Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
fragmentation-free lc-ms can identify hundreds of proteins.one of the most common approaches for large-scale protein identification is lc, followed by ms. if more than a few proteins are to be identified, the additional fragmentation of individual peptides has so far been considered as indispensable, and thus, the associated costs, in terms of instrument time and infrastructure, as unavoidable. here, we present evidence to the contrary. using a combination of (i) highly accurate and precise mass measurements, (ii) modern retention time prediction, and ( ...201021182191
iron content differs between francisella tularensis subspecies tularensis and subspecies holarctica strains and correlates to their susceptibility to h(2)o(2)-induced killing.francisella tularensis, the causative agent of tularemia, is one of the most infectious bacterial pathogens known and is classified as a category a select agent and a facultative intracellular bacterium. why f. tularensis subsp. tularensis causes a more severe form of tularemia than f. tularensis subsp. holarctica does is not known. in this study, we have identified prominent phenotypic differences between the subspecies, since we found that f. tularensis subsp. tularensis strains contained less ...201021189323
monitoring the survival of fish-pathogenic francisella in water microcosms.in this report, the survival behaviour of fish pathogenic francisella in water microcosms was investigated under laboratory conditions. two isolates of francisella noatunensis (ncimb14265(t) and pq 1106), from fish held in seawater and freshwater, were inoculated into natural (nonsterile) and sterile sea- and freshwater microcosms, respectively, and monitored under different temperature conditions (4, 8 and 12 °c) over a period of 60 days. the culturability of the strains was inversely related t ...201020977492
determination of francisella tularensis acpb acid phosphatase substrate preferences.the francisella species encode 4 main acid phosphatases (acp) that are potentially involved in pathogenesis through currently unknown mechanisms. only 2 of these enzymes, acpa and acpc, have been biochemically characterized to date. in this work we describe the catalytic properties of francisella tularensis acpb utilizing an array of 120 phosphorylated substrates. in contrast to most acid phosphatases, the purified enzyme showed a narrow range of substrate preferences, with the highest affinity ...201021042033
structure of the francisella tularensis enoyl-acyl carrier protein reductase (fabi) in complex with nad(+) and triclosan.enoyl-acyl carrier protein reductase (fabi) catalyzes the last rate-limiting step in the elongation cycle of the fatty-acid biosynthesis pathway and has been validated as a potential antimicrobial drug target in francisella tularensis. the development of new antibiotic therapies is important both to combat potential drug-resistant bioweapons and to address the broader societal problem of increasing antibiotic resistance among many pathogenic bacteria. the crystal structure of fabi from f. tulare ...201021045289
comparative proteomic profiling of culture filtrate proteins of less and highly virulent francisella tularensis strains.the facultative intracellular bacterium francisella tularensis is the causal agent of the serious infectious disease tularemia. despite the dynamic progress, which has been made in last few years, important questions regarding francisella pathogenicity still remain to be answered. generally, secreted proteins play an important role in pathogenicity of intracellular microbes. in this study, we investigated the protein composition of the culture filtrate proteins of highly virulent f. tularensis s ...201021061425
[an oropharyngeal tularemia case diagnosed by the isolation of francisella tularensis on human blood agar].tularemia which is a multisystem disease of humans and some animals, is endemic in north america, some parts of europe and asia. the causative agent, francisella tularensis, is a fastidious gram-negative, intracellular bacterium which requires supplementation with sulphydryl compounds (cysteine, cystine, thiosulphate, isovitalex) for growth on common laboratory media. in this report, a case of oropharyngeal tularemia diagnosed by the isolation of the causative agent on non-selective-common micro ...201021063979
identification of small rnas in francisella tularensis.regulation of bacterial gene expression by small rnas (srnas) have proved to be important for many biological processes. francisella tularensis is a highly pathogenic gram-negative bacterium that causes the disease tularaemia in humans and animals. relatively little is known about the regulatory networks existing in this organism that allows it to survive in a wide array of environments and no srna regulators have been identified so far.201021067590
genetic identification of unique immunological responses in mice infected with virulent and attenuated francisella tularensis.francisella tularensis is a category a select agent based on its infectivity and virulence but disease mechanisms in infection remain poorly understood. murine pulmonary models of infection were therefore employed to assess and compare dissemination and pathology and to elucidate the host immune response to infection with the highly virulent type a f. tularensis strain schu4 versus the less virulent type b live vaccine strain (lvs). we found that dissemination and pathology in the spleen was sig ...201021070859
coexistence of emerging bacterial pathogens in ixodes ricinus ticks in serbia.the list of tick-borne pathogens is long, varied and includes viruses, bacteria, protozoa and nematodes. as all of these agents can exist in ticks, their co-infections have been previously reported. we studied co-infections of emerging bacterial pathogens (borrelia burgdorferi sensu lato, anaplasma phagocytophilum and francisella tularensis) in ixodes ricinus ticks in serbia. using pcr technique, we detected species-specific sequences, rrf-rrl rdna intergenic spacer for b. burgdorferi s.l., p44/ ...201021073144
the calcineurin inhibitor rcan1 is involved in cultured macrophage and in vivo immune response.studies on the role of regulator of calcineurin 1 (rcan1) in immunity are limited, but have demonstrated an involvement in t-lymphocyte function. here, we expand these studies to macrophages and in vivo infection. the treatment of raw and primary mouse macrophages with lipopolysaccharide from escherichia coli strongly induced rcan1 isoform 4 (rcan1-4), but not isoform 1. rcan1-4 induction involved calcium, calcineurin, and reactive oxygen species. subsequent analysis with whole bacteria includin ...201021073546
francisella tularensis schu s4 o-antigen and capsule biosynthesis gene mutants induce early cell death in human macrophages.francisella tularensis is capable of rampant intracellular growth and causes a potentially fatal disease in humans. whereas many mutational studies have been performed with avirulent strains of francisella, relatively little has been done with strains that cause human disease. we generated a near-saturating transposon library in the virulent strain schu s4, which was subjected to high-throughput screening by transposon site hybridization through primary human macrophages, negatively selecting 20 ...201021078861
