Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| a sensitive liquid chromatography/mass spectrometry-based assay for quantitation of amino-containing moieties in lipid a. | a novel sensitive liquid chromatography/mass spectrometry-based assay was developed for the quantitation of aminosugars, including 2-amino-2-deoxyglucose (glucosamine, glcn), 2-amino-2-deoxygalactose (galactosamine, galn), and 4-amino-4-deoxyarabinose (aminoarabinose, aran), and for ethanolamine (etn), present in lipid a. this assay enables the identification and quantitation of all amino-containing moieties present in lipopolysaccharide or lipid a from a single sample. the method was applied to ... | 2009 | 19130491 |
| iron transport in francisella in the absence of a recognizable tonb protein still requires energy generated by the proton motive force. | the mechanism of iron transport in francisella is still a puzzle since none of the sequenced francisella strains appears to encode a tonb protein, the energy transducer of the proton motive force necessary to act on the bacterial outer membrane siderophore receptor to allow the internalization of iron. in this work we demonstrate using kinetic experiments of radioactive fe(3+) utilization, that iron uptake in francisella novicida, although with no recognizable tonb protein, is indeed dependent o ... | 2009 | 18946633 |
| francisella tularensis: an arthropod-borne pathogen. | arthropod transmission of tularemia occurs throughout the northern hemisphere. few pathogens show the adaptability of francisella tularensis to such a wide array of arthropod vectors. nonetheless, arthropod transmission of f. tularensis was last actively investigated in the first half of the 20th century. this review will focus on arthropod transmission to humans with respect to vector species, modes of transmission, geographic differences and f. tularensis subspecies and clades. | 2009 | 18950590 |
| electrical microarrays for highly sensitive detection of multiplex pcr products from biological agents. | for the sensitive detection of amplicons derived from diagnostic pcr, a novel electrical low-density microarray is applied and compared to state-of-the-art quantitative real-time pcr. the principle of the electrochemical method and the effective use for analysis are described. interdigitated array gold electrodes (ida-e) embedded into a silicon chip are the core technology of the fully automated compact biosensor system, basing on enzyme coupled electrochemical detection. the biointerface is bui ... | 2009 | 18954971 |
| genome-wide screen in francisella novicida for genes required for pulmonary and systemic infection in mice. | francisella tularensis is a gram-negative, highly infectious, aerosolizable facultative intracellular pathogen that causes the potentially life-threatening disease tularemia. to date there is no approved vaccine available, and little is known about the molecular mechanisms important for infection, survival, and dissemination at different times of infection. we report the first whole-genome screen using an inhalation mouse model to monitor infection in the lung and dissemination to the liver and ... | 2009 | 18955478 |
| inferring genomic flux in bacteria. | acquisition and loss of genetic material are essential forces in bacterial microevolution. they have been repeatedly linked with adaptation of lineages to new lifestyles, and in particular, pathogenicity. comparative genomics has the potential to elucidate this genetic flux, but there are many methodological challenges involved in inferring evolutionary events from collections of genome sequences. here we describe a model-based method for using whole-genome sequences to infer the patterns of gen ... | 2009 | 19015321 |
| an optimized, multiplexed multi-locus variable-number tandem repeat analysis system for genotyping francisella tularensis. | we present a truncated, optimized, multiplexed multiple-locus variable-number tandem repeat analysis system for the molecular subtyping of francisella tularensis that reduces time and cost requirements while retaining high discriminatory power. | 2009 | 19018964 |
| cellular and humoral immunity are synergistic in protection against types a and b francisella tularensis. | herein we report studies with a novel combination vaccine that, when administered to mice, conferred protection against highly virulent strains of francisella tularensis by stimulating both arms of the immune system. our earlier studies with ft.lvs::wbta, an o-polysaccharide (ops)-negative mutant derived from the available live vaccine strain of f. tularensis (ft.lvs), elucidated the role of antibodies to the ops - a key virulence determinant - in protection against virulent type a organisms. ho ... | 2009 | 19022323 |
| francisella tularensis regulates autophagy-related host cell signaling pathways. | the gram-negative intracellular pathogen francisella tularensis is known for its ability to dampen host immune responses. we recently performed a microarray analysis comparing human monocyte responses to the highly virulent f. tularensis tularensis schu s4 strain (f.t.) versus the less virulent f. tularensis novicida (f.n.).(1) many groups of genes were affected, including those involved with autophagy and with the regulation of autophagy. here, we discuss the implications in the context of fran ... | 2009 | 19029814 |
