Publications

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laboratory-acquired infections.laboratory-acquired infections due to a wide variety of bacteria, viruses, fungi, and parasites have been described. although the precise risk of infection after an exposure remains poorly defined, surveys of laboratory-acquired infections suggest that brucella species, shigella species, salmonella species, mycobacterium tuberculosis, and neisseria meningitidis are the most common causes. infections due to the bloodborne pathogens (hepatitis b virus, hepatitis c virus, and human immunodeficiency ...200919480580
differential susceptibility of sprague-dawley and fischer 344 rats to infection by francisella tularensis.the type a and b subspecies of francisella tularensis cause severe disease, tularemia, in humans. however, only the former can be lethal especially if inhaled. it is likely that non-lethal infection is due at least in part to the ability of innate host defenses to control pathogen growth whilst acquired immunity develops. most common small laboratory animals rapidly succumb to clinical strains of f. tularensis and are, therefore, poor models with which to study innate immunity. in an attempt to ...200919490832
mucosal immunotherapy for protection from pneumonic infection with francisella tularensis.previous studies have demonstrated that systemically administered immunotherapy can protect mice from systemic challenge with the bacterial pathogen francisella tularensis. however, for protection from inhalational challenge with this bacterium, we wondered if mucosally administered immunotherapy might be more effective. therefore, we administered cationic liposome-dna complexes (cldc), which are potent activators of innate immunity, intranasally (i.n.) and assessed the effectiveness of protecti ...200919490961
pyrin critical to macrophage il-1beta response to francisella challenge.relative to monocytes, human macrophages are deficient in their ability to process and release il-1beta. in an effort to explain this difference, we used a model of il-1beta processing and release that is dependent upon bacterial escape into the cytosol. fresh human blood monocytes were compared with monocyte-derived macrophages (mdm) for their il-1beta release in response to challenge with francisella novicida. although both cell types produced similar levels of il-1beta mrna and intracellular ...200919494323
transovarial transmission of francisella-like endosymbionts and anaplasma phagocytophilum variants in dermacentor albipictus (acari: ixodidae).dermacentor albipictus (packard) is a north american tick that feeds on cervids and livestock. it is a suspected vector of anaplasmosis in cattle, but its microbial flora and vector potential remain underevaluated. we screened d. albipictus ticks collected from minnesota white-tailed deer (odocoileus virginianus) for bacteria of the genera anaplasma, ehrlichia, francisella, and rickettsia using polymerase chain reaction (pcr) gene amplification and sequence analyses. we detected anaplasma phagoc ...200919496436
contribution of citrulline ureidase to francisella tularensis strain schu s4 pathogenesis.the citrulline ureidase (ctu) activity has been shown to be associated with highly virulent francisella tularensis strains, including schu s4, while it is absent in avirulent or less virulent strains. a definitive role of the ctu gene in virulence and pathogenesis of f. tularensis schu s4 has not been assessed; thus, an understanding of the significance of this phenotype is long overdue. ctu is a carbon-nitrogen hydrolase encoded by the citrulline ureidase (ctu) gene (ftt0435) on the f. tularens ...200919502406
reintroduction of two deleted virulence loci restores full virulence to the live vaccine strain of francisella tularensis.a disadvantage of several old vaccines is that the genetic events resulting in the attenuation are often largely unknown and reversion to virulence cannot be excluded. in the 1950s, a live vaccine strain, lvs, was developed from a type b strain of francisella tularensis, the causative agent of tularemia. lvs, which is highly attenuated for humans but still virulent for mice by some infection routes, has been extensively studied and found to protect staff from laboratory-acquired tularemia. the e ...200919506014
francisella sp., an emerging pathogen of tilapia, oreochromis niloticus (l.), in costa rica.francisella sp. is an emergent bacterial pathogen that causes acute to chronic disease in warm and cold water cultured and wild fish species. during the past 3 years, the bacterium has been detected in tilapia, oreochromis niloticus, cultured in costa rica. infected fish presented non-specific clinical signs, such as erratic swimming, anorexia, anaemia, exophthalmia and high mortality. upon macroscopic and microscopic examination, several internal organs (mainly spleen and kidney) were enlarged ...200919515205