a bacterial two-hybrid system that utilizes gateway cloning for rapid screening of protein-protein interactions.comprehensive clone sets representing the entire genome now exist for a large number of organisms. the gateway entry clone sets are a particularly useful means to study gene function, given the ease of introduction into any gateway-suitable destination vector. we have adapted a bacterial two-hybrid system for use with gateway entry clone sets, such that potential interactions between proteins encoded within these clone sets can be determined by new destination vectors. we show that utilizing the ...201021091448
phosphatidylinositol 3-kinase activation attenuates the tlr2-mediated macrophage proinflammatory cytokine response to francisella tularensis live vaccine strain.an inadequate innate immune response appears to contribute to the virulence of francisella tularensis following pulmonary infection. studies in mice suggest that this poor response results from suppression of proinflammatory cytokine production early during infection, but the mechanisms involved are not understood. pi3k is known to regulate proinflammatory cytokine expression, but its exact role (positive versus negative) is controversial. we sought to clarify the role of pi3k in regulating proi ...201021098227
detection of a novel subspecies of francisella noatunensis as endosymbiont of the ciliate euplotes raikovi.francisella are facultative intracellular bacteria causing severe disease in a broad range of animals. two species are notable: francisella tularensis, the causative organism of tularemia and a putative warfare agent, and francisella noatunensis, an emerging fish pathogen causing significant losses in wild and farmed fish. although various aspects of francisella biology have been intensively studied, their natural reservoir in periods between massive outbreaks remains mysterious. protists have b ...201021110016
quantification of the relationship between bacterial kinetics and host response for monkeys exposed to aerosolized francisella tularensis.francisella tularensis can be disseminated via aerosols, and once inhaled, only a few microorganisms may result in tularemia pneumonia. effective responses to this threat depend on a thorough understanding of the disease development and pathogenesis. in this study, a class of time-dose-response models was expanded to describe quantitatively the relationship between the temporal probability distribution of the host response and the in vivo bacterial kinetics. an extensive literature search was co ...201021115714
rabbit tularemia and hepatic coccidiosis in wild rabbit. 201021122253
attenuated response of aged mice to respiratory francisella novicida is characterized by reduced cell death and absence of subsequent hypercytokinemia.pneumonia and pulmonary infections are major causes of mortality among the growing elderly population. age associated attenuations of various immune parameters, involved with both innate and adaptive responses are collectively known as immune senescence. these changes are likely to be involved with differences in host susceptibility to disease between young and aged individuals.201021124895
molecular diagnosis of francisellosis, a systemic granulomatous inflammatory disease in atlantic cod, gadus morhua l.a pcr-based assay for the detection of francisella noatunensis causing francisellosis in atlantic cod, gadus morhua has been developed. seven sets of primers targeting the flanking regions of the genes (rpoa, sdha, atpa, rpob, pgm, groel and 16s rrna) of the pathogen were designed. among the primers, groel was found to be the most suitable gene candidate for detecting the pathogen, due to its high sensitivity at various annealing temperatures and specificity in detection. the detection limit of ...201021125329
protection afforded by fluoroquinolones in animal models of respiratory infections with bacillus anthracis, yersinia pestis, and francisella tularensis.successful treatment of inhalation anthrax, pneumonic plague and tularemia can be achieved with fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. bacillus anthracis ames, yersinia pestis co92, and francisella tularensis schu s4 have equivalent susceptibility in vitro to ciprofloxacin and levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited informat ...201021127743
the intracellular lifestyle of francisella noatunensis in atlantic cod (gadus morhua l.) leucocytes.francisella noatunensis causes the systemic granulomatous inflammatory disease, francisellosis in cod. little is known about the lifestyle of this facultative intracellular bacterium within cod leucocytes. we have examined the interaction of this bacterium with phagocytic cells isolated from cod with emphasis on monocytes, macrophages, neutrophils and phagocytic b-cells. it is clear from confocal microscopy sections through adherent cell preparations that numerous bacteria were located intracell ...201021129488
survival of francisella tularensis type a in brackish-water.martha's vineyard (mv), massachusetts has been the location of two outbreaks of pneumonic tularemia; landscaping activities have been associated with risk, suggesting environmental inhalation exposure. we determined whether salinity or other components of brackish-water present in a location with endemic tularemia may prolong survival of f. tularensis. in addition, we demonstrate for the first time that f. tularensis type a appears similar to type b with respect to environmental stability. the r ...201021136042
comparative proteomic profiling of culture filtrate proteins of less and highly virulent francisella tularensis strains.the facultative intracellular bacterium francisella tularensis is the causal agent of the serious infectious disease tularemia. despite the dynamic progress, which has been made in last few years, important questions regarding francisella pathogenicity still remain to be answered. generally, secreted proteins play an important role in pathogenicity of intracellular microbes. in this study, we investigated the protein composition of the culture filtrate proteins of highly virulent f. tularensis s ...201021136602
reciprocal analysis of francisella novicida infections of a drosophila melanogaster model reveal host-pathogen conflicts mediated by reactive oxygen and imd-regulated innate immune response.the survival of a bacterial pathogen within a host depends upon its ability to outmaneuver the host immune response. thus, mutant pathogens provide a useful tool for dissecting host-pathogen relationships, as the strategies the microbe has evolved to counteract immunity reveal a host's immune mechanisms. in this study, we examined the pathogen francisella novicida and identified new bacterial virulence factors that interact with different parts of the drosophila melanogaster innate immune system ...201020865166
