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characterization of an endosymbiont infecting wood ticks, dermacentor andersoni, as a member of the genus francisella.a microorganism (dermacantor andersoni symbiont [das]) infecting rocky mountain wood ticks (d. andersoni) collected in the bitterroot mountains of western montana was characterized as an endosymbiont belonging to the genus francisella. previously described as wolbachia like, the organism's dna was amplified from both naturally infected tick ovarial tissues and vero cell cultures by pcr assay with primer sets derived from eubacterial 16s ribosomal dna (rdna) and francisella membrane protein genes ...19979327558
tularemia vaccines: recent developments and remaining hurdles.francisella tularensis subsp. tularensis is a facultative intracellular bacterial pathogen of humans and other mammals. its inhaled infectious dose is very low and can result in very high mortality. historically, subsp. tularensis was developed as a biological weapon and there are now concerns about its abuse as such by terrorists. a live attenuated vaccine developed pragmatically more than half a century ago from the less virulent holarctica subsp. is the sole prophylactic available, but it rem ...201121526941
tularemia in two cats.tularemia was diagnosed in 2 cats that were examined because of pyrexia and lethargy; both cats had a history of exposure to wild rabbits. one cat was vomiting, and the other was anorectic. physical examination revealed dehydration, lymphadenopathy, and hepatomegaly. hematologic and serum biochemical abnormalities included toxic neutrophils, high band neutrophil count, thrombocytopenia, and hyperbilirubinemia. diagnosis was confirmed by isolating francisella tularensis subsp tularensis from bone ...19989426784
multiple francisella tularensis subspecies and clades, tularemia outbreak, utah.in july 2007, a deer fly-associated outbreak of tularemia occurred in utah. human infections were caused by 2 clades (a1 and a2) of francisella tularensis subsp. tularensis. lagomorph carcasses from the area yielded evidence of infection with a1 and a2, as well as f. tularensis subsp. holarctica. these findings indicate that multiple subspecies and clades can cause disease in a localized outbreak of tularemia.200819046524
proteomic analysis of antibody response in a case of laboratory-acquired infection with francisella tularensis subsp. tularensis.immunoproteomic analysis was applied to study the immunoreactivity of serum samples collected at different time points from a laboratory assistant accidentally infected with highly virulent strain of francisella tularensis subsp. tularensis. immunoblotting showed that the spectrum of f. tularensis antigens recognized specifically by immune sera remained with the exception for 1 antigen stable for up to 16 years after infection. using immunoproteomics approach 10 immunoreactive antigens were succ ...200717575919
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
phagocytic receptors dictate phagosomal escape and intracellular proliferation of francisella tularensis.francisella tularensis, the causative agent of tularemia, survives and proliferates within macrophages of the infected host as part of its pathogenic strategy, through an intracellular life cycle that includes phagosomal escape and extensive proliferation within the macrophage cytosol. various in vitro models of francisella-macrophage interactions have been developed, using either opsonic or nonopsonic phagocytosis, and have generated discrepant results on the timing and extent of francisella ph ...201121422184
virulence differences among francisella tularensis subsp. tularensis clades in mice.francisella tularensis subspecies tularensis (type a) and holarctica (type b) are of clinical importance in causing tularemia. molecular typing methods have further separated type a strains into three genetically distinct clades, a1a, a1b and a2. epidemiological analyses of human infections in the united states suggest that a1b infections are associated with a significantly higher mortality rate as compared to infections caused by a1a, a2 and type b. to determine if genetic differences as define ...201020419133
regulation of virulence gene transcripts by the francisella novicida orphan response regulator pmra: role of phosphorylation and evidence of mgla/sspa interaction.francisella tularensis subsp. tularensis is the etiologic agent of tularemia and has been designated a category a biothreat agent by the cdc. tularemia is characterized by replication and dissemination within host phagocytes. intramacrophage growth is dependent upon the regulation of francisella pathogenicity island (fpi) virulence genes, which is poorly understood. two-component regulatory systems (tcs) are widely employed by gram-negative bacteria to monitor and respond to environmental signal ...201020231408