vaccination of fischer 344 rats against pulmonary infections by francisella tularensis type a strains.pneumonic tularemia caused by inhalation of the type a strains of francisella tularensis is associated with high morbidity and mortality in humans. the only vaccine known to protect humans against this disease is the attenuated live vaccine strain (lvs), but it is not currently registered for human use. to develop a new generation of vaccines, multiple animal models are needed that reproduce the human response to f. tularensis infection and vaccination. we examined the potential use of fischer 3 ...200919520198
molecular evolutionary consequences of niche restriction in francisella tularensis, a facultative intracellular pathogen.francisella tularensis is a potent mammalian pathogen well adapted to intracellular habitats, whereas f. novicida and f. philomiragia are less virulent in mammals and appear to have less specialized lifecycles. we explored adaptations within the genus that may be linked to increased host association, as follows. first, we determined the genome sequence of f. tularensis subsp. mediasiatica, the only subspecies that had not been previously sequenced. this genome, and those of 12 other f. tularensi ...200919521508
environmental adaptation of francisella tularensis.concerns over weaponizable bacteria have recently prompted considerable interest in francisella tularensis (ft). in addition to its potential illicit use, ft occurs naturally in diverse ecological niches including mammals, arthropods, and fresh water protozoans. here we review the current knowledge of ft adaptation which has ramifications for both basic and applied research.200919524059
analyzing time-dependent microarray data using independent component analysis derived expression modes from human macrophages infected with f. tularensis holartica.the analysis of large-scale gene expression profiles is still a demanding and extensive task. modern machine learning and data mining techniques developed in linear algebra, like independent component analysis (ica), become increasingly popular as appropriate tools for analyzing microarray data. we applied ica to analyze kinetic gene expression profiles of human monocyte derived macrophages (mdm) from three different donors infected with francisella tularensis holartica and compared them to more ...200919535009
rationally designed tularemia vaccines.tularemia, caused by the gram-negative bacterium francisella tularensis, can be contracted by the bite of an arthropod vector or by inhalation. this disease occurs relatively infrequently but can be severe and even life-threatening if untreated. until recently, there were few laboratories studying this organism; however, concerns over its potential use as a biological weapon have led to renewed attention to f. tularensis research, particularly in the area of vaccine development. advances in the ...200919538114
editorial: proinflammatory cytokines in pneumonic tularemia: too much too late? 200919720615
substituted diphenyl ethers as a broad-spectrum platform for the development of chemotherapeutics for the treatment of tularaemia.the national institute of allergy and infectious disease classifies francisella tularensis as a category a priority pathogen. despite the availability of drugs for treating tularaemia, the mortality in naturally acquired cases can still approach 30%. in addition, the usefulness of existing drugs for treatment in response to exposure or for prophylaxis is limited because of toxicity and delivery concerns. the aim of this study was to assess the efficacy of the lead alkyl-substituted diphenyl ethe ...200919734171
innate immune response during yersinia infection: critical modulation of cell death mechanisms through phagocyte activation.yersinia pestis, the etiological agent of plague, is one of the most deadly pathogens on our planet. this organism shares important attributes with its ancestral progenitor, yersinia pseudotuberculosis, including a 70-kb virulence plasmid, lymphotropism during growth in the mammalian host, and killing of host macrophages. infections with both organisms are biphasic, where bacterial replication occurs initially with little inflammation, followed by phagocyte influx, inflammatory cytokine producti ...200919734471
global transcriptional response to spermine, a component of the intramacrophage environment, reveals regulation of francisella gene expression through insertion sequence elements.tularemia is caused by the category a biodefense agent francisella tularensis. this bacterium is associated with diverse environments and a plethora of arthropod and mammalian hosts. how f. tularensis adapts to these different conditions, particularly the eukaryotic intracellular environment in which it replicates, is poorly understood. here, we demonstrate that the polyamines spermine and spermidine are environmental signals that alter bacterial stimulation of host cells. genomewide analysis sh ...200919749055