simultaneous pathogen detection and antibiotic resistance characterization using snp-based multiplexed oligonucleotide ligation-pcr (mol-pcr).extensive use of antibiotics in both public health and animal husbandry has resulted in rapid emergence of antibiotic resistance in almost all human pathogens, including biothreat pathogens. antibiotic resistance has thus become a major concern for both public health and national security. we developed multiplexed assays for rapid, simultaneous pathogen detection and characterization of ciprofloxacin and doxycycline resistance in bacillus anthracis, yersinia pestis, and francisella tularensis. t ...201020865530
analysis of lipids from crude lung tissue extracts by desorption electrospray ionization mass spectrometry and pattern recognition.a method is described using desorption electrospray ionization (desi) mass spectrometry (ms) to obtain phospholipid mass spectral profiles from crude lung tissue extracts. the measured desi mass spectral lipid fingerprints were then analyzed by unsupervised learning principal components analysis (pca). this combined approach was used to differentiate the effect(s) of two vaccination routes on lipid composition in mouse lungs. specifically, the two vaccination routes compared were intranasal (i.n ...201020868645
[preparation of magnetic latexes and their use for the immunodetection of microbial antigens].the possibility of detecting antigens of plague, tularemia, and brucellosis microbes with magnetic latex (ml)-based test systems has been demonstrated. mls were prepared from latexes (polyacroleine microspheres, 1.2-1.8 +/- 0.1 microm) by exposing the particles to a 25-35%-solution of ferrous sulfate for 0.5 h and then to a 15-25%-aqueous solution of ammonia for 0.5 h in a 100 degrees c water bath and dehydrating after each operation. the possibility of preparing magnetic latex immunosorbents (m ...201020873177
molecular detection of persistent francisella tularensis subspecies holarctica in natural waters.tularemia, caused by the bacterium francisella tularensis, where f. tularensis subspecies holarctica has long been the cause of endemic disease in parts of northern sweden. despite this, our understanding of the natural life-cycle of the organism is still limited. during three years, we collected surface water samples (n = 341) and sediment samples (n = 245) in two areas in sweden with endemic tularemia. real-time pcr screening demonstrated the presence of f. tularenis lpna sequences in 108 (32% ...201020885922
effects of the putative transcriptional regulator iclr on francisella tularensis pathogenesis.francisella tularensis is a highly virulent gram-negative bacterium and is the etiological agent of the disease tularemia. iclr, a presumed transcriptional regulator, is required for full virulence of the animal pathogen, f. tularensis subspecies novicida u112 (53). in this study, we investigated the contribution of iclr to the intracellular growth, virulence, and gene regulation of human pathogenic f. tularensis subspecies. deletion of iclr from the live vaccine strain (lvs) and schus4 strain o ...201020921148
deletion of ripa alleviates suppression of the inflammasome and mapk by francisella tularensis.francisella tularensis is a facultative intracellular pathogen and potential biothreat agent. evasion of the immune response contributes to the extraordinary virulence of this organism although the mechanism is unclear. whereas wild-type strains induced low levels of cytokines, an f. tularensis ripa deletion mutant (lvsδripa) provoked significant release of il-1β, il-18, and tnf-α by resting macrophages. il-1β and il-18 secretion was dependent on inflammasome components pyrin-caspase recruitment ...201020921527
a review of sentinel laboratory performance: identification and notification of bioterrorism agents.the anthrax incident of 2001 in the united states prompted the college of american pathologists (cap), the association of public health laboratories, and the centers for disease control and prevention to develop exercises for laboratory response network (lrn) sentinel laboratories.201020923306
[tularemia]. 201020942053
case records of the massachusetts general hospital. case 31-2010. a 29-year-old woman with fever after a cat bite. 201020942673
enhancement of deoxyribonucleic acid microarray performance using post-hybridization signal amplification.microarray performance depends upon the ability to screen samples against a vast array of probes with the appropriate sensitivity and selectivity. while these factors are significantly influenced by probe design, they are also subject to the particular detection methodology and reagents employed. herein we describe the incorporation of super avidin-biotin system (sabs) and secondary enzymatic enhancement (see) as post-hybridization signal amplification techniques to improve the sensitivity of ol ...201020951861
susceptibility of the common hamster (cricetus cricetus) to francisella tularensis and its effect on the epizootiology of tularemia in an area where both are endemic.francisella tularensis is a highly infectious zoonotic agent causing the disease tularemia. the common hamster (cricetus cricetus) is considered a pest in eastern europe, and believed to be a source of human tularemia infections. we examined the role of the common hamster in the natural cycle of tularemia using serologic methods on 900 hamsters and real-time polymerase chain reaction (pcr) on 100 hamsters in an endemic agricultural area. we collected 374 ixodes acuminatus ticks from the hamsters ...201020966287
molecular immune responses to aerosol challenge with francisella tularensis in mice inoculated with live vaccine candidates of varying efficacy.francisella tularensis is a facultative intracellular bacterial pathogen and the etiological agent of tularemia. the subspecies f. tularensis tularensis is especially virulent for humans when inhaled and respiratory tularemia is associated with high mortality if not promptly treated. a live vaccine strain (lvs) derived from the less virulent holarctica subspecies confers incomplete protection against aerosol challenge with subsp. tularensis. moreover, correlates of protection have not been estab ...201020967278
francisella philomiragia biofilm formation and interaction with the aquatic protist acanthamoeba castellanii.the bacterium francisella philomiragia has been isolated from environmental samples originating from around the globe. f. philomiragia-related strains cause francisellosis of both farmed and wild fish. in addition, occasional human infections caused by f. philomiragia are found in victims of near-drowning and patients with chronic granulomatous disease. we have shown that f. philomiragia forms in vitro biofilms with increased formation at 25 °c over 37 °c conditions. we found that f. philomiragi ...201020972262