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
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
francisella tularensis induces extensive caspase-3 activation and apoptotic cell death in the tissues of infected mice.although francisella tularensis subsp. tularensis is known to cause extensive tissue necrosis, the pathogenesis of tissue injury has not been elucidated. to characterize cell death in tularemia, c57bl/6 mice were challenged by the intranasal route with type a f. tularensis, and the pathological changes in infected tissues were characterized over the next 4 days. at 3 days postinfection, well-organized inflammatory infiltrates developed in the spleen and liver following the spread of infection fr ...200919703976
novel genomic tools for specific and real-time detection of biothreat and frequently encountered foodborne pathogens.the bacterial genera escherichia, salmonella, shigella, vibrio, yersinia, and francisella include important food safety and biothreat agents. by extensive mining of the whole genome and protein databases of diverse, closely and distantly related bacterial species and strains, we have identified novel genome regions, which we utilized to develop a rapid detection platform for these pathogens. the specific genomic targets we have identified to design the primers in francisella tularensis subsp. tu ...201222488053
detection of a possible bioterrorism agent, francisella sp., in a clinical specimen by use of next-generation direct dna sequencing.deep sequencing detected a potential bioterrorism agent, francisella tularensis, in a human abscess sample (iwaki-08) of unknown etiology. identified single-nucleotide variations suggest that the iwaki-08 case was associated with francisella tularensis subsp. holarctica (biovar japonica) but not the highly virulent type a (francisella tularensis subsp. tularensis).201222337979
customizable pcr-microplate array for differential identification of multiple pathogens.customizable pcr-microplate arrays were developed for the rapid identification of salmonella typhimurium, salmonella saintpaul, salmonella typhi, shigella dysenteriae, escherichia coli o157:h7, francisella tularensis subsp. tularensis, francisella tularensis subsp. novicida, vibrio cholerae, vibrio parahaemolyticus, yersinia pestis, and yersinia pseudotuberculosis. previously, we identified highly specific primers targeting each of these pathogens. here, we report the development of customizable ...201324215700
phylogeography of francisella tularensis: global expansion of a highly fit clone.francisella tularensis contains several highly pathogenic subspecies, including francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. the phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (snp) analysis, high-density microarray snp genotyping, and real-time-pcr-based canonical snp (cansnp) assays. almost 30,000 snps were identified among 13 whole genomes for phylogenetic analysis ...200919251856
paralogous outer membrane proteins mediate uptake of different forms of iron and synergistically govern virulence in francisella tularensis tularensis.francisella tularensis subsp. tularensis is a highly infectious bacterium causing acute disease in mammalian hosts. mechanisms for the acquisition of iron within the iron-limiting host environment are likely to be critical for survival of this intracellular pathogen. fsle (ftt0025) and fupa (ftt0918) are paralogous proteins that are predicted to form β-barrels in the outer membrane of virulent strain schu s4 and are unique to francisella species. previous studies have implicated both fupa, initi ...201222661710
rapid dissemination of francisella tularensis and the effect of route of infection.francisella tularensis subsp. tularensis is classified as a category a bioweapon that is capable of establishing a lethal infection in humans upon inhalation of very few organisms. however, the virulence mechanisms of this organism are not well characterized. francisella tularensis subsp. novicida, which is an equally virulent subspecies in mice, was used in concert with a micropet scanner to better understand its temporal dissemination in vivo upon intranasal infection and how such disseminatio ...200819068128
