmania (viannia) panamensis/guyanensis, and francisella tularensis. epidemiologic context, clinical presentation, and presumed incubation period help to predict the specific etiologic microorganism. sporotrichosis, often occurring in gardeners, remains the most ...200818687205
an improved vaccine for prevention of respiratory tularemia caused by francisella tularensis schus4 strain.vaccination of mice with francisella tularensis live vaccine strain (lvs) mutants described so far have failed to induce protection in c57bl/6 mice against challenge with the virulent strain f. tularensis schus4. we have previously reported that a mutant of f. tularensis lvs deficient in iron superoxide dismutase (sodb(ft)) is hypersensitive to oxidative stress and attenuated for virulence in mice. herein, we evaluated the efficacy of this mutant as a vaccine candidate against respiratory tulare ...200818692537
microarray analysis of human monocytes infected with francisella tularensis identifies new targets of host response subversion.francisella tularensis is a gram-negative facultative bacterium that causes the disease tularemia, even upon exposure to low numbers of bacteria. one critical characteristic of francisella is its ability to dampen or subvert the host immune response. in order to help understand the mechanisms by which this occurs, we performed affymetrix microarray analysis on transcripts from blood monocytes infected with the virulent type a schu s4 strain. results showed that expression of several host respons ...200818698339
tlr4-mediated activation of dendritic cells by the heat shock protein dnak from francisella tularensis.francisella tularensis is the causative agent of tularemia, a severe, debilitating disease of humans and other mammals. as this microorganism is also classified as a "category-a pathogen" and a potential biowarfare agent, there is a need for an effective vaccine. several antigens of f. tularensis, including the heat shock protein dnak, have been proposed for use in a potential subunit vaccine. in this study, we characterized the innate immune response of murine bone marrow-derived dendritic cell ...200818708593
cytokine response in balb/c mice infected with francisella tularensis lvs and the pohang isolate.we investigated the immune response induced by the francisella (f.) tularensis live vaccine strain (lvs) and the pohang isolate. after the balb/c mice were infected intradermally (i.d) with 2 x 10(4) cfu of f. tularensis lvs and pohang, respectively, their blood and organs were collected at different times; 0, 3, 6, 24, 72, 96, 120 and 168 h after infection. using these samples, rt-pcr and elisa analysis were carried out for the comparative study of the cytokines, including tnf-alpha, inf-gamma, ...200818716452
targeting qsec signaling and virulence for antibiotic development.many bacterial pathogens rely on a conserved membrane histidine sensor kinase, qsec, to respond to host adrenergic signaling molecules and bacterial signals in order to promote the expression of virulence factors. using a high-throughput screen, we identified a small molecule, led209, that inhibits the binding of signals to qsec, preventing its autophosphorylation and consequently inhibiting qsec-mediated activation of virulence gene expression. led209 is not toxic and does not inhibit pathogen ...200818719281
tularemia.tularemia is a rare zoonotic infection caused by the bacterium francisella tularensis. the disease is endemic in north america and parts of europe and asia. arthropods (ticks and deer flies) are the main transmission vector, and small animals (rabbits, hares, and muskrats) serve as reservoir hosts. the clinical presentation depends on the bacterial subspecies and the route of infection. recent world events have led to a new recognition of f tularensis as a viable agent of bioterrorism, which has ...200818755386
tularemia in a park, philadelphia, pennsylvania. 200818760026
ripa, a cytoplasmic membrane protein conserved among francisella species, is required for intracellular survival.francisella tularensis is a highly virulent bacterial pathogen that invades and replicates within numerous host cell types, including macrophages and epithelial cells. in an effort to better understand this process, we screened a transposon insertion library of the f. tularensis live vaccine strain (lvs) for mutant strains that invaded but failed to replicate within alveolar epithelial cell lines. one such strain isolated from this screen contained an insertion in the gene ftl_1914, which is con ...200818765722
francisella tularensis live vaccine strain induces macrophage alternative activation as a survival mechanism.francisella tularensis (ft), the causative agent of tularemia, elicits a potent inflammatory response early in infection, yet persists within host macrophages and can be lethal if left unchecked. we report in this study that ft live vaccine strain (lvs) infection of murine macrophages induced tlr2-dependent expression of alternative activation markers that followed the appearance of classically activated markers. intraperitoneal infection with ft lvs also resulted in induction of alternatively a ...200818768873