tularaemia outbreaks in sakarya, turkey: case-control and environmental studies.tularaemia is an important zoonotic disease that leads to outbreaks. this study aimed to compare the epidemiological characteristics of two tularaemia outbreaks that occurred in the sakarya region of turkey, analyse the risk factors for the development of outbreaks and identify francisella (f.) tularensis in the water samples.201020848064
bronchus-associated lymphoid tissue (balt) and survival in a vaccine mouse model of tularemia.francisella tularensis causes severe pulmonary disease, and nasal vaccination could be the ideal measure to effectively prevent it. nevertheless, the efficacy of this type of vaccine is influenced by the lack of an effective mucosal adjuvant.201020585390
the involvement of il-17a in the murine response to sub-lethal inhalational infection with francisella tularensis.francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. previous reports have underlined the role of cell-mediated immunity and ifngamma in the host response to francisella tularensis infection.201020585449
physiologic reference ranges for captive black-tailed prairie dogs (cynomys ludovicianus).the black-tailed prairie dog (cynomys ludovicianus) is a member of the order rodentia and the family sciuridae. ecologically, prairie dogs are a keystone species in prairie ecology. this species is used as an animal model for human gallbladder disease and diseases caused by infection with clostridium difficile, yersinia pestis, francisella tularensis, and most recently, orthopoxvirus. despite increasing numbers of prairie dogs used in research and kept as pets, few data are available on their ba ...201020587156
the human-bacterial pathogen protein interaction networks of bacillus anthracis, francisella tularensis, and yersinia pestis.bacillus anthracis, francisella tularensis, and yersinia pestis are bacterial pathogens that can cause anthrax, lethal acute pneumonic disease, and bubonic plague, respectively, and are listed as niaid category a priority pathogens for possible use as biological weapons. however, the interactions between human proteins and proteins in these bacteria remain poorly characterized leading to an incomplete understanding of their pathogenesis and mechanisms of immune evasion.201020711500
in vitro and in vivo efficacy of florfenicol for treatment of francisella asiatica infection in tilapia.francisella asiatica is a recently described, gram-negative, facultative intracellular fish pathogen, known to be the causative agent of francisellosis in warm-water fish. francisellosis outbreaks have increased in frequency among commercial aquaculture operations and have caused severe economic losses in every case reported. the lack of effective treatments for piscine francisellosis led us to investigate the potential efficacy of florfenicol for inhibition of f. asiatica in vitro and as an ora ...201020713674
coexistence of pathogens in host-seeking and feeding ticks within a single natural habitat in central germany.the importance of established and emerging tick-borne pathogens in central and northern europe is steadily increasing. in 2007, we collected ixodes ricinus ticks feeding on birds (n = 211) and rodents (n = 273), as well as host-seeking stages (n = 196), in a habitat in central germany. in order to find out more about their natural transmission cycles, the ticks were tested for the presence of lyme disease borreliae, anaplasma phagocytophilum, spotted fever group (sfg) rickettsiae, francisella tu ...201020729315
systems approach to investigating host-pathogen interactions in infections with the biothreat agent francisella. constraints-based model of francisella tularensis.francisella tularensis is a prototypic example of a pathogen for which few experimental datasets exist, but for which copious high-throughout data are becoming available because of its re-emerging significance as biothreat agent. the virulence of francisella tularensis depends on its growth capabilities within a defined environmental niche of the host cell.201020731870
escherichia coli mutants that synthesize dephosphorylated lipid a molecules.the lipid a moiety of escherichia coli lipopolysaccharide is a hexaacylated disaccharide of glucosamine that is phosphorylated at the 1 and 4' positions. expression of the francisella novicida lipid a 1-phosphatase fnlpxe in e. coli results in dephosphorylation of the lipid a proximal unit. coexpression of fnlpxe and the rhizobium leguminosarum lipid a oxidase rllpxq in e. coli converts much of the proximal glucosamine to 2-amino-2-deoxygluconate. expression of the f. novicida lipid a 4'-phospha ...201020795687
the type iv pilin, pila, is required for full virulence of francisella tularensis subspecies tularensis.all four francisella tularensis subspecies possess gene clusters with potential to express type iv pili (tfp). these clusters include putative pilin genes, as well as pilb, pilc and pilq, required for secretion and assembly of tfp. a hallmark of tfp is the ability to retract the pilus upon surface contact, a property mediated by the atpase pilt. interestingly, out of the two major human pathogenic subspecies only the highly virulent type a strains have a functional pilt gene.201020796283
3-deoxy-d-manno-octulosonic acid (kdo) hydrolase identified in francisella tularensis, helicobacter pylori, and legionella pneumophila.3-deoxy-d-manno-octulosonic acid (kdo) is an eight-carbon sugar ubiquitous in gram-negative bacterial lipopolysaccharides (lps). although its biosynthesis is well described, no protein has yet been identified as a kdo hydrolase. however, kdo hydrolase enzymatic activity has been detected in membranes of helicobacter pylori and francisella tularensis and may be responsible for the removal of side-chain kdo from the lps core saccharides. we now report the identification of genes encoding a kdo hyd ...201020801884
transmission dynamics of francisella tularensis subspecies and clades by nymphal dermacentor variabilis (acari: ixodidae).in the united states, the american dog tick, dermacentor variabilis (say) is considered an important biological vector of francisella tularensis, the etiologic agent of tularemia. in this study, we evaluated the vector efficiency of nymphal d. variabilis infected as larvae with differing clades and subspecies (a1b, a2, and type b) of f. tularensis. in all cases, d. variabilis larvae were able to acquire, maintain, and transstadially transmit f. tularensis. significant replication of the bacteria ...201020810833
matrix-assisted laser desorption ionization time-of-flight mass spectrometry: usefulness for taxonomy and epidemiology.matrix-assisted laser desorption ionization time-of-flight (maldi-tof) mass spectrometry (ms) is a powerful tool for the species and subspecies classification of a broad spectrum of bacteria, including gram-positive bacteria such as staphylococcus, streptococcus and listeria, and gram-negative bacteria such as neisseria, salmonella, aeromonas, campylobacter and helicobacter. maldi-tof ms has also been used for the rapid identification and typing of potential bioterrorism agents, including coxiel ...201020825435