| glycogen synthase kinase-3beta (gsk3beta) inhibition suppresses the inflammatory response to francisella infection and protects against tularemia in mice. | francisella tularensis, the causative agent of tularemia, is currently considered a category a bioterrorism agent due to its high virulence. infection with f. tularensis results in an inflammatory response that plays an important role in the pathogenesis of the disease; however, the cellular mechanisms regulating this response are poorly understood. glycogen synthase kinase-3beta (gsk3beta) is a serine/threonine protein kinase that has recently emerged as a key regulatory switch in the modulatio ... | 2009 | 18929413 |
| host immune response and acute disease in a zebrafish model of francisella pathogenesis. | members of the bacterial genus francisella are highly virulent and infectious pathogens. new models to study francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. we took advantage of the recent discovery of a novel species of francisella to establish a zebrafish/francisella comparative model of pathogenesis and host immune response. adult zebrafish were susceptib ... | 2009 | 19047404 |
| pathology of inhalational francisella tularensis spp. tularensis schu s4 infection in african green monkeys (chlorocebus aethiops). | tularemia, caused by francisella tularensis, is a sporadic zoonotic disease with the potential to be an agent of biowarfare or bioterrorism. we describe here the gross, histologic, immunohistochemical, and ultrastructural findings in a group of 5 african green monkeys (agms) that received an average inhaled dose of 729 colony-forming units of f. tularensis and died or were euthanatized between days 7 and 11 post infection. clinical changes were evident by 48 hours post infection, and key physiol ... | 2009 | 19276059 |
| single-copy chromosomal integration systems for francisella tularensis. | francisella tularensis is a fastidious gram-negative bacterium responsible for the zoonotic disease tularemia. investigation of the biology and molecular pathogenesis of f. tularensis has been limited by the difficulties in manipulating such a highly pathogenic organism and by a lack of genetic tools. however, recent advances have substantially improved the ability of researchers to genetically manipulate this organism. to expand the molecular toolbox we have developed two systems to stably inte ... | 2009 | 19332817 |
| cervical tularaemia in a non-endemic area. | tularemia is a zoonotic disease caused by francisella tularensis. the microorganism is transmitted to humans by contact with, or ingestion of, infected animal tissues, by insect bites, consumption of contaminated food or water, or from inhalation of aerolized bacteria. in this report we describe a case of tularemia presenting with multiple cervical lymphadenitis in asturias (spain). final diagnosis was established based on a serological test. the patient was successfully managed with surgery and ... | 2009 | 19333186 |
| establishment of lethal inhalational infection with francisella tularensis (tularaemia) in the common marmoset (callithrix jacchus). | susceptibility and lethality studies of inhalational tularaemia were undertaken using the common marmoset (callithrix jacchus) to determine its suitability as a non-human primate model. pairs of marmosets were exposed to varying challenge doses of francisella tularensis by the airborne route and monitored for up to 14 days postchallenge (p.c.). lethal infection was achieved following a retained dose of less than 10 bacterial colony-forming units (cfu). however, precise ld(50) determination was n ... | 2009 | 19335549 |
| virulence and pathogenicity of francisella philomiragia subsp. noatunensis for atlantic cod, gadus morhua l., and laboratory mice. | 2009 | 19335614 | |
| differential requirements for protection against mucosal challenge with francisella tularensis in the presence versus absence of cholera toxin b and inactivated f. tularensis. | francisella tularensis is a category a biothreat agent for which there is no approved vaccine and the correlates of protection are not well understood. in particular, the relationship between the humoral and cellular immune response to f. tularensis and the relative importance of each in protection is controversial. yet, understanding this relationship will be crucial to the development of an effective vaccine against this organism. we demonstrate, for the first time, a differential requirement ... | 2009 | 19342669 |
| an 8-year-old boy with fever, axillary ulcerative lesion, and altered mental status. | 2009 | 19344255 | |
| francisella tularensis directly interacts with the endothelium and recruits neutrophils with a blunted inflammatory phenotype. | francisella tularensis, the causative agent of tularemia, is a highly virulent organism, especially when exposure occurs by inhalation. recent data suggest that francisella interacts directly with alveolar epithelial cells. although f. tularensis causes septicemia and can live extracellularly in a murine infection model, there is little information about the role of the vascular endothelium in the host response. we hypothesized that f. tularensis would interact with pulmonary endothelial cells a ... | 2009 | 19346432 |