identification of francisella tularensis subsp. tularensis a1 and a2 infections by real-time polymerase chain reaction.francisella tularensis subsp. tularensis (type a) is subdivided into clades a1 and a2. human tularemia infections caused by a1 and a2 differ with respect to clinical outcome; a1 infections are associated with a higher case fatality rate. in this study, we develop and evaluate taqman polymerase chain reaction (pcr) assays for identification of a1 and a2. both assays were shown to be specific to either a1 or a2, with sensitivities of 10 genomic equivalents. real-time pcr results for identification ...200919232853
genomic markers for differentiation of francisella tularensis subsp. tularensis a.i and a.ii strains.tularemia is caused by two subspecies of francisella tularensis, f. tularensis subsp. tularensis (type a) and f. tularensis subsp. holarctica (type b). f. tularensis subsp. tularensis is further subdivided into two genetically distinct populations (a.i and a.ii) that differ with respect to geographical location, anatomical source of recovered isolates, and disease outcome. using two human clinical isolates, suppression subtractive hybridization was performed to identify 13 genomic regions of dif ...200818024683
complete genomic characterization of a pathogenic a.ii strain of francisella tularensis subspecies tularensis.francisella tularensis is the causative agent of tularemia, which is a highly lethal disease from nature and potentially from a biological weapon. this species contains four recognized subspecies including the north american endemic f. tularensis subsp. tularensis (type a), whose genetic diversity is correlated with its geographic distribution including a major population subdivision referred to as a.i and a.ii. the biological significance of the a.i - a.ii genetic differentiation is unknown, th ...200717895988
identification of an essential francisella tularensis subsp. tularensis virulence factor.francisella tularensis, the highly virulent etiologic agent of tularemia, is a low-dose intracellular pathogen that is able to escape from the phagosome and replicate in the cytosol. although there has been progress in identifying loci involved in the pathogenicity of this organism, analysis of the genome sequence has revealed few obvious virulence factors. we previously reported isolation of an f. tularensis subsp. tularensis strain schu s4 transposon insertion mutant with a mutation in a predi ...200918981253
francisella tularensis subsp. tularensis schu s4 disulfide bond formation protein b, but not an rnd-type efflux pump, is required for virulence.francisella tularensis subsp. tularensis is a highly virulent bacterium that is a cdc select agent. despite advancements in the understanding of its biology, details pertaining to virulence are poorly understood. in previous work, we identified a transposon insertion mutant in the ftt0107c locus that was defective in intracellular survival in hepg2 and j77a.1 cells. here, we report that this mutant was also highly attenuated in vivo. the ftt0107c locus is predicted to encode an ortholog of the d ...200818458069
coactivating signals for the hepatic lymphocyte gamma interferon response to francisella tularensis.the facultative intracellular bacterium francisella tularensis is capable of causing systemic infections in various hosts, including mice and humans. the liver is a major secondary site of f. tularensis infection, but hepatic immune responses to the pathogen remain poorly defined. immune protection against the pathogen is thought to depend on the cytokine gamma interferon (ifn-gamma), but the cellular basis for this response has not been characterized. here we report that natural killer cells fr ...200717178781
paired-end sequence mapping detects extensive genomic rearrangement and translocation during divergence of francisella tularensis subsp. tularensis and francisella tularensis subsp. holarctica populations.comparative genome hybridization of the francisella tularensis subsp. tularensis and f. tularensis subsp. holarctica populations have shown that genome content is highly conserved, with relatively few genes in the f. tularensis subsp. tularensis genome being absent in other f. tularensis subspecies. to determine if organization of the genome differs between global populations of f. tularensis subsp. tularensis and f. tularensis subsp. holarctica, we have used paired-end sequence mapping (pesm) t ...200616885459
comparative proteome analysis of fractions enriched for membrane-associated proteins from francisella tularensis subsp. tularensis and f. tularensis subsp. holarctica strains.the facultative intracellular pathogen francisella tularensis is the causative agent of the serious infectious disease tularemia. despite intensive research, the virulence factors and pathogenetic mechanisms remain largely unknown. to identify novel putative virulence factors, we carried out a comparative proteome analysis of fractions enriched for membrane-associated proteins isolated from the highly virulent subspecies tularensis strain schu s4 and three representatives of subspecies holarctic ...200617081064