phenotypic and genetic characterization of macrolide resistance in francisella tularensis subsp. holarctica biovar i.francisella tularensis subsp. holarctica strains are classified as biovars i and ii, which are susceptible and naturally resistant to the macrolide erythromycin, respectively. the present study was aimed at both selecting biovar i strains with increased levels of erythromycin resistance and characterizing the underlying genetic mechanisms.201020837574
versatile set of orthogonal protecting groups for the preparation of highly branched oligosaccharides.a new set of orthogonal protecting groups has been developed based on the use of a diethylisopropylsilyl (deips), methylnaphthyl (nap), allyl ether, and levulinoyl (lev) ester. the protecting groups are ideally suited for the preparation of highly branched oligosaccharides and their usefulness has been demonstrated by the chemical synthesis of a β-d-man-(1→4)-d-man disaccharide, which is appropriately protected for making a range of part-structures of the unusual core region of the lipopolysacch ...201020845911
characterization of lethal inhalational infection with francisella tularensis in the common marmoset (callithrix jacchus).the intracellular gram-negative pathogen francisella tularensis is the causative agent of tularaemia and is prevalent in many countries in the northern hemisphere. to determine whether the common marmoset (callithrix jacchus) would be a suitable non-human primate model of inhalational tularaemia, a pathophysiology study was undertaken. ten animals were challenged with approximately 10(2) c.f.u. f. tularensis strain schu s4 (f. tularensis subsp. tularensis). to look for trends in the infection, p ...201020558585
francisella tularensis antioxidants harness reactive oxygen species to restrict macrophage signaling and cytokine production.francisella tularensis is the etiologic agent of the highly infectious animal and human disease tularemia. its extreme infectivity and virulence are associated with its ability to evade immune detection, which we now link to its robust reactive oxygen species-scavenging capacity. infection of primary human monocyte-derived macrophages with virulent f. tularensis schus4 prevented proinflammatory cytokine production in the presence or absence of ifn-gamma compared with infection with the attenuate ...201020558723
quantum of infection of francisella tularensis tularensis in host-seeking dermacentor variabilis.the american dog tick, dermacentor variabilis, is fundamental to the perpetuation of francisella tularensis tularensis on martha's vineyard, massachusetts, u.s.a. although infected ticks are relatively common on the island, human cases deriving from tick bite are rare. it may be that the quantum of bacteria within these naturally infected ticks is frequently too small to cause disease. accordingly, we quantified the amount of f.t. tularensis bacteria in host-seeking ticks from the island. contra ...201020563231
accurate detection of low levels of fluorescence emission in autofluorescent background: francisella-infected macrophage cells.cellular autofluorescence, though ubiquitous when imaging cells and tissues, is often assumed to be small in comparison to the signal of interest. uniform estimates of autofluorescence intensity obtained from separate control specimens are commonly employed to correct for autofluorescence. while these may be sufficient for high signal-to-background applications, improvements in detector and probe technologies and introduction of spectral imaging microscopes have increased the sensitivity of fluo ...201020569528
[infection due to francisella tularensis, myocarditis and dilated myocardiopathy]. 201020570415
sdetection of vector-borne agents in lone star ticks, amblyomma americanum (acari: ixodidae), from mississippi.in this study, we evaluated amblyomma americanum (lone star tick) in mississippi for the presence of ehrlichia chaffeensis, causative agent of human monocytic ehrlichiosis; ehrlichia ewingii, causative agent of human and canine granulocytic ehrlichiosis; borrelia lonestari, putative agent of southern tick-associated rash illness; francisella tularensis, the agent of tularemia; and rickettsia spp., particularly r. amblyommii, a suspected pathogen. we collected adult a. americanum from four region ...201020496596
[glandular form of tularemia after arthropod bite--cases report].tularemia is a rare zoonosis. there are a few ways of transmission of f. tularensis known: from the most common: contaminated meat, water, inhalation to rarely considered as insect or tick bite. insect bites are known. the disease may present non specific clinical picture, its course may be acute or chronic. because of polymorphism of clinical picture specific treatment is often delayed. in our paper we present cases of patients, who were diagnosed with tularemia due to horse-fly or tick bite.201020499663
septic pneumonic tularaemia caused by francisella tularensis subsp. holarctica biovar ii.this case of pneumonic tularaemia elucidates two aspects: it is believed to be the first documented case of bacteraemia caused by francisella tularensis subsp. holarctica biovar ii; furthermore, it illustrates the remission of septic pneumonic tularaemia without appropriate anti-infective therapy. a blood culture from a patient with community-acquired pneumonia was found to be positive for f. tularensis subsp. holarctica biovar ii after 10 days of cultivation. meanwhile, the patient had been tre ...201020522628
effective, broad spectrum control of virulent bacterial infections using cationic dna liposome complexes combined with bacterial antigens.protection against virulent pathogens that cause acute, fatal disease is often hampered by development of microbial resistance to traditional chemotherapeutics. further, most successful pathogens possess an array of immune evasion strategies to avoid detection and elimination by the host. development of novel, immunomodulatory prophylaxes that target the host immune system, rather than the invading microbe, could serve as effective alternatives to traditional chemotherapies. here we describe the ...201020523903
francisella tularensis suppresses the proinflammatory response of endothelial cells via the endothelial protein c receptor.various bacterial pathogens activate the endothelium to secrete proinflammatory cytokines and recruit circulating leukocytes. in contrast, there is a distinct lack of activation of these cells by francisella tularensis, the causative agent of tularemia. given the importance of endothelial cells in facilitating innate immunity, we investigated the ability of the attenuated live vaccine strain and virulent schu s4 strain of f. tularensis to inhibit the proinflammatory response of huvecs. living f. ...201020543103
host factors required for modulation of phagosome biogenesis and proliferation of francisella tularensis within the cytosol.francisella tularensis is a highly infectious facultative intracellular bacterium that can be transmitted between mammals by arthropod vectors. similar to many other intracellular bacteria that replicate within the cytosol, such as listeria, shigella, burkholderia, and rickettsia, the virulence of f. tularensis depends on its ability to modulate biogenesis of its phagosome and to escape into the host cell cytosol where it proliferates. recent studies have identified the f. tularensis genes requi ...201020552012