| identification of migr, a regulatory element of the francisella tularensis live vaccine strain iglabcd virulence operon required for normal replication and trafficking in macrophages. | francisella tularensis, the etiological agent of tularemia, is capable of infecting a wide range of animals and causes a severe, lethal disease in humans. the pathogen evades killing by cells of the innate immune system utilizing genes encoding a pathogenicity island, including iglabcd, and instead utilizes these cells as a niche for replication and dissemination to other organs within the host. regulators of the igl genes (e.g., mgla, sspa, fevr and pmra) have been identified, but environmental ... | 2009 | 19349423 |
| francisella-like endosymbiont dna and francisella tularensis virulence-related genes in brazilian ticks (acari: ixodidae). | ticks are vectors of a variety of pathogens, including francisella tularensis. bacteria in the genus francisella have been identified mostly in the northern hemisphere and include tick endosymbionts. francisella has never been described in brazil, where amblyomma spp. ticks are known as the vector of many bacterial zoonotic pathogens. in the present work, we have identified bacterial dna sequences with identity to francisella genes in amblyomma dubitatum neumann dermacentor nitens (neumann), and ... | 2009 | 19351090 |
| lethal pulmonary infection with francisella novicida causes depletion of alphabeta t cells from lungs. | respiratory francisella infections induce a delayed innate immune response followed by a severe sepsis like condition. in this study, mice infected intranasally with francisella novicida showed a depletion of alphabeta t cells in lungs while exhibiting large accumulations of other leukocytes correlating with disease severity. the depleted t cells were predominantly cd4(+). the alphabeta t cells in infected mice showed significantly higher levels of annexin v binding than those in mock control mi ... | 2009 | 19356746 |
| tularemic meningitis in the united states. | tularemia is a zoonotic disease caused by francisella tularensis. tularemia presents with various clinical illnesses, but meningitis is rare. | 2009 | 19364939 |
| characterization of rationally attenuated francisella tularensis vaccine strains that harbor deletions in the guaa and guab genes. | francisella tularensis, the etiologic agent of tularemia, can cause severe and fatal infection after inhalation of as few as 10 -- 100cfu. f. tularensis is a potential bioterrorism agent and, therefore, a priority for countermeasure development. vaccination with the live vaccine strain (lvs), developed from a type b strain, confers partial protection against aerosal exposure to the more virulent type a strains and provides proof of principle that a live attenuated vaccine strain may be efficacio ... | 2009 | 19368784 |
| life on the inside: the intracellular lifestyle of cytosolic bacteria. | bacterial pathogens exploit a huge range of niches within their hosts. many pathogens can invade non-phagocytic cells and survive within a membrane-bound compartment. however, only a small number of bacteria, including listeria monocytogenes, shigella flexneri, burkholderia pseudomallei, francisella tularensis and rickettsia spp., can gain access to and proliferate within the host cell cytosol. here, we discuss the mechanisms by which these cytosolic pathogens escape into the cytosol, obtain nut ... | 2009 | 19369949 |
| characterization of the pathogenicity island protein pdpa and its role in the virulence of francisella novicida. | francisella tularensis is a highly virulent, intracellular pathogen that causes the disease tularaemia. a research surrogate for f. tularensis is francisella novicida, which causes a tularaemia-like disease in mice, grows similarly in macrophages, and yet is unable to cause disease in humans. both francisella species contain a cluster of genes referred to as the francisella pathogenicity island (fpi). pathogenicity determinant protein a (pdpa), encoded by the pdpa gene, is located within the fpi ... | 2009 | 19372153 |
| a francisella novicida pdpa mutant exhibits limited intracellular replication and remains associated with the lysosomal marker lamp-1. | several genes contained in the francisella pathogenicity island (fpi) encode proteins needed for intracellular growth and virulence of francisella tularensis. the pdpa gene is the first cistron in the larger of the two operons found in the fpi. in this work we studied the intracellular growth phenotype of a francisella novicida mutant in the pdpa gene. the deltapdpa strain was capable of a small amount of intracellular replication but, unlike wild-type f. novicida, remained associated with the l ... | 2009 | 19372155 |
| intracellular biology and virulence determinants of francisella tularensis revealed by transcriptional profiling inside macrophages. | summary the highly infectious bacterium francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. here we have performed a global transcriptional profiling of the highly virulent f. tularensis ssp. tularensis schu s4 strain during its intracellular cycle within primary murine macrophages, to characterize its intracellular biology and identify pathogenic determinants based on their intracellular expression prof ... | 2009 | 19388904 |