a novel role for plasmin-mediated degradation of opsonizing antibody in the evasion of host immunity by virulent, but not attenuated, francisella tularensis.opsonization by abs represents a critical component of the host immune response against many pathogens. the mechanisms by which virulent microbes evade this protective response are not completely understood. in disease mediated by francisella tularensis, ab can effectively protect against infections with attenuated strains, for example, lvs, but not virulent strains such as schus4. thus, it is likely that schus4 has mechanisms, which are not present in lvs, that allow evasion of opsonization by ...200919752236
complete genome sequence of francisella tularensis subspecies holarctica ftnf002-00.francisella tularensis subspecies holarctica ftnf002-00 strain was originally obtained from the first known clinical case of bacteremic f. tularensis pneumonia in southern europe isolated from an immunocompetent individual. the ftnf002-00 complete genome contains the rd(23) deletion and represents a type strain for a clonal population from the first epidemic tularemia outbreak in spain between 1997-1998. here, we present the complete sequence analysis of the ftnf002-00 genome. the complete genom ...200919756146
differentiation of gram-negative bacterial aerosol exposure using detected markers in bronchial-alveolar lavage fluid.the identification of biosignatures of aerosol exposure to pathogens has the potential to provide useful diagnostic information. in particular, markers of exposure to different types of respiratory pathogens may yield diverse sets of markers that can be used to differentiate exposure. we examine a mouse model of aerosol exposure to known gram negative bacterial pathogens, francisella tularensis novicida and pseudomonas aeruginosa. mice were subjected to either a pathogen or control exposure and ...200919756149
rela regulates virulence and intracellular survival of francisella novicida.analysis of the genome of francisella tularensis has revealed few regulatory systems, and how the organism adapts to conditions in different niches is poorly understood. the stringent response is a global stress response mediated by (p)ppgpp. the enzyme rela has been shown to be involved in generation of this signal molecule in a range of bacterial species. we investigated the effect of inactivation of the rela gene in francisella by generating a mutant in francisella novicida. under amino acid ...200919762448
francisella tularensis novicida proteomic and transcriptomic data integration and annotation based on semantic web technologies.this paper summarises the lessons and experiences gained from a case study of the application of semantic web technologies to the integration of data from the bacterial species francisella tularensis novicida (fn). fn data sources are disparate and heterogeneous, as multiple laboratories across the world, using multiple technologies, perform experiments to understand the mechanism of virulence. it is hard to integrate these data sources in a flexible manner that allows new experimental data to b ...200919796400
proteome analysis of an attenuated francisella tularensis dsba mutant: identification of potential dsba substrate proteins.francisella tularensis (f. tularensis) is highly infectious for humans via aerosol route and untreated infections with the highly virulent subsp. tularensis can be fatal. our knowledge regarding key virulence determinants has increased recently but is still somewhat limited. surface proteins are potential virulence factors and therapeutic targets, and in this study, we decided to target three genes encoding putative membrane lipoproteins in f. tularensis lvs. one of the genes encoded a protein w ...200919799467
generation of heterogeneous memory t cells by live attenuated tularemia vaccine in humans.there is very limited evidence concerning the phenotype, function, and homing characteristics of memory t (t(m)) cells elicited by vaccination against intracellular bacteria in humans. here we studied t(m) subsets elicited by exposure to francisella tularensis in humans as a model of immunity to intracellular bacteria. to this end, t(m) cells were evaluated in two groups: (1) subjects immunized with live attenuated tularemia vaccine by skin scarification and (2) tularemia naturally infected subj ...200919799845
[severe tularaemia mimicking glandular tuberculosis during adalimumab therapy].tularaemia is an anthropozoonosis, transmitted by small mammals (hares) and arthropods (ticks, horseflies). the causative agent is francisella tularensis, a facultatively intracellular gram-negative bacillus. we report a case of tularaemia in its ulceroglandular form occurring during methotrexate and adalimumab treatment (humira) for rheumatoid arthritis.200919801257