activation of b cell apoptotic pathways in the course of francisella tularensis infection.francisella tularensis is a facultative intracellular, gram-negative bacterium that induces apoptosis in macrophages and b cells. here we show apoptotic pathways that are activated in the ramos human b cell line in the course of f. tularensis infection. live bacteria f. tularensis fsc200 activate caspases 8, 9 and 3, as well as bid; release cytochrome c and apoptosis-inducing factor from mitochondria; and induce depolarization of mitochondrial membrane potential in the ramos cell line, thus lead ...201020600796
characterization of the o-antigen polymerase (wzy) of francisella tularensis.the o-antigen polymerase of gram-negative bacteria has been difficult to characterize. herein we report the biochemical and functional characterization of the protein product (wzy) of the gene annotated as the putative o-antigen polymerase, which is located in the o-antigen biosynthetic locus of francisella tularensis. in silico analysis (homology searching, hydropathy plotting, and codon usage assessment) strongly suggested that wzy is an o-antigen polymerase whose function is to catalyze the a ...201020605777
multiple mechanisms of nadph oxidase inhibition by type a and type b francisella tularensis.ft is a facultative intracellular pathogen that infects many cell types, including neutrophils. in previous work, we demonstrated that the type b ft strain lvs disrupts nadph oxidase activity throughout human neutrophils, but how this is achieved is incompletely defined. here, we used several type a and type b strains to demonstrate that ft-mediated nadph oxidase inhibition is more complex than appreciated previously. we confirm that phagosomes containing ft opsonized with as exclude flavocytoch ...201020610796
method for the isolation of francisella tularensis outer membranes.francisella tularensis is a gram-negative intracellular coccobacillus and the causative agent of the zoonotic disease tularemia. when compared with other bacterial pathogens, the extremely low infectious dose (<10 cfu), rapid disease progression, and high morbidity and mortality rates suggest that the virulent strains of francisella encode for novel virulence factors. surface-exposed molecules, namely outer membrane proteins (omps), have been shown to promote bacterial host cell binding, entry, ...201020613713
biological properties and structure of the lipopolysaccharide of a vaccine strain of francisella tularensis generated by inactivation of a quorum sensing system gene qsec.a knockout mutant with a deletion in a quorum sensing system gene qsec was generated from the vaccine strain francisella tularensis 15 by site-directed mutagenesis. the variant with the inactivated gene qsec differed from the parental strain in growth rate on solid nutrient medium but had the same growth dynamics in liquid nutrient medium. the mutation abolished almost completely the resistance of the vaccine strain to normal rabbit serum and its ability to survive in macrophages; in addition, t ...201020618133
triggering ras signalling by intracellular francisella tularensis through recruitment of pkcα and βi to the sos2/grb2 complex is essential for bacterial proliferation in the cytosol.intracellular proliferation of francisella tularensis is essential for manifestation of the fatal disease tularaemia, and is classified as a category a bioterrorism agent. the f. tularensis-containing phagosome (fcp) matures into a late endosome-like phagosome with limited fusion to lysosomes, followed by rapid bacterial escape into the cytosol. the francisella pathogenicity island (fpi) encodes a type vi-like secretion system, and the fpi-encoded iglc is essential for evasion of lysosomal fusio ...201020618341
construction of a bioluminescence reporter plasmid for francisella tularensis.a francisella tularensis shuttle vector that constitutively expresses the photorhabdus luminescens lux operon in type a and type b strains of f. tularensis was constructed. the bioluminescence reporter plasmid was introduced into the live vaccine strain of f. tularensis and used to follow f. tularensis growth in a murine intranasal challenge model in real-time by bioluminescence imaging. the results show that the new bioluminescence reporter plasmid represents a useful tool for tularemia researc ...201020620161
essential genes from arctic bacteria used to construct stable, temperature-sensitive bacterial vaccines.all bacteria share a set of evolutionarily conserved essential genes that encode products that are required for viability. the great diversity of environments that bacteria inhabit, including environments at extreme temperatures, place adaptive pressure on essential genes. we sought to use this evolutionary diversity of essential genes to engineer bacterial pathogens to be stably temperature-sensitive, and thus useful as live vaccines. we isolated essential genes from bacteria found in the arcti ...201020624965
bioavailability and efficacy of levofloxacin against francisella tularensis in the common marmoset (callithrix jacchus).pharmacokinetic and efficacy studies with levofloxacin were performed in the common marmoset (callithrix jacchus) model of inhalational tularemia. plasma levofloxacin pharmacokinetics were determined in six animals in separate single-dose and multidose studies. plasma drug concentrations were analyzed using liquid chromatography-tandem mass spectrometry-electrospray ionization. on day 7 of a twice-daily dosing regimen of 40 mg/kg, the levofloxacin half-life, maximum concentration, and area under ...201020625157
identification, characterization and immunogenicity of an o-antigen capsular polysaccharide of francisella tularensis.capsular polysaccharides are important factors in bacterial pathogenesis and have been the target of a number of successful vaccines. francisella tularensis has been considered to express a capsular antigen but none has been isolated or characterized. we have developed a monoclonal antibody, 11b7, which recognizes the capsular polysaccharide of f. tularensis migrating on western blot as a diffuse band between 100 kda and 250 kda. the capsule stains poorly on sds-page with silver stain but can be ...201020625403
th17 cytokines in recall responses against francisella tularensis in humans.to determine whether cytokines and t-cell subsets other than th1 cells contribute to secondary immune responses against francisella species, we investigated production of th17-associated cytokines il-17 and il-22 in a recall response to francisella tularensis. peripheral blood mononuclear cells (pbmcs) from volunteers previously immunized with the f. tularensis live vaccine strain (lvs) were stimulated in vitro with bacterial lysates of lvs or a nonpathogenic type a b38 strain. gene expression a ...201020626289