localized cutaneous infection with francisella tularensis resembling ulceroglandular tularemia in a cat.a chronically draining subcutaneous mass was removed from the ventral cervical region of a 6-year-old spayed female domestic shorthair cat. the histopathologic diagnosis was severe locally extensive pyogranulomatous and necrotizing cellulitis. bacterial culture yielded francisella tularensis subsp. tularensis as the causative agent. immunohistochemical evaluation of sections for f. tularensis was negative. one year later, the cat was euthanized because of progressive lethargy found to be due to ...200414974853
genetic tools for highly pathogenic francisella tularensis subsp. tularensis.this paper is the first detailed description of the development and use of new genetic tools specifically for the safe manipulation of highly pathogenic francisella tularensis subsp. tularensis. most of these tools are also demonstrated to work with other f. tularensis subspecies. kanamycin and hygromycin resistance determinants that function as genetic markers in f. tularensis subsp. tularensis strain schu and sets of episomal shuttle vectors that are either unstable or stably maintained in the ...200617074911
detection of francisella tularensis in biological specimens using a capture enzyme-linked immunosorbent assay, an immunochromatographic handheld assay, and a pcr.the early detection of francisella tularensis, the causative agent of tularemia, is important for adequate treatment by antibiotics and the outcome of the disease. here we describe a new capture enzyme-linked immunosorbent assay (celisa) based on monoclonal antibodies specific for lipopolysaccharide (lps) of francisella tularensis subsp. holarctica and francisella tularensis subsp. tularensis. no cross-reactivity with francisella tularensis subsp. novicida, francisella philomiragia, and a panel ...200010618283
the immunologically distinct o antigens from francisella tularensis subspecies tularensis and francisella novicida are both virulence determinants and protective antigens.we have determined the sequence of the gene cluster encoding the o antigen in francisella novicida and compared it to the previously reported o-antigen cluster in francisella tularensis subsp. tularensis. immunization with purified lipopolysaccharide (lps) from f. tularensis subsp. tularensis or f. novicida protected against challenge with francisella tularensis subsp. holarctica and f. novicida, respectively. the lps from f. tularensis subsp. tularensis did not confer protection against challen ...200717074846
o-linked glycosylation of the pila pilin protein of francisella tularensis: identification of the endogenous protein-targeting oligosaccharyltransferase and characterization of the native oligosaccharide.findings from a number of studies suggest that the pila pilin proteins may play an important role in the pathogenesis of disease caused by species within the genus francisella. as such, a thorough understanding of pila structure and chemistry is warranted. here, we definitively identified the pgla protein-targeting oligosaccharyltransferase by virtue of its necessity for pila glycosylation in f. tularensis and its sufficiency for pila glycosylation in escherichia coli. in addition, we used mass ...201121804002
glycosylation of dsba in francisella tularensis subspecies tularensis.in francisella tularensis subspecies tularensis, dsba has been shown to be an essential virulence factor and has been observed to migrate to multiple protein spots in two dimensional electrophoresis gels. in this work, we show that the protein is modified with a 1156 da glycan moiety in o-linkage. mass spectrometry studies suggest the glycan is a hexasaccharide, comprised of n-acetyl hexosamines, hexoses and an unknown monosaccharide. disruption of two genes within the ftt0789-ftt0800 putative p ...201121803994
a mutant of francisella tularensis strain schu s4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine.francisella tularensis subsp. tularensis (type a) strain schu s4 is a prototypic strain of the pathogen that is highly virulent for humans and other mammals. its intradermal (i.d.) 50% lethal dose (ld50) for mice is <10 cfu. we discovered a spontaneous mutant, designated fsc043, of schu s4 with an i.d. ld50 of >10(8) cfu. fsc043 effectively vaccinated mice against challenge with a highly virulent type a strain, and the protective efficacy was at least as good as that of f. tularensis lvs, an emp ...200516299332