programmed cell death and the pathogenesis of tissue injury induced by type a francisella tularensis.francisella tularensis is a highly virulent bacterial species that causes various forms of tularemia in humans. the urgency in understanding the pathogenesis of these diseases has stimulated unprecedented interest in this bacterial species over the past few years. recent findings underscore a number of important distinctions between the francisella ssp. and emphasize the importance of using type a f. tularensis strains when characterizing pathophysiological responses that are relevant to the let ...200919811540
whole genome single nucleotide polymorphism based phylogeny of francisella tularensis and its application to the development of a strain typing assay.a low genetic diversity in francisella tularensis has been documented. current dna based genotyping methods for typing f. tularensis offer a limited and varying degree of subspecies, clade and strain level discrimination power. whole genome sequencing is the most accurate and reliable method to identify, type and determine phylogenetic relationships among strains of a species. however, lower cost typing schemes are necessary in order to enable typing of hundreds or even thousands of isolates.200919811647
[a patient with a fever and an eschar caused by tularemia].a 38-year-old man presented at the first-aid department complaining of fever, general malaise and a painful left groin. the complaints had started shortly after an active holiday in finland. physical examination showed enlarged left sided inguinal lymph nodes and a marked eschar on the left lower leg. in terms of differential diagnosis a rickettsia or a tularemia infection were considered. the pathogen for tularemia, francisella tularensis subspecies holarctica, was isolated in wound discharge f ...200919818182
francisella tularensis type a strains cause the rapid encystment of acanthamoeba castellanii and survive in amoebal cysts for three weeks postinfection.francisella tularensis, the causative agent of the zoonotic disease tularemia, has recently gained increased attention due to the emergence of tularemia in geographical areas where the disease has been previously unknown and to the organism's potential as a bioterrorism agent. although f. tularensis has an extremely broad host range, the bacterial reservoir in nature has not been conclusively identified. in this study, the ability of virulent f. tularensis strains to survive and replicate in the ...200919820161
humans and evolutionary and ecological forces shaped the phylogeography of recently emerged diseases.the development of human civilizations and global commerce has led to the emergence and worldwide circulation of many infectious diseases. anthrax, plague and tularaemia are three zoonotic diseases that have been intensely studied through genome characterization of the causative species and phylogeographical analyses. a few highly fit genotypes in each species represent the causative agents for most of the observed disease cases. together, mutational and selective forces create highly adapted pa ...200919820723
environmental and intracellular regulation of francisella tularensis ripa.francisella tularensis is a highly virulent, facultative intracellular pathogen and the etiologic agent of the zoonotic disease tularemia. ripa is a cytoplasmic membrane protein that is conserved among francisella species and is required for intracellular growth. f. tularensis ripa deletion mutants escape the phagosome of infected cells, but unlike wild type organisms fail to replicate in the host cell cytoplasm.200919821974
water-borne outbreak of oropharyngeal and glandular tularemia in georgia: investigation and follow-up.in november 2006, an outbreak of waterborne tularemia occurred in an eastern region in the republic of georgia. outbreak investigation revealed 26 cases: 21 oropharyngeal and 5 glandular tularemia cases.200919826763
bacillus anthracis, francisella tularensis and yersinia pestis. the most important bacterial warfare agents - review.there are three most important bacterial causative agents of serious infections that could be misused for warfare purposes: bacillus anthracis (the causative agent of anthrax) is the most frequently mentioned one; however, fracisella tularensis (causing tularemia) and yersinia pestis (the causative agent of plague) are further bacterial agents enlisted by centers for disease control and prevention into the category a of potential biological weapons. this review intends to summarize basic informa ...200919826916
[the time course of changes in cell immunological parameters during administration of live dry plague vaccine].the study of the time course of changes in cell immunological parameters by a magnetic separation technique in human beings during the administration of plague vaccine in relation to the immunological load revealed the higher blood levels of all t lymphocyte subpopulations on day 14 after vaccination. these changes are most typical of a primary vaccinated cohort. the increased frequency of plague vaccine administration and multiple immunizations with live plague, anthrax, and tularemia vaccines ...200919827193