| targeted gene disruption in francisella tularensis by group ii introns. | francisella tularensis is a highly infectious gram-negative bacterium that is the causative agent of tularemia. very little is known about the molecular mechanisms responsible for f. tularensis virulence, in part due to the paucity of genetic tools available for the study of f. tularensis. we have developed a gene knockout system for f. tularensis that utilizes retargeted mobile group ii introns, or "targetrons". these targetrons disrupt both single and duplicated target genes at high efficiency ... | 2009 | 19398003 |
| tularemia in germany: the tip of the iceberg? | tularemia is a rare, notifiable zoonosis in germany. since november 2004, several lines of evidence including outbreaks in humans or animals and confirmed infections in indigenous hare and rodent populations have indicated a re-emergence of tularemia in different german federal states. unfortunately, reliable basic information on the seroprevalence in different geographical regions, permitting the identification of risk factors, does not exist. combining a sensitive screening assay with a highly ... | 2009 | 18808726 |
| artificial plasmid engineered to simulate multiple biological threat agents. | the objective of this study was to develop a non-virulent simulant to replace several virulent organisms during the development of detection and identification methods for biological threat agents. we identified and selected specific genes to detect yersinia pestis, francisella tularensis, burkholderia mallei, burkholderia pseudomallei, rickettsia sp., coxiella burnetii, brucella sp., enterohemorrhagic escherichia coli o157:h7, bacillus anthracis, and variola (smallpox) virus. we then designed a ... | 2009 | 18923830 |
| discovery of new biosynthetic pathways: the lipid a story. | the outer monolayer of the outer membrane of gram-negative bacteria consists of the lipid a component of lipopolysaccharide (lps), a glucosamine-based saccharolipid that is assembled on the inner surface of the inner membrane. the first six enzymes of the lipid a pathway are required for bacterial growth and are excellent targets for the development of new antibiotics. following assembly, the abc transporter msba flips nascent lps to the periplasmic side of the inner membrane, whereupon addition ... | 2009 | 18974037 |
| direct and indirect impairment of human dendritic cell function by virulent francisella tularensis schu s4. | the gram-negative, facultative intracellular bacterium francisella tularensis causes acute, lethal pneumonic disease following infection with only 10 cfu. the mechanisms used by the bacterium to accomplish this in humans are unknown. here, we demonstrate that virulent, type a f. tularensis strain schu s4 efficiently infects and replicates in human myeloid dendritic cells (dcs). despite exponential replication over time, schu s4 failed to stimulate transforming growth factor beta, interleukin-10 ... | 2009 | 18981246 |
| 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 ... | 2009 | 18981253 |
| nk cells activated in vivo by bacterial dna control the intracellular growth of francisella tularensis lvs. | we demonstrated previously that mice treated with bacterial or oligonucleotide dna containing unmethylated cpg motifs are transiently protected against lethal parenteral challenge with the intracellular bacterium francisella tularensis live vaccine strain (lvs). here we explore the cellular basis of this protection. wild-type mice that were treated with cpg oligonucleotide dna and challenged with a lethal dose of lvs survived, while mice lacking tlr9 did not. in vitro, treatment of lvs-infected ... | 2009 | 18992838 |
| francisella inhibits stat1-mediated signaling in macrophages and prevents activation of antigen-specific t cells. | signal transducer and activator of transcription-1 (stat1) signaling mediate most biological functions of ifnalpha, ifnbeta and ifngamma although recent studies indicate that ifngamma can alter expression of several genes via a stat1-independent pathway. stat1 is critical for immunity against a variety of intracellular pathogens and some studies show that pathogens evade host immunity by interfering with stat1 signaling. here, we have investigated the role of stat1 in host defense against pulmon ... | 2009 | 19001470 |
| classification of select category a and b bacteria by fourier transform infrared spectroscopy. | fourier transform infrared (ft-ir) spectroscopy historically is a powerful tool for the taxonomic classification of bacteria by genus, species, and strain when they are grown under carefully controlled conditions. relatively few reports have investigated the determination and classification of pathogens such as the national institute of allergy and infectious diseases (niaid) category a bacillus anthracis spores and cells (ba), yersinia species, francisella tularensis (ft), and category b brucel ... | 2009 | 19146715 |
| glutathione provides a source of cysteine essential for intracellular multiplication of francisella tularensis. | francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. its ability to multiply and survive in macrophages is critical for its virulence. by screening a bank of himarft transposon mutants of the f. tularensis live vaccine strain (lvs) to isolate intracellular growth-deficient mutants, we selected one mutant in a gene encoding a putative gamma-glutamyl transpeptidase (ggt). this gene (ftl_0766) was hence designated ggt. the mutant strain showed impaired int ... | 2009 | 19158962 |