characterization of the o antigen gene cluster and structural analysis of the o antigen of francisella tularensis subsp. tularensis.a gene cluster encoding enzymes involved in lps o antigen biosynthesis was identified from the partial genome sequence of francisella tularensis subsp. tularensis schu s4. all of the genes within the cluster were assigned putative functions based on sequence similarity with genes from o antigen biosynthetic clusters from other bacteria. ten pairs of overlapping primers were designed to amplify the o antigen biosynthetic cluster by pcr from nine strains of f. tularensis. although the gene cluster ...200312972577
revisiting the gram-negative lipoprotein paradigm.the processing of lipoproteins (lpps) in gram-negative bacteria is generally considered an essential pathway. mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by lnt, an apolipoprotein n-acyltransferase. the mature lipoproteins are then sorted by the lol system, with most lpps inserted into the outer membrane (om). we demonstrate here that the lnt gene is not essential to the gram-negative pathogen francisella tularensis subsp. tularensis strain ...201525755189
first isolation of francisella tularensis subsp. tularensis in europe.francisella tularensis subsp. tularensis is the common causal agent of tularemia in the usa and canada, while f. tularensis subsp. palaearctica (holarctica) occurs in europe, asia, and to a minor extent in north america. f. tularensis subsp. mediaasiatica was found only in central asia in a part of the former soviet union. of the total of 155 f. tularensis strains isolated over the years 1978-1996 during the surveillance of tularemia in slovakia, 65 were from small mammals, 68 from ticks and 22 ...19989928875
outer membrane vesicles displaying engineered glycotopes elicit protective antibodies.the o-antigen polysaccharide (o-ps) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a b-cell antigen. antibodies elicited by o-ps often confer protection against infection; therefore, o-ps glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. however, conventional methods for natural extraction or chemical synthesis of o-ps are technically demanding, inefficient, and expensive. here, we describe an a ...201627274048
a δclpb mutant of francisella tularensis subspecies holarctica strain, fsc200, is a more effective live vaccine than f. tularensis lvs in a mouse respiratory challenge model of tularemia.francisella tularensis subsp. tularensis is a highly virulent pathogen for humans especially if inhaled. consequently, it is considered to be a potential biothreat agent. an experimental vaccine, f. tularensis live vaccine strain, derived from the less virulent subsp. holarctica, was developed more than 50 years ago, but remains unlicensed. previously, we developed a novel live vaccine strain, by deleting the chaperonin clpb gene from f. tularensis subsp. tularensis strain, schu s4. schu s4δclpb ...201324236032
igle is an outer membrane-associated lipoprotein essential for intracellular survival and murine virulence of type a francisella tularensis.igle is a small, hypothetical protein encoded by the duplicated francisella pathogenicity island (fpi). inactivation of both copies of igle rendered francisella tularensis subsp. tularensis schu s4 avirulent and incapable of intracellular replication, owing to an inability to escape the phagosome. this defect was fully reversed following single-copy expression of igle in trans from atttn7 under the control of the francisella rpsl promoter, thereby establishing that the loss of igle, and not pola ...201323959721
disruption of francisella tularensis schu s4 igli, iglj, and pdpc genes results in attenuation for growth in human macrophages and in vivo virulence in mice and reveals a unique phenotype for pdpc.francisella tularensis is a facultative intracellular bacterial pathogen and the causative agent of tularemia. after infection of macrophages, the organism escapes from its phagosome and replicates to high density in the cytosol, but the bacterial factors required for these aspects of virulence are incompletely defined. here, we describe the isolation and characterization of francisella tularensis subsp. tularensis strain schu s4 mutants that lack functional igli, iglj, or pdpc, three genes of t ...201223275090