[identification and characterization of the francisella sp. strain 08hl01032 isolated in air condition systems].to identify and characterize the strain 08h101032 was isolated from air condition systems in the routine investigations of legionella in guangzhou, china, in 2008.200919835160
effect of dehydrated storage on the survival of francisella tularensis in infant formula.francisella tularensis is a gram-negative bacterium that can cause gastrointestinal or oropharyngeal tularemia in humans from ingestion of contaminated food or water. despite the potential for accidental or intentional contamination of foods with f. tularensis, there are few studies on the long-term survivability of this organism in food matrices. infant formula has previously been implicated as a vehicle for the transmission of a variety of bacterial pathogens in infants. in this study, we inve ...200919835784
crystal structures of the histidine acid phosphatase from francisella tularensis provide insight into substrate recognition.histidine acid phosphatases catalyze the transfer of a phosphoryl group from phosphomonoesters to water at acidic ph using an active-site histidine. the histidine acid phosphatase from the category a pathogen francisella tularensis (fthap) has been implicated in intramacrophage survival and virulence, motivating interest in understanding the structure and mechanism of this enzyme. here, we report a structure-based study of ligand recognition by fthap. the 1.70-a-resolution structure of fthap com ...200919836403
francisella tularensis vaccines.francisella tularensis has attracted attention historically as a biological weapon, due to its high infectivity in aerosols, and the severity of disease in humans. there is no licensed vaccine currently available, although an attenuated live vaccine strain (lvs) was identified in the middle of the last century and has been successfully used to protect humans. efforts are underway to determine the basis of attenuation of lvs, and to understand the immunity required for protection. alternative app ...200919837286
francisella asiatica sp. nov. isolated from farmed tilapia (oreochromis sp.) and elevation of francisella philomiragia subsp. noatunensis to species rank as francisella noatunensis comb. nov., sp. nov.bacterial isolates from diseased farmed tilapia (oreochromis sp.) from costa rica (pq 1104), atlantic salmon (salmo salar) from chile (pq 1106) and three-line grunt (parapristipoma trilineatum) from japan (ehime-1) were characterized by phenotypic and molecular taxonomic methods. these isolates were gram-negative, oxidase negative, non-motile, strictly aerobic cocco-bacilli, produced h2s from cysteine supplemented media, which is phenotypically consistent with the genus francisella. comparison o ...200919783606
interleukin-17 is required for t helper 1 cell immunity and host resistance to the intracellular pathogen francisella tularensis.the importance of t helper type 1 (th1) cell immunity in host resistance to the intracellular bacterium francisella tularensis is well established. however, the relative roles of interleukin (il)-12-th1 and il-23-th17 cell responses in immunity to f. tularensis have not been studied. the il-23-th17 cell pathway is critical for protective immunity against extracellular bacterial infections. in contrast, the il-23-th17 cell pathway is dispensable for protection against intracellular pathogens such ...200919853481
possible interaction between a rodenticide treatment and a pathogen in common vole (microtus arvalis) during a population peak.a common vole (microtus arvalis) population peak in northern spain in 2007 was treated with large scale application of chlorophacinone, an anticoagulant rodenticide of the indandione family. voles found dead and trapped alive were collected in treated and untreated areas. residues of chlorophacinone were analyzed in liver of voles by hplc-uv. also, the presence of the pathogen francisella tularensis was analyzed by pcr in samples of vole spleen. chlorophacinone (82-3800 ng/g; wet weight liver) w ...200919863999
small molecule control of virulence gene expression in francisella tularensis.in francisella tularensis, the sspa protein family members mgla and sspa form a complex that associates with rna polymerase (rnap) to positively control the expression of virulence genes critical for the intramacrophage growth and survival of the organism. although the association of the mgla-sspa complex with rnap is evidently central to its role in controlling gene expression, the molecular details of how mgla and sspa exert their effects are not known. here we show that in the live vaccine st ...200919876386