| biosynthesis of undecaprenyl phosphate-galactosamine and undecaprenyl phosphate-glucose in francisella novicida. | lipid a of francisella tularensis subsp. novicida contains a galactosamine (galn) residue linked to its 1-phosphate group. as shown in the preceding paper, this galn unit is transferred to lipid a from the precursor undecaprenyl phosphate-beta-d-galn. a small portion of the free lipid a of francisella novicida is further modified with a glucose residue at position-6'. we now demonstrate that the two f. novicida homologues of escherichia coli arnc, designated flmf1 and flmf2, are essential for li ... | 2009 | 19166326 |
| identification of undecaprenyl phosphate-beta-d-galactosamine in francisella novicida and its function in lipid a modification. | francisella tularensis is a highly infectious pathogen that causes tularemia. francisella lipid a contains an unusual galactosamine (galn) unit, attached to its 1-phosphate moiety. two genes, flmf2 and flmk, are required for the addition of galn to francisella lipid a, but the relevant enzymes and the galn donor substrate have not been characterized. we now report the purification and identification of a novel minor lipid from francisella novicida that functions as the galn donor. on the basis o ... | 2009 | 19166327 |
| francisella tularensis infection-derived monoclonal antibodies provide detection, protection, and therapy. | francisella tularensis is the causative agent of tularemia and a potential agent of biowarfare. as an easily transmissible infectious agent, rapid detection and treatment are necessary to provide a positive clinical outcome. as an agent of biowarfare, there is an additional need to prevent infection. we made monoclonal antibodies to the f. tularensis subsp. holarctica live vaccine strain (f. tularensis lvs) by infecting mice with a sublethal dose of bacteria and, following recovery, by boosting ... | 2009 | 19176692 |
| elevation of francisella philomiragia subsp. noatunensis mikalsen et al. (2007) to francisella noatunensis comb. nov. [syn. francisella piscicida ottem et al. (2008) syn. nov.] and characterization of francisella noatunensis subsp. orientalis subsp. nov., two important fish pathogens. | this study was conducted to clarify the taxonomic status of francisella sp. strain ehime-1, a fish pathogen, in relation to the fish pathogens f. piscicida and f. philomiragia subsp. noatunensis and to f. philomiragia subsp. philomiragia. | 2009 | 19187160 |
| short report: time course of hematogenous dissemination of francisella tularensis a1, a2, and type b in laboratory mice. | tularemia is a tick-borne zoonotic bacterial disease. in the united states, human tularemia infections are caused by francisella tularensis subspecies tularensis (type a, clades a1 and a2) or f. tularensis subspecies holarctica (type b). we developed a mouse model that can be used to study the ability of ticks to acquire and transmit fully virulent strains of f. tularensis (a1, a2, and type b). we showed that 1) bacteremia was evident by 2 days post-infection (dpi) for a1, a2, and b, 2) bacterem ... | 2009 | 19190224 |
| evaluation of ultrafiltration cartridges for a water sampling apparatus. | to determine the efficiency of various ultrafiltration cartridges (ufc) in concentrating test micro-organisms from drinking water. | 2009 | 19191977 |
| a tularemia outbreak in an extended family in tokat province, turkey: observing the attack rate of tularemia. | we report the first tularemia epidemic occurring in tokat province, located in the middle black sea region of turkey, and some features of the cases. this epidemic has allowed the calculation of the attack rate of this disease because of its appearance in a single large family. | 2009 | 19195917 |
| phylogenomics and protein signatures elucidating the evolutionary relationships among the gammaproteobacteria. | the class gammaproteobacteria, which forms one of the largest groups within bacteria, is currently distinguished from other bacteria solely on the basis of its branching in phylogenetic trees. no molecular or biochemical characteristic is known that is unique to the class gammaproteobacteria or its different subgroups (orders). the relationship among different orders of gammaproteobacteria is also not clear. in this study, we present detailed phylogenomic and comparative genomic analyses on gamm ... | 2009 | 19196760 |
| a conserved alpha-helix essential for a type vi secretion-like system of francisella tularensis. | francisella tularensis harbors genes with similarity to genes encoding components of a type vi secretion system (t6ss) recently identified in several gram-negative bacteria. these genes include igla and iglb encoding igla and iglb, homologues of which are conserved in most t6sss. we used a yeast two-hybrid system to study the interaction of the igl proteins of f. tularensis lvs. we identified a region of igla, encompassing residues 33 to 132, necessary for efficient binding to iglb, as well as f ... | 2009 | 19201795 |
| the effect of open-air factors on the virulence and viability of airborne francisella tularensis. | unidentified open-air factors (oafs) found to be adverse to the survival of microorganisms suspended on microthreads were investigated for their effect on realistic aerosols of francisella tularensis in an open-air environment. this organism was chosen because it is probably the most infectious organism known to be capable of infecting both animals and man via the respiratory route, hence its potential use as a bioterrorist agent. a direct correlation was found between an open-air adverse effect ... | 2009 | 19203408 |