pathology in practice. tularemia. 201020632788
a francisella tularensis live vaccine strain (lvs) mutant with a deletion in capb, encoding a putative capsular biosynthesis protein, is significantly more attenuated than lvs yet induces potent protective immunity in mice against f. tularensis challenge.francisella tularensis, the causative agent of tularemia, is in the top category (category a) of potential agents of bioterrorism. the f. tularensis live vaccine strain (lvs) is the only vaccine currently available to protect against tularemia; however, this unlicensed vaccine is relatively toxic and provides incomplete protection against aerosolized f. tularensis, the most dangerous mode of transmission. hence, a safer and more potent vaccine is needed. as a first step toward addressing this ne ...201020643859
francisella philomiragia septicemia in a dog. 201020649752
deletion of the bacillus anthracis capb homologue in francisella tularensis subspecies tularensis generates an attenuated strain that protects mice against virulent tularaemia.as there is currently no licensed vaccine against francisella tularensis, the causative agent of tularaemia, the bacterium is an agent of concern as a potential bioweapon. although f. tularensis has a low infectious dose and high associated mortality, it possesses few classical virulence factors. an analysis of the f. tularensis subspecies tularensis genome sequence has revealed the presence of a region containing genes with low sequence homology to part of the capbcade operon of bacillus anthra ...201020651039
optimal swab processing recovery method for detection of bioterrorism-related francisella tularensis by real-time pcr.francisella tularensis, the etiological agent of tularemia, is regarded as a potential bioterrorism agent. the advent of bioterrorism has heightened awareness of the need for validated methods for processing environmental samples. in this study we determined the optimal method for processing environmental swabs for the recovery and subsequent detection of f. tularensis by the use of real-time pcr assays. four swab processing recovery methods were compared: heat, sonication, vortexing, and the sw ...201020654658
whole-genome sequencing reveals distinct mutational patterns in closely related laboratory and naturally propagated francisella tularensis strains.the f. tularensis type a strain fsc198 from slovakia and a second strain fsc043, which has attenuated virulence, are both considered to be derivatives of the north american f. tularensis type a strain schu s4. these strains have been propagated under different conditions: the fsc198 has undergone natural propagation in the environment, while the strain fsc043 has been cultivated on artificial media in laboratories. here, we have compared the genome sequences of fsc198, fsc043, and schu s4 to exp ...201020657845
a two-component kdo hydrolase in the inner membrane of francisella novicida.lipid a coats the outer surface of the outer membrane of gram-negative bacteria. in francisella tularensis subspecies novicida lipid a is present either as the covalently attached anchor of lipopolysaccharide (lps) or as free lipid a. the lipid a moiety of francisella lps is linked to the core domain by a single 2-keto-3-deoxy-d-manno-octulosonic acid (kdo) residue. f. novicida kdta is bi-functional, but f. novicida contains a membrane-bound kdo hydrolase that removes the outer kdo unit. the hyd ...201020662782
ulceroglandular tularemia.a 14-year-old boy presented with fevers and nonspecific flulike symptoms, as well as an enlarging ulcerated plaque involving the upper back, lymphadenopathy, and bilateral pulmonary nodules. bacterial cultures of ulcer tissue grew francisella tularensis on enriched chocolate agar plates. making the diagnosis requires a high index of suspicion, and communication with the laboratory to successfully and safely culture these highly pathogenic bacteria is imperative.201020678093
cutting edge: mutation of francisella tularensis mvin leads to increased macrophage absent in melanoma 2 inflammasome activation and a loss of virulence.the mechanisms by which the intracellular pathogen francisella tularensis evades innate immunity are not well defined. we have identified a gene with homology to escherichia coli mvin, a putative lipid ii flippase, which f. tularensis uses to evade activation of innate immune pathways. infection of mice with a f. tularensis mvin mutant resulted in improved survival and decreased bacterial burdens compared to infection with wild-type f. tularensis. the mvin mutant also induced increased absent in ...201020679532
mutations of francisella novicida that alter the mechanism of its phagocytosis by murine macrophages.infection with the bacterial pathogen francisella tularensis tularensis (f. tularensis) causes tularemia, a serious and debilitating disease. francisella tularensis novicida strain u112 (abbreviated f. novicida), which is closely related to f. tularensis, is pathogenic for mice but not for man, making it an ideal model system for tularemia. intracellular pathogens like francisella inhibit the innate immune response, thereby avoiding immune recognition and death of the infected cell. because acti ...201020686600
long lived protection against pneumonic tularemia is correlated with cellular immunity in peripheral, not pulmonary, organs.protection against the intracellular bacterium francisella tularensis within weeks of vaccination is thought to involve both cellular and humoral immune responses. however, the relative roles for cellular and humoral immunity in long lived protection against virulent f. tularensis are not well established. here, we dissected the correlates of immunity to pulmonary infection with virulent f. tularensis strain schus4 in mice challenged 30 and 90 days after subcutaneous vaccination with lvs. regard ...201020688042
objections to the transfer of francisella novicida to the subspecies rank of francisella tularensis. 201020688748
objections to the transfer of francisella novicida to the subspecies rank of francisella tularensis - response to johansson et al. 201020688749
deep mitochondrial dna lineage divergences within alberta populations of dermacentor albipictus (acari: ixodidae) do not indicate distinct species.the winter tick dermacentor albipictus (packard) has a single-host life cycle that allows it to reach severe infestation levels on ungulates, particularly moose. genotypic variation within these and related ticks has been a source of taxonomic confusion, although the continuity in their morphology and life history has generally been interpreted as indicating the existence of a single species. to further investigate this variation, we sequenced regions of two mitochondrial dna (mtdna) genes (coi ...201020695271