francisella virulence: significant advances, ongoing challenges and unmet needs.francisella tularensis, the causative agent of tularemia, is an organism of concern as a potential biowarfare agent. progress towards understanding the molecular basis of pathogenicity has been hampered by a lack of tools with which to manipulate the pathogen. however, the availability of genome sequence data for a range of strains and the development of a range of plasmids and mutagenesis protocols for use in francisella has resulted in a huge advance in understanding. no licensed vaccine is ye ...200919863250
francisella tularensis subsp. novicida isolated from a human in arizona.francisella tularensis is the etiologic agent of tularemia and is classified as a select agent by the centers for disease control and prevention. currently four known subspecies of f. tularensis that differ in virulence and geographical distribution are recognized:tularensis (type a), holarctica (type b), mediasiatica, and novicida. because of the select agent status and differences in virulence and geographical location, the molecular analysis of any clinical case of tularemia is of particular ...200919895698
interleukin-17 kick-starts t helper 1 cell differentiation.in this issue of immunity, lin et al. (2009) implicate interleukin-17 in the regulation of t helper 1 (th1) cell immunity against francisella tularensis. these findings add a unique twist to the cytokine regulation of t cell differentiation and function.200919932069
tlr-dependent control of francisella tularensis infection and host inflammatory responses.francisella tularensis is the causative agent of tularemia and is classified as a category a select agent. recent studies have implicated tlr2 as a critical element in the host protective response to f. tularensis infection, but questions remain about whether tlr2 signaling dominates the response in all circumstances and with all species of francisella and whether f. tularensis pamps are predominantly recognized by tlr2/tlr1 or tlr2/tlr6. to address these questions, we have explored the role of ...200919936231
akt and ship modulate francisella escape from the phagosome and induction of the fas-mediated death pathway.francisella tularensis infects macrophages and escapes phago-lysosomal fusion to replicate within the host cytosol, resulting in host cell apoptosis. here we show that the fas-mediated death pathway is activated in infected cells and correlates with escape of the bacterium from the phagosome and the bacterial burden. our studies also demonstrate that constitutive activation of akt, or deletion of ship, promotes phago-lysosomal fusion and limits bacterial burden in the host cytosol, and the subse ...200919936232
working toward the future: insights into francisella tularensis pathogenesis and vaccine development.francisella tularensis is a facultative intracellular gram-negative pathogen and the etiological agent of the zoonotic disease tularemia. recent advances in the field of francisella genetics have led to a rapid increase in both the generation and subsequent characterization of mutant strains exhibiting altered growth and/or virulence characteristics within various model systems of infection. in this review, we summarize the major properties of several francisella species, including f. tularensis ...200919946137
tick-borne agents in rodents, china, 2004-2006.a total of 705 rodents from 6 provinces and autonomous regions of mainland people's republic of china were tested by pcrs for tick-borne agents (anaplasma phagocytophilum, borrelia burgdorferi sensu lato, spotted fever group rickettsiae, and francisella tularensis). infection rates were 5.5%, 6.7%, 9.1% and 5.0%, respectively. eighteen (2.6%) rodents of 10 species were positive for 2 or 3 agents. sequence analysis of pcr products confirmed the presence and genotypes of detected agents. these fin ...200919961668
landscape epidemiology of tularemia outbreaks in sweden.summer outbreaks of tularemia that occurred from 1995 through 2005 in 2 locations in sweden affected 441 persons. we performed an epidemiologic investigation of these outbreaks using a novel strategy, involving high-resolution genotyping of francisella tularensis isolates obtained from 136 patients (using 18 genetic markers developed from 6 f. tularensis genome sequences) and interviews with the patients. strong spatial associations were found between f. tularensis subpopulations and the places ...200919961673
identification of francisella tularensis cluster in central and western europe.we conducted a molecular analysis of francisella tularensis strains isolated in switzerland and identified a specific subpopulation belonging to a cluster of f. tularensis subsp. holarctica that is widely dispersed in central and western continental europe. this subpopulation was present before the tularemia epidemics on the iberian peninsula.200919961699