| francisella tularensis genes required for inhibition of the neutrophil respiratory burst and intramacrophage growth identified by random transposon mutagenesis of strain lvs. | francisella tularensis is a facultative intracellular pathogen and the causative agent of tularemia. we have shown that f. tularensis subspecies holarctica strain lvs prevents nadph oxidase assembly and activation in human neutrophils, but how this is achieved is unclear. herein, we used random transposon mutagenesis to identify lvs genes that affect neutrophil activation. our initial screen identified cara, carb, and pyrb, which encode the small and large subunits of carbamoylphosphate synthase ... | 2009 | 19204089 |
| nicotinamide mononucleotide synthetase is the key enzyme for an alternative route of nad biosynthesis in francisella tularensis. | enzymes involved in the last 2 steps of nicotinamide adenine dinucleotide (nad) cofactor biosynthesis, which catalyze the adenylylation of the nicotinic acid mononucleotide (namn) precursor to nicotinic acid dinucleotide (naad) followed by its amidation to nad, constitute promising drug targets for the development of new antibiotics. these enzymes, namn adenylyltransferase (gene nadd) and nad synthetase (gene nade), respectively, are indispensable and conserved in nearly all bacterial pathogens. ... | 2009 | 19204287 |
| inactivation of yersinia pseudotuberculosis 197 and francisella tularensis lvs in beverages by high pressure processing. | in 2003, the u.s. department of health and human services announced a new research program to develop technologies and strategies to prevent and minimize potential food safety and security threats. the threat of terrorist attacks against the nation's food supplies has created the need to study microorganisms not typically associated with foodborne illness. high-pressure processing has been proposed as a treatment to reduce yersinia pestis and francisella tularensis lvs levels in beverages. the o ... | 2009 | 19205479 |
| slow-onset inhibition of the fabi enoyl reductase from francisella tularensis: residence time and in vivo activity. | francisella tularensis is a highly virulent and contagious gram-negative intracellular bacterium that causes the disease tularemia in mammals. the high infectivity and the ability of the bacterium to survive for weeks in a cool, moist environment have raised the possibility that this organism could be exploited deliberately as a potential biological weapon. fatty acid biosynthesis (fas-ii) is essential for bacterial viability and has been validated as a target for the discovery of novel antibact ... | 2009 | 19206187 |
| a bayesian integration model of high-throughput proteomics and metabolomics data for improved early detection of microbial infections. | high-throughput (htp) technologies offer the capability to evaluate the genome, proteome, and metabolome of an organism at a global scale. this opens up new opportunities to define complex signatures of disease that involve signals from multiple types of biomolecules. however, integrating these data types is difficult due to the heterogeneity of the data. we present a bayesian approach to integration that uses posterior probabilities to assign class memberships to samples using individual and mu ... | 2009 | 19209722 |
| oral live vaccine strain-induced protective immunity against pulmonary francisella tularensis challenge is mediated by cd4+ t cells and antibodies, including immunoglobulin a. | francisella tularensis is an intracellular gram-negative bacterium and the etiological agent of pulmonary tularemia. given the high degrees of infectivity in the host and of dissemination of bacteria following respiratory infection, immunization strategies that target mucosal surfaces are critical for the development of effective vaccines against this organism. in this study, we have characterized the efficacy of protective immunity against pneumonic tularemia following oral vaccination with f. ... | 2009 | 19211773 |
| an approach to the identification of t cell epitopes in the genomic era: application to francisella tularensis. | the identification and characterization of epitopes is essential for modern immunologic studies. here, we describe a novel methodology we have developed to identify t cell epitopes exploiting the phenomenon of cross presentation. particulate antigens, in the form of beads, are very effective in delivering exogenous antigen to both the class i and class ii pathways. we will review our efforts to screen entire genomes of pathogens for t cell epitopes taking advantage of the advances in genomics us ... | 2009 | 19212707 |
| intracellular fate of francisella tularensis within arthropod-derived cells. | since transmission of francisella tularensis into the mammalian host occurs via arthropod vectors such as ticks, mosquitoes, horseflies and deerflies, recent studies have established drosophila melanogaster as an arthropod vector model system. nothing is known about the intracellular fate of f. tularensis within arthropod-derived cells, and the role of this host-parasite adaptation in the evolution of this pathogen to infect mammals. in this report, we explored intracellular trafficking of f. tu ... | 2009 | 19220402 |