detection of francisella tularensis in alaskan mosquitoes (diptera: culicidae) and assessment of a laboratory model for transmission.tularemia is a zoonotic disease caused by the category a bioterrorism agent francisella tularensis. in scandinavia, tularemia transmission by mosquitoes has been widely cited in the literature. we tested >2,500 mosquitoes captured in alaska and found francisella dna in 30% of pooled samples. to examine the potential for transmission of francisella by mosquitoes, we developed a mosquito model of francisella infection. larvae of anopheles gambiae giles and aedes aegypti (l.) readily ingest f. tula ...201020695280
the fsle homolog, ftl_0439 (fupa/b), mediates siderophore-dependent iron uptake in francisella tularensis lvs.the gram-negative pathogen francisella tularensis secretes a siderophore to obtain essential iron by a tonb-independent mechanism. the fslabcde locus, encoding siderophore-related functions, is conserved among different francisella strains. in the virulent strain schu s4, fsle is essential for siderophore utilization and for growth under conditions of iron limitation. in contrast, we found that deletion of fsle did not affect siderophore utilization by the attenuated live vaccine strain (lvs). w ...201020696823
large direct repeats flank genomic rearrangements between a new clinical isolate of francisella tularensis subsp. tularensis a1 and schu s4.francisella tularensis subspecies tularensis consists of two separate populations a1 and a2. this report describes the complete genome sequence of ne061598, an f. tularensis subspecies tularensis a1 isolated in 1998 from a human with clinical disease in nebraska, united states of america. the genome sequence was compared to schu s4, an f. tularensis subspecies tularensis a1a strain originally isolated in ohio in 1941. it was determined that there were 25 nucleotide polymorphisms (22 snps and 3 i ...201020140244
interaction of francisella asiatica with tilapia (oreochromis niloticus) innate immunity.members of the genus francisella are facultative intracellular bacteria that cause important diseases in a wide variety of animals worldwide, including humans and fish. several genes that are important for intramacrophage survival have been identified, including the iglc gene, which is found in the iglabcd operon in the francisella sp. pathogenicity island (fpi). in the present study, we examined the interaction of wild-type francisella asiatica and a delta iglc mutant strain with fish serum and ...201020160018
tularaemia in minnesota: case report and brief epidemiology.the 2008 case presented here of tularaemia in a cat and its owner occurred in an urban setting and was associated with animal contact, a relatively rare mode of transmission in minnesota in recent years. response to this case exemplified a 'one health' approach involving pre-existing relationships, cooperation between multiple disciplines and laboratory infrastructure that facilitated information sharing.201020163576
subolesin expression in response to pathogen infection in ticks.ticks (acari: ixodidae) are vectors of pathogens worldwide that cause diseases in humans and animals. ticks and pathogens have co-evolved molecular mechanisms that contribute to their mutual development and survival. subolesin was discovered as a tick protective antigen and was subsequently shown to be similar in structure and function to akirins, an evolutionarily conserved group of proteins in insects and vertebrates that controls nf-kb-dependent and independent expression of innate immune res ...201020170494
detoxified endotoxin vaccine (j5dlps/omp) protects mice against lethal respiratory challenge with francisella tularensis schus4.francisella tularensis is a category a select agent. j5dlps/omp is a novel vaccine construct consisting of detoxified, o-polysaccharide side chain-deficient, lipopolysaccharide non-covalently complexed with the outer membrane protein of n. meningitidis group b. immunization elicits high-titer polyclonal antibodies specific for the highly-conserved epitopes expressed within the glycolipid core that constitutes gram-negative bacteria (e.g., f. tularensis). mice immunized intranasally with j5dlps/o ...201020170768
tularemia pneumonia.francisella tularensis is a zoonotic infection that can be acquired in multiple ways, including a bite from an arthropod, the handling of animal carcasses, consumption of contaminated food and water, or inhalation of infected particles. the most virulent subspecies of f tularensis is type a, which is almost exclusively seen in north america. pneumonia can occur in tularemia, as either a primary process from direct inhalation, or as a secondary manifestation of ulceroglandular or typhoidal diseas ...201020171544
multimethodological approach to identification of glycoproteins from the proteome of francisella tularensis, an intracellular microorganism.it appears that most glycoproteins found in pathogenic bacteria are associated with virulence. despite the recent identification of novel virulence factors, the mechanisms of virulence in francisella tularensis are poorly understood. in spite of its importance, questions about glycosylation of proteins in this bacterium and its potential connection with bacterial virulence have not been answered yet. in the present study, several putative francisella tularensis glycoproteins were characterized t ...201020175567
type i ifn signaling constrains il-17a/f secretion by gammadelta t cells during bacterial infections.recognition of intracellular bacteria by macrophages leads to secretion of type i ifns. however, the role of type i ifn during bacterial infection is still poorly understood. francisella tularensis, the causative agent of tularemia, is a pathogenic bacterium that replicates in the cytosol of macrophages leading to secretion of type i ifn. in this study, we investigated the role of type i ifns in a mouse model of tularemia. mice deficient for type i ifn receptor (ifnar1(-/-)) are more resistant t ...201020176744
cpg oligodeoxyribonucleotides protect mice from burkholderia pseudomallei but not francisella tularensis schu s4 aerosols.abstract: studies have shown that cpg oligodeoxyribonucleotides (odn) protect mice from various bacterial pathogens, including burkholderia pseudomallei and francisella tularensis live vaccine strain (lvs), when administered before parenteral challenge. given the potential to develop cpg odn as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from cpg odn-treated c57bl/6 mice to determine whether previously-reported protect ...201020181102
identification of francisella tularensis by whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry: fast, reliable, robust, and cost-effective differentiation on species and subspecies levels.francisella tularensis, the causative agent of tularemia, is a potential agent of bioterrorism. the phenotypic discrimination of closely related, but differently virulent, francisella tularensis subspecies with phenotyping methods is difficult and time-consuming, often producing ambiguous results. as a fast and simple alternative, matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) was applied to 50 different strains of the genus francisella to assess its ...201020181907
Refresh
firstprev
12345678910...
nextlast
Displaying items 201 - 300 of 2254