lymphotoxin-alpha plays only a minor role in host resistance to respiratory infection with virulent type a francisella tularensis in mice.this study examined the role of lymphotoxin (lt)-alpha in host defense against airborne infection with francisella tularensis, a gram-negative facultative intracellular bacterium and the causative agent of tularemia. following a low-dose aerosol infection with the highly virulent type a strain of f. tularensis, mice deficient in ltalpha (ltalpha-/-) consistently harbored approximately 10-fold fewer bacteria in their spleens at day 2 and 10-fold more bacteria in their lungs at day 4 than ltalpha+ ...200818769490
a novel receptor - ligand pathway for entry of francisella tularensis in monocyte-like thp-1 cells: interaction between surface nucleolin and bacterial elongation factor tu.francisella tularensis, the causative agent of tularemia, is one of the most infectious human bacterial pathogens. it is phagocytosed by immune cells, such as monocytes and macrophages. the precise mechanisms that initiate bacterial uptake have not yet been elucidated. participation of c3, cr3, class a scavenger receptors and mannose receptor in bacterial uptake have been already reported. however, contribution of an additional, as-yet-unidentified receptor for f. tularensis internalization has ...200818789156
detection of francisella tularensis in ticks and identification of their genotypes using multiple-locus variable-number tandem repeat analysis.tularemia was reported in china over 50 years ago, however, many epidemical characteristics remain unclear. in the present study, the prevalence of francisella tularensis in ticks was investigated during an epidemiological surveillance in china and then we measured their genetic diversity by conducting multiple-locus variable- number tandem repeat analysis (mlva).200818798995
tularemia in germany: the tip of the iceberg?tularemia is a rare, notifiable zoonosis in germany. since november 2004, several lines of evidence including outbreaks in humans or animals and confirmed infections in indigenous hare and rodent populations have indicated a re-emergence of tularemia in different german federal states. unfortunately, reliable basic information on the seroprevalence in different geographical regions, permitting the identification of risk factors, does not exist. combining a sensitive screening assay with a highly ...200918808726
an intracellularly inducible gene involved in virulence and polyphosphate production in francisella.francisella tularensis is an intracellular pathogen capable of multiplying to high levels in macrophages. by protein analysis, only a few proteins have been shown previously to be expressed at high levels in macrophages relative to bacteria grown in culture media. to identify additional genes that show increased expression during intracellular growth, we developed a plasmid for use in francisella based on the induction of expression of green fluorescent protein. clones of f. tularensis subsp. no ...200818809544
tularemia in children.tularemia, an infection caused by the coccobacilus francisella tularensis, can be a difficult disease process to diagnose and treat. the aim of this study was to evaluate an epidemic of tularemia in bursa.200818810348
effective host response to francisella tularensis requires functional mast cells.evaluation of: ketavarapu jm, rodriguez ar, yu j et al.: mast cells inhibit intramacrophage francisella tularensis replication via contact and secreted products including il-4. proc. natl acad. sci. usa 105(27), 9313-9318 (2008). the intracellular pathogen francisella tularensis is a highly infectious organism that infects cells of the immune system. mast cells have been known for their role in anaphylaxis, although they are also important for their ability to aid in the defense against pathogen ...200818811234
[interaction of s- and r-lipopolysaccharides of francisella tularensis with lypopolysaccharide-binding protein of human serum].investigation of ability of francisella tularensis s- and r-lypopolysaccharide (lps) preparations as well as the live bacteria with different chemotypes to interact with human lypopolysaccharide-binding protein (lbp) was carried out. it was found that lps preparations derived from virulent(s-lps) or isogenic avirulent mutant (r-lps) strains of f. tularensis had markedly lower affinity to lbp as compared with typical s-lps of salmonella abortus and r-lps of yersinia pestis. it was shown that r-lp ...200818819401
[temperate legionella bacteriophage: discovery and characteristics].for the first time, temperate legionella bacteriophage was isolated from organs of guinea pig infected with philadelphia 1 strain of legionella pneumophila. negative colonies of bactriophage from 1.5 to 2.5 mm in diameter were detected. central part of them was transparent and surrounded by peripheral zone of partial lysis. electron microscopy showed that corpuscles of the phage consist from multifaceted elongated head of stretched hexagonal form and short tail. the bacteriophage lyzed bacteria, ...200818819413