[pandora's box: pathogens in ixodes ricinus ticks in central europe].among the various species of hard ticks, ixodes ricinus is the most frequently found tick throughout europe. as with other ixodid ticks, the developmental cycle runs through three stages. in each stage a blood meal is required in order to develop to the next stage. ixodes ricinus has been found to feed on more than 300 different vertebrate species. usually, larval ticks feed on small mammals such as mice and become infected with various microorganisms and viruses, of which some are substantial p ...200919998007
eradication of intracellular francisella tularensis in thp-1 human macrophages with a novel autophagy inducing agent.autophagy has been shown recently to play an important role in the intracellular survival of several pathogenic bacteria. in this study, we investigated the effect of a novel small-molecule autophagy-inducing agent, ar-12, on the survival of francisella tularensis, the causative bacterium of tularemia in humans and a potential bioterrorism agent, in macrophages.200920003180
kinetic characterization and phosphoregulation of the francisella tularensis 1-deoxy-d-xylulose 5-phosphate reductoisomerase (mep synthase).deliberate and natural outbreaks of infectious disease underscore the necessity of effective vaccines and antimicrobial/antiviral therapeutics. the prevalence of antibiotic resistant strains and the ease by which antibiotic resistant bacteria can be intentionally engineered further highlights the need for continued development of novel antibiotics against new bacterial targets. isoprenes are a class of molecules fundamentally involved in a variety of crucial biological functions. mammalian cells ...200920011597
assessment of low-molecular-weight antioxidants in francisella tularensis infected hosts: comparison of two rodents with different susceptibility to tularemia.bacterium francisella tularensis is the causative agent of tularemia disease. it is a zoonosis accompanied with high mortality when untreated. small rodents and hares, in particular, are natural reservoirs of tularemia. despite physiological similarity of common hosts, tularemia exerts different mortality rates. the pathogenesis of tularemia is still not fully understood. the main pathway is associated with proliferation in macrophages after activation by reactive oxygen species in phagosomes.200920027169
genome sequence of the endosymbiont rickettsia peacockii and comparison with virulent rickettsia rickettsii: identification of virulence factors.rickettsia peacockii, also known as the east side agent, is a non-pathogenic obligate intracellular bacterium found as an endosymbiont in dermacentor andersoni ticks in the western usa and canada. its presence in ticks is correlated with reduced prevalence of rickettsia rickettsii, the agent of rocky mountain spotted fever. it has been proposed that a virulent sfg rickettsia underwent changes to become the east side agent. we determined the genome sequence of r. peacockii and provide a compariso ...200920027221
a real-time pcr array for hierarchical identification of francisella isolates.a robust, rapid and flexible real-time pcr assay for hierarchical genetic typing of clinical and environmental isolates of francisella is presented. typing markers were found by multiple genome and gene comparisons, from which 23 canonical single nucleotide polymorphisms (cansnps) and 11 canonical insertion-deletion mutations (canindels) were selected to provide phylogenetic guidelines for classification from genus to isolate level. the specificity of the developed assay, which uses 68 wells of ...200920027310
the effect of interferon-gamma and lipopolysaccharide on the growth of francisella tularensis lvs in murine macrophage-like cell line j774.francisella tularensis, a causative agent of human tularemia, displaying the ability to proliferate inside the human cells.200920073421
simultaneous detection of cdc category "a" dna and rna bioterrorism agents by use of multiplex pcr & rt-pcr enzyme hybridization assays.assays to simultaneously detect multiple potential agents of bioterrorism are limited. two multiplex pcr and rt-pcr enzyme hybridization assays (mpcr-eha, mrt-pcr-eha) were developed to simultaneously detect many of the cdc category "a" bioterrorism agents. the "bio t" dna assay was developed to detect: variola major (vm), bacillus anthracis (ba), yersinia pestis (yp), francisella tularensis (ft) and varicella zoster virus (vzv). the "bio t" rna assay (mrt-pcr-eha) was developed to detect: ebola ...200920224751
[development of a universal primers pcr-coupled liquid bead array to detect biothreat bacteria].to develop a fast, high-throughput screening method with suspension array technique for simultaneous detection of biothreat bacteria.200920137470
mir-155 induction by f. novicida but not the virulent f. tularensis results in ship down-regulation and enhanced pro-inflammatory cytokine response.the intracellular gram-negative bacterium francisella tularensis causes the disease tularemia and is known for its ability to subvert host immune responses. previous work from our laboratory identified the pi3k/akt pathway and ship as critical modulators of host resistance to francisella. here, we show that ship expression is strongly down-regulated in monocytes and macrophages following infection with f. tularensis novicida (f.n.). to account for this negative regulation we explored the possibi ...200920041145