pang, a new ketopantoate reductase involved in pantothenate synthesis.pantothenate, commonly referred to as vitamin b(5), is an essential molecule in the metabolism of living organisms and forms the core of coenzyme a. unlike humans, some bacteria and plants are capable of de novo biosynthesis of pantothenate, making this pathway a potential target for drug development. francisella tularensis subsp. tularensis schu s4 is a zoonotic bacterial pathogen that is able to synthesize pantothenate but is lacking the known ketopantoate reductase (kpr) genes, pane and ilvc, ...201323243306
kdo hydrolase is required for francisella tularensis virulence and evasion of tlr2-mediated innate immunity.the highly virulent francisella tularensis subsp. tularensis has been classified as a category a bioterrorism agent. a live vaccine strain (lvs) has been developed but remains unlicensed in the united states because of an incomplete understanding of its attenuation. lipopolysaccharide (lps) modification is a common strategy employed by bacterial pathogens to avoid innate immunity. a novel modification enzyme has recently been identified in f. tularensis and helicobacter pylori. this enzyme, a tw ...201323404403
fipb, an essential virulence factor of francisella tularensis subsp. tularensis, has dual roles in disulfide bond formation.fipb, an essential virulence factor of francisella tularensis, is a lipoprotein with two conserved domains that have similarity to disulfide bond formation a (dsba) proteins and the amino-terminal dimerization domain of macrophage infectivity potentiator (mip) proteins, which are proteins with peptidyl-prolyl cis/trans isomerase activity. this combination of conserved domains is unusual, so we further characterized the enzymatic activity and the importance of the mip domain and lipid modificatio ...201425092026
identification of mechanisms for attenuation of the fsc043 mutant of francisella tularensis schu s4.previously, we identified a spontaneous, essentially avirulent mutant, fsc043, of the highly virulent strain schu s4 of francisella tularensis subsp. tularensis. we have now characterized the phenotype of the mutant and the mechanisms of its attenuation in more detail. genetic and proteomic analyses revealed that the pdpe gene and most of the pdpc gene were very markedly downregulated and, as previously demonstrated, that the strain expressed partially deleted and fused fupa and fupb genes. fsc0 ...201424935978
purification and biophysical characterization of the capa membrane protein ftt0807 from francisella tularensis.the capa gene (ftt0807) from francisella tularensis subsp. tularensis schu s4 encodes a 44.4 kda integral membrane protein composed of 403 amino acid residues that is part of an apparent operon that encodes at least two other membrane proteins, capb, and capc, which together play a critical role in the virulence and pathogenesis of this bacterium. the capa gene was overexpressed in escherichia coli as a c-terminal his6-tagged fusion with a folding reporter green fluorescent protein (frgfp). puri ...201424593131
requirement of the cxxc motif of novel francisella infectivity potentiator protein b fipb, and fipa in virulence of f. tularensis subsp. tularensis.the lipoprotein encoded by the francisella tularensis subsp. tularensis locus ftt1103 is essential for virulence; an ftt1103 deletion mutant is defective in uptake and intracellular survival, and mice survive high dose challenges of greater than 10(8) bacteria. this protein has two conserved domains; one is found in a class of virulence proteins called macrophage infectivity potentiator (mip) proteins, and the other in oxidoreductase disulfide bond formation protein a (dsba)-related proteins. we ...201121931773
francisella tularensis subsp. tularensis group a.i, united states.we used whole-genome analysis and subsequent characterization of geographically diverse strains using new genetic signatures to identify distinct subgroups within francisella tularensis subsp. tularensis group a.i: a.i.3, a.i.8, and a.i.12. these subgroups exhibit complex phylogeographic patterns within north america. the widest distribution was observed for a.i.12, which suggests an adaptive advantage.201424755401
francisella tularensis subsp. tularensis induces a unique pulmonary inflammatory response: role of bacterial gene expression in temporal regulation of host defense responses.pulmonary exposure to francisella tularensis is associated with severe lung pathology and a high mortality rate. the lack of induction of classical inflammatory mediators, including il1-β and tnf-α, during early infection has led to the suggestion that f. tularensis evades detection by host innate immune surveillance and/or actively suppresses inflammation. to gain more insight into the host response to francisella infection during the acute stage, transcriptomic analysis was performed on lung t ...201323690939