evasion of complement-mediated lysis and complement c3 deposition are regulated by francisella tularensis lipopolysaccharide o antigen.the bacterium francisella tularensis (ft) is a potential weapon of bioterrorism when aerosolized. macrophage infection is necessary for disease progression and efficient phagocytosis by human macrophages requires serum opsonization by complement. microbial complement activation leads to surface deposition of a highly regulated protein complex resulting in opsonization or membrane lysis. the nature of complement component c3 deposition, i.e., c3b (opsonization and lysis) or c3bi (opsonization onl ...200818832715
genetic dissection of the francisella novicida restriction barrier.francisella tularensis is the causative agent of tularemia and is a category a select agent. francisella novicida, considered by some to be one of four subspecies of f. tularensis, is used as a model in pathogenesis studies because it causes a disease similar to tularemia in rodents but is not harmful to humans. f. novicida exhibits a strong restriction barrier which reduces the transformation frequency of foreign dna up to 10(6)-fold. to identify the genetic basis of this barrier, we carried ou ...200818835994
humoral and cell-mediated immunity to the intracellular pathogen francisella tularensis.summary: francisella tularensis can cause fatal respiratory tularemia in humans and animals and is increasingly being isolated in the united states and several european countries. the correlates of protective immunity against this intracellular bacterium are not known, and currently there are no licensed vaccines available for human use. cell-mediated immunity has long been believed to be critical for protection, and the importance of humoral immunity is also now recognized. furthermore, synergy ...200818837786
global transcriptional response to mammalian temperature provides new insight into francisella tularensis pathogenesis.after infecting a mammalian host, the facultative intracellular bacterium, francisella tularensis, encounters an elevated environmental temperature. we hypothesized that this temperature change may regulate genes essential for infection.200818842136
development and application of the active surveillance of pathogens microarray to monitor bacterial gene flux.human and animal health is constantly under threat by emerging pathogens that have recently acquired genetic determinants that enhance their survival, transmissibility and virulence. we describe the construction and development of an active surveillance of pathogens (asp) oligonucleotide microarray, designed to 'actively survey' the genome of a given bacterial pathogen for virulence-associated genes.200818844996
the early phagosomal stage of francisella tularensis determines optimal phagosomal escape and francisella pathogenicity island protein expression.francisella tularensis is an intracellular pathogen that can survive and replicate within macrophages. following phagocytosis and transient interactions with the endocytic pathway, f. tularensis rapidly escapes from its original phagosome into the macrophage cytoplasm, where it eventually replicates. to examine the importance of the nascent phagosome for the francisella intracellular cycle, we have characterized early trafficking events of the f. tularensis subsp. tularensis strain schu s4 in a ...200818852245
infected-host-cell repertoire and cellular response in the lung following inhalation of francisella tularensis schu s4, lvs, or u112.francisella tularensis causes systemic disease in humans and other mammals, with high morbidity and mortality associated with inhalation-acquired infection. f. tularensis is a facultative intracellular pathogen, but the scope and significance of cell types infected during disease is unknown. using flow cytometry, we identified and quantified infected-cell types and assessed the impact of infection on cell populations following inhalation of f. tularensis strains u112, lvs, and schu s4. initially ...200818852251
artificial plasmid engineered to simulate multiple biological threat agents.the objective of this study was to develop a non-virulent simulant to replace several virulent organisms during the development of detection and identification methods for biological threat agents. we identified and selected specific genes to detect yersinia pestis, francisella tularensis, burkholderia mallei, burkholderia pseudomallei, rickettsia sp., coxiella burnetii, brucella sp., enterohemorrhagic escherichia coli o157:h7, bacillus anthracis, and variola (smallpox) virus. we then designed a ...200918923830
re-assembly of the genome of francisella tularensis subsp. holarctica osu18.francisella tularensis is a highly infectious human intracellular pathogen that is the causative agent of tularemia. it occurs in several major subtypes, including the live vaccine strain holarctica (type b). f. tularensis is classified as category a biodefense agent in part because a relatively small number of organisms can cause severe illness. three complete genomes of subspecies holarctica have been sequenced and deposited in public archives, of which osu18 was the first and the only strain ...200818927608