attenuation of the fish pathogen francisella sp. by mutation of the iglc* gene.fish francisellosis is an emergent disease caused by gram-negative facultative intracellular bacteria of the genus francisella. different strains of the bacterium have caused high mortalities in warmwater and coldwater fish species. francisella sp. isolates from fish have been found to share more than 97% identity to the human pathogen francisella tularensis upon 16s ribosomal rna sequence comparison. homologue genes of the f. tularensis intracellular growth locus (igla*, iglb*, iglc*, and igld* ...200920043398
pathological and microbiological studies of japanese hare (lepus brachyurus angustidens) naturally infected with francisella tularensis subsp. holarctica.an adult male hare (lepus brachyurus angustidens) was discovered in a moribund condition in the bush in the mountains of aomori prefecture in japan. upon gross inspection, many ticks were found on the neck and the external ear regions, and more than half the ticks contained blood in the intestine. the skin around the tick bite wounds was alopecic and mildly thickened. at necropsy, enlargement of the cervical lymph nodes and spleen were observed. histologically, acute necrotizing splenitis, lymph ...200920046031
the francisella tularensis pathogenicity island encodes a secretion system that is required for phagosome escape and virulence.francisella tularensis causes the human disease tularemia. f. tularensis is able to survive and replicate within macrophages, a trait that has been correlated with its high virulence, but it is unclear the exact mechanism(s) this organism uses to escape killing within this hostile environment. f. tularensis virulence is dependent upon the francisella pathogenicity island (fpi), a cluster of genes that we show here shares homology with type vi secretion gene clusters in vibrio cholerae and pseudo ...200920054881
[the lipoolygosaccharide o-antigen of francisella tularensis]. 200920063802
tularemia, plague, yersiniosis, and tyzzer's disease in wild rodents and lagomorphs in canada: a review.information related to infection of wild rodents or lagomorphs in canada by francisella tularensis, yersinia pestis, other yersinia spp., and clostridium piliforme was searched for this study. reports on tularemia in humans linked to these species came from diagnostic databases, literature, wildlife health specialists, and public health agencies. tularemia has been diagnosed in 8 species of wild rodent and 2 species in the genus lepus in canada. tularemia occurred in wild animals, or in humans a ...200920190973
vaccines against tularemia.francisella tularensis is a category a select agent for which vaccine and countermeasure development are a priority. in the past eight years, renewed interest in this pathogen has led to the generation of an enormous amount of new data on both the pathogen itself and its interaction with host cells. this information has fostered the development of various vaccine candidates including acellular subunit, killed whole cell and live attenuated. this review summarizes the progress and promise of thes ...200919923904
regulation of apoptosis and anti-apoptosis signalling by francisella tularensis.francisella tularensis induces apoptosis within macrophages but the temporal and spatial modulation through activation of caspase-1, caspase-3, and the anti-apoptosis nuclear transcription factor b (nf-kappab) is not known. whether escape of the bacteria into the cytosol is sufficient and/or essential for activation of nf-kappab is not known. our results show that f. tularensis subsp. novicida induces sustained nuclear translocation of nf-kappab at early time points after infection of human mono ...201019925880
restricted cytosolic growth of francisella tularensis subsp. tularensis by ifn-gamma activation of macrophages.the intracellular bacterium francisella tularensis ensures its survival and proliferation within phagocytes of the infected host through phagosomal escape and cytosolic replication, to cause the disease tularemia. the cytokine interferon-gamma (ifn-gamma) is important in controlling primary infections in vivo, and in vitro intracellular proliferation of francisella in macrophages, but its actual effects on the intracellular cycle of the bacterium are ambiguous. here, we have performed an extensi ...201019926654
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
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
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
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
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
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