comparative transcriptional analyses of francisella tularensis and francisella novicida.francisella tularensis is composed of a number of subspecies with varied geographic distribution, host ranges, and virulence. in view of these marked differences, comparative functional genomics may elucidate some of the molecular mechanism(s) behind these differences. in this study a shared probe microarray was designed that could be used to compare the transcriptomes of francisella tularensis subsp. tularensis schu s4 (ftt), francisella tularensis subsp. holarctica or960246 (fth), francisella ...201627537327
detection of anthrax and other pathogens using a unique liquid array technology.a bead-based liquid hybridization assay, luminex(®) 100™, was used to identify four pathogenic bacteria, bacillus anthracis, clostridium botulinum, francisella tularensis subsp. tularensis, and yersinia pestis, and several close relatives. hybridization between pcr-amplified target sequences and probe sequences (located within the 23s ribosomal rna gene rrl and the genes related to the toxicity of each bacterium) was detected in single-probe or multiple-probe assays, depending on the organism. t ...201424147813
proteogenomic biomarkers for identification of francisella species and subspecies by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.francisella tularensis is the causative agent of tularemia. because some francisella strains are very virulent, this species is considered by the centers for disease control and prevention to be a potential category a bioweapon. a mass spectrometry method to quickly and robustly distinguish between virulent and nonvirulent francisella strains is desirable. a combination of shotgun proteomics and whole-cell matrix-assisted laser desorption ionization-time-of-flight (maldi-tof) mass spectrometry o ...201425215633
zinc acquisition mechanisms differ between environmental and virulent francisella species.zinc is an essential nutrient for bacterial growth. because host cells can restrict pathogen access to zinc as an antimicrobial defense mechanism, intracellular pathogens such as francisella must sense their environment and acquire zinc in response. in many bacteria, the conserved transcription factor zur is a key regulator of zinc acquisition. to identify mechanisms of zinc uptake in francisella novicida u112, transcriptome sequencing of wild-type and putative zur mutant bacteria was performed. ...201829109188
expansion and retention of pulmonary cd4(+) t cells after prime boost vaccination correlates with improved longevity and strength of immunity against tularemia.francisella tularensis subsp. tularensis strain schus4 (ftt) is a highly virulent intracellular bacterium. inhalation of 10 or fewer organisms results in an acute and potentially lethal disease called pneumonic tularemia. ftt infections occur naturally in the u.s. and ftt was developed as a bioweapon. thus, there is a need for vaccines that protect against this deadly pathogen. although a live vaccine strain of francisella tularensis (lvs) exists, lvs fails to generate long-lived protective immu ...201728372827
host-pathogen o-methyltransferase similarity and its specific presence in highly virulent strains of francisella tularensis suggests molecular mimicry.whole genome comparative studies of many bacterial pathogens have shown an overall high similarity of gene content (>95%) between phylogenetically distinct subspecies. in highly clonal species that share the bulk of their genomes subtle changes in gene content and small-scale polymorphisms, especially those that may alter gene expression and protein-protein interactions, are more likely to have a significant effect on the pathogen's biology. in order to better understand molecular attributes tha ...201121637805
whole genome transcriptomics reveals global effects including up-regulation of francisella pathogenicity island gene expression during active stringent response in the highly virulent francisella tularensis subsp. tularensis schu s4.during conditions of nutrient limitation bacteria undergo a series of global gene expression changes to survive conditions of amino acid and fatty acid starvation. rapid reallocation of cellular resources is brought about by gene expression changes coordinated by the signalling nucleotides' guanosine tetraphosphate or pentaphosphate, collectively termed (p)ppgpp and is known as the stringent response. the stringent response has been implicated in bacterial virulence, with elevated (p)ppgpp level ...201729034854
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