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 ...200918929413
levofloxacin rescues mice from lethal intra-nasal infections with virulent francisella tularensis and induces immunity and production of protective antibody.the ability to protect mice against respiratory infections with virulent francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. in this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with f. tularensis schu s4. we show that mice infected with a lethal dose of schu s4, via an intra-nasal challenge, could be protected with levoflo ...200818930100
detection of a novel francisella in dermacentor reticulatus: a need for careful evaluation of pcr-based identification of francisella tularensis in eurasian ticks.francisella tularensis, the causative agent of tularemia, has been detected in ixodid ticks in some regions of north america, europe, and asia. in the present study, 245 dermacentor reticulatus, 211 ixodes ricinus, and 194 haemaphysalis concinna adults from hungary were tested for the presence of f. tularensis by polymerase chain reaction (pcr) assays based on 16s ribosomal rna (16s rdna) and t-cell epitope of a francisella membrane protein (tul4). no francisella-specific amplification products ...200818945184
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 ...200918946633
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.200918950590
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 ...200918954971
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 ...200918955478
repeatability and pattern recognition of bacterial fatty acid profiles generated by direct mass spectrometric analysis of in situ thermal hydrolysis/methylation of whole cells.direct ci mass spectrometry profiling of fatty acid methyl esters (fames) from in situ thermal hydrolysis/methylation (thm) of whole bacterial cells with tetramethylammonium hydroxide (tmah) has been demonstrated as a potential method for real time and fieldable detection/identification of microorganisms. bacillus anthracis (ames), yersinia pestis (nair. kenya), vibrio cholerae (e1 tor), brucella melitensis (abortus wild) and francisella tularensis (lvs vaccine) were profiled by this method duri ...200318968943
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 ...200918974037
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 ...200918981246
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 ...200918981253
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 ...200918992838
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 ...200919001470
[participation of murine rodents in circulation of agents of tularemia and hemorrhagic fever in kola peninsula].results of virological and bacteriological studies of wild mammals of 11 species from rodentia and cricetidae genuses during epizootic period (spring-autumn 2006-2007) in murmansk region are presented. the number of red-baked mice (clethrionomys) and common vole (microtus) was rising. antigen of hemorrhagic fever with renal syndrome virus as well as tularemia pathogen were found in background rodent species.200819004288
inhibition of expression in escherichia coli of a virulence regulator mglb of francisella tularensis using external guide sequence technology.external guide sequences (egss) have successfully been used to inhibit expression of target genes at the post-transcriptional level in both prokaryotes and eukaryotes. we previously reported that egs accessible and cleavable sites in the target rnas can rapidly be identified by screening random egs (regs) libraries. here the method of screening regs libraries and a partial rnase t1 digestion assay were used to identify sites accessible to egss in the mrna of a global virulence regulator mglb fro ...200819005569
re-emergence of tularemia in germany: presence of francisella tularensis in different rodent species in endemic areas.tularemia re-emerged in germany starting in 2004 (with 39 human cases from 2004 to 2007) after over 40 years of only sporadic human infections. the reasons for this rise in case numbers are unknown as is the possible reservoir of the etiologic agent francisella (f.) tularensis. no systematic study on the reservoir situation of f. tularensis has been published for germany so far.200819014635
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 ...200919015321
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.200919018964
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 ...200919022323
interrelationship between dendritic cell trafficking and francisella tularensis dissemination following airway infection.francisella tularensis, the etiological agent of the inhalation tularemia, multiplies in a variety of cultured mammalian cells. nevertheless, evidence for its in vivo intracellular residence is less conclusive. dendritic cells (dc) that are adapted for engulfing bacteria and migration towards lymphatic organs could serve as potential targets for bacterial residence and trafficking. here, we focus on the in vivo interactions of f. tularensis with dc following airway infection of mice. lethal airw ...200819023422
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 ...200919029814