| hfq, a novel pleiotropic regulator of virulence-associated genes in francisella tularensis. | francisella tularensis is a highly infectious pathogen that infects animals and humans, causing tularemia. the ability to replicate within macrophages is central for virulence and relies on expression of genes located in the francisella pathogenicity island (fpi), as well as expression of other genes. regulation of fpi-encoded virulence gene expression in f. tularensis involves at least four regulatory proteins and is not fully understood. here we studied the rna-binding protein hfq in f. tulare ... | 2009 | 19223477 |
| 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 ... | 2009 | 19232853 |
| identification of a dominant cd4 t cell epitope in the membrane lipoprotein tul4 from francisella tularensis lvs. | francisella tularensis is a gram-negative intracellular bacterium that is the causative agent of tularemia. small mammals such as rodents and rabbits, as well as some biting arthropods, serve as the main vectors for environmental reservoirs of f. tularensis. the low infectious dose, ability to aerosolize the organism, and the possibility of generating antibiotic resistant strains make f. tularensis a prime organism for use in bioterrorism. as a result, some strains of f. tularensis have been pla ... | 2009 | 19233475 |
| t cells from lungs and livers of francisella tularensis-immune mice control the growth of intracellular bacteria. | parenteral and respiratory vaccinations with the intracellular bacterium francisella tularensis have been studied using the live vaccine strain (lvs) in a mouse model, and spleen cells from immune mice are often used for immunological studies. however, mechanisms of host immunological responses may be different in nonlymphoid organs that are important sites of infection, such as lung and liver. using parenteral (intradermal) or respiratory (cloud aerosol) vaccination, here we examine the functio ... | 2009 | 19237526 |
| francisella tularensis phagosomal escape does not require acidification of the phagosome. | following uptake, francisella tularensis enters a phagosome that acquires limited amounts of lysosome-associated membrane glycoproteins and does not acquire cathepsin d or markers of secondary lysosomes. with additional time after uptake, f. tularensis disrupts its phagosomal membrane and escapes into the cytoplasm. to assess the role of phagosome acidification in phagosome escape, we followed acidification using the vital stain lysotracker red and acquisition of the proton vacuolar atpase (vatp ... | 2009 | 19237528 |
| molecular epidemiology of francisella tularensis in the united states. | in the united states, tularemia is caused by francisella tularensis subsps. tularensis (type a) and holarctica (type b). molecular subtyping has further divided type a into 2 subpopulations, a1 and a2. significant mortality differences were previously identified between human infections caused by a1 (14%), a2 (0%) and type b (7%). to verify these findings and to further define differences among genotypes, we performed a large-scale molecular epidemiologic analysis of f. tularensis isolates from ... | 2009 | 19245342 |
| nonrandom distribution of vector ticks (dermacentor variabilis) infected by francisella tularensis. | the island of martha's vineyard, massachusetts, is the site of a sustained outbreak of tularemia due to francisella tularensis tularensis. dog ticks, dermacentor variabilis, appear to be critical in the perpetuation of the agent there. tularemia has long been characterized as an agent of natural focality, stably persisting in characteristic sites of transmission, but this suggestion has never been rigorously tested. accordingly, we sought to identify a natural focus of transmission of the agent ... | 2009 | 19247435 |
| the impact of chemokine receptor cx3cr1 deficiency during respiratory infections with mycobacterium tuberculosis or francisella tularensis. | recruitment of immune cells to infection sites is a critical component of the host response to pathogens. this process is facilitated partly through interactions of chemokines with cognate receptors. here, we examine the importance of fractalkine (cx3cl1) receptor, cx3cr1, which regulates function and trafficking of macrophages and dendritic cells, in the host's ability to control respiratory infections with mycobacterium tuberculosis or francisella tularensis. following low-dose aerosol challen ... | 2009 | 19250281 |
| tularaemia of middle ear with suppurative lymphadenopathy and retropharyngeal abscess. | we report an extremely rare case of otitis media due to francisella tularensis, complicated by multiple suppurative cervical lesions and a lasting conductive hearing loss. | 2009 | 19250590 |
| antigen-specific b-1a antibodies induced by francisella tularensis lps provide long-term protection against f. tularensis lvs challenge. | francisella tularensis (ft), a gram-negative intracellular bacterium, is the etiologic agent of tularemia. infection of mice with <10 ft live vaccine strain (ft lvs) organisms i.p. causes a lethal infection that resembles human tularemia. here, we show that immunization with as little as 0.1 ng ft lvs lipopolysaccharide (ft-lps), but not ft lipid a, generates a rapid antibody response that protects wild-type (wt) mice against lethal ft lvs challenge. protection is not induced in ft-lps-immunized ... | 2009 | 19251656 |