thermal resistance of francisella tularensis in infant formula and fruit juices.francisella tularensis is a gram-negative bacterium that can cause gastrointestinal or oropharyngeal tularemia from ingestion of contaminated food or water. despite the potential for accidental or intentional contamination of foods with f. tularensis, little information exists on the thermal stability of this organism in food matrices. in the present study, the thermal resistance of the live vaccine strain of f. tularensis in four food products (liquid infant formula, apple juice, mango juice, a ...200819044262
multiple francisella tularensis subspecies and clades, tularemia outbreak, utah.in july 2007, a deer fly-associated outbreak of tularemia occurred in utah. human infections were caused by 2 clades (a1 and a2) of francisella tularensis subsp. tularensis. lagomorph carcasses from the area yielded evidence of infection with a1 and a2, as well as f. tularensis subsp. holarctica. these findings indicate that multiple subspecies and clades can cause disease in a localized outbreak of tularemia.200819046524
francisella novicida bacteremia, thailand.we report isolation of francisella novicida-causing bacteremia in a woman from thailand who was receiving chemotherapy for ovarian cancer. the organism was isolated from blood cultures and identified by 16s rdna and ppiase gene analyses. diagnosis and treatment were delayed due to unawareness of the disease in this region.200819046526
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 ...200919047404
discrimination between biothreat agents and 'near neighbor' species using a resequencing array.timely identification of biothreat organisms from large numbers of clinical or environmental samples in potential outbreak or attack scenario is critical for effective diagnosis and treatment. this study aims to evaluate the potential of resequencing arrays for this purpose. albeit suboptimal, this report demonstrated that respiratory pathogen microarray version 1 can identify bacillus anthracis, francisella tularensis, yersinia pestis and distinguish them from benign 'near neighbor' species in ...200819049648
francisella genes required for replication in mosquito cells.francisella tularensis, a potential bioterrorism agent, is transmitted by arthropod vectors and causes tularemia in many mammals, including humans. francisella novicida causes disease with similar pathology in mice. we show that f. novicida invades hemocyte-like cells of the sualb cell line derived from anopheles gambiae and replicates vigorously within these cells. we used transposon knockouts of single genes of f. novicida to show that bacterial growth within these insect cells is dependent on ...200819058636
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 ...200919067747
rapid dissemination of francisella tularensis and the effect of route of infection.francisella tularensis subsp. tularensis is classified as a category a bioweapon that is capable of establishing a lethal infection in humans upon inhalation of very few organisms. however, the virulence mechanisms of this organism are not well characterized. francisella tularensis subsp. novicida, which is an equally virulent subspecies in mice, was used in concert with a micropet scanner to better understand its temporal dissemination in vivo upon intranasal infection and how such disseminatio ...200819068128
diagnosis of tularemia using piezoelectric biosensor technology.a piezoelectric immunosensor for indirect diagnosis of tularemic infection in mouse serum was developed. francisella tularensis lvs antigen was covalently immobilized on the sensing surface using cystamine and glutaraldehyde for activation and modification of the gold electrode. the normal mouse serum (nms) and serum prepared from mice immunized by escherichia coli were used as negative controls providing signal of 28hz during a 5min interaction. the tularemic infectious (immunized) mouse serum ...200719071403
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.200919074656
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 ...200919074661
comparison of the new inodiag automated fluorescence multiplexed antigen microarray to the reference technique in the serodiagnosis of atypical bacterial pneumonia.the aetiological diagnosis of pneumonia depends largely on culture-, antigen- or pcr-based tests. atypical agents of pneumonia include coxiella burnetii, chlamydophila pneumoniae, chlamydia psittaci, legionella pneumophila, francisella tularensis and mycoplasma pneumoniae. in these cases, serological tests are commonly used for diagnosis. all of the above species were comparatively screened for by using the inodiag multiplexed automatic immunofluorescence assay and established reference techniqu ...200819076843
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. ...200919084603
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 ...200919095065
does the trojan horse have an achilles' heel? 200919118310
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 ...200919119037
Refresh
firstprev
...11121314151617181920...
nextlast
Displaying items 1601 - 1700 of 2254