| 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 ... | 2009 | 19251856 |
| expression, purification and crystallization of class c acid phosphatases from francisella tularensis and pasteurella multocida. | class c nonspecific acid phosphatases are bacterial enzymes that are secreted across the cytoplasmic membrane and hydrolyze a variety of phosphomonoesters at acidic ph. these enzymes are of interest for the development of improved vaccines and clinical diagnostic methods. in one case, the category a pathogen francisella tularensis, the class c phosphatase plays a role in bacterial fitness. here, the cloning, expression, purification and crystallization methods for the class c acid phosphatases f ... | 2009 | 19255471 |
| 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 ... | 2009 | 20224751 |
| 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. | 2009 | 20073421 |
| 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 ... | 2009 | 19923904 |
| 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 ... | 2009 | 20190973 |
| [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. | 2009 | 20137470 |
| [participation of murine rodents in circulation of agents of tularemia and hemorrhagic fever in kola peninsula]. | results of virological and bacteriological studies of wild mammals of 11 species from rodentia and cricetidae genuses during epizootic period (spring-autumn 2006-2007) in murmansk region are presented. the number of red-baked mice (clethrionomys) and common vole (microtus) was rising. antigen of hemorrhagic fever with renal syndrome virus as well as tularemia pathogen were found in background rodent species. | 2008 | 19004288 |
| inhibition of expression in escherichia coli of a virulence regulator mglb of francisella tularensis using external guide sequence technology. | external guide sequences (egss) have successfully been used to inhibit expression of target genes at the post-transcriptional level in both prokaryotes and eukaryotes. we previously reported that egs accessible and cleavable sites in the target rnas can rapidly be identified by screening random egs (regs) libraries. here the method of screening regs libraries and a partial rnase t1 digestion assay were used to identify sites accessible to egss in the mrna of a global virulence regulator mglb fro ... | 2008 | 19005569 |
| re-emergence of tularemia in germany: presence of francisella tularensis in different rodent species in endemic areas. | tularemia re-emerged in germany starting in 2004 (with 39 human cases from 2004 to 2007) after over 40 years of only sporadic human infections. the reasons for this rise in case numbers are unknown as is the possible reservoir of the etiologic agent francisella (f.) tularensis. no systematic study on the reservoir situation of f. tularensis has been published for germany so far. | 2008 | 19014635 |
| re-assembly of the genome of francisella tularensis subsp. holarctica osu18. | francisella tularensis is a highly infectious human intracellular pathogen that is the causative agent of tularemia. it occurs in several major subtypes, including the live vaccine strain holarctica (type b). f. tularensis is classified as category a biodefense agent in part because a relatively small number of organisms can cause severe illness. three complete genomes of subspecies holarctica have been sequenced and deposited in public archives, of which osu18 was the first and the only strain ... | 2008 | 18927608 |
| nk cells and gamma interferon coordinate the formation and function of hepatic granulomas in mice infected with the francisella tularensis live vaccine strain. | host innate immune responses to many intracellular pathogens include the formation of inflammatory granulomas that are thought to provide a physical barrier between the microbe and host. because two common features of infections with the live vaccine strain (lvs) of francisella tularensis within the mouse liver are the formation of granulomas and the production of gamma interferon (ifn-gamma), we have asked what role ifn-gamma plays in hepatic granuloma formation and function. francisella antige ... | 2008 | 18227174 |
| the acrab rnd efflux system from the live vaccine strain of francisella tularensis is a multiple drug efflux system that is required for virulence in mice. | the ability of bacterial pathogens to infect and cause disease is dependent upon their ability to resist antimicrobial components produced by their host, such as bile acids, fatty acids and other detergent-like molecules, and products of the innate immune system (e.g. cationic antimicrobial peptides). bacterial resistance to the antimicrobial effects of such compounds is often mediated by active efflux systems belonging to the resistance-nodulation-division (rnd) family of transporters. rnd effl ... | 2008 | 18179581 |
| a functional genomic yeast screen to identify pathogenic bacterial proteins. | many bacterial pathogens promote infection and cause disease by directly injecting into host cells proteins that manipulate eukaryotic cellular processes. identification of these translocated proteins is essential to understanding pathogenesis. yet, their identification remains limited. this, in part, is due to their general sequence uniqueness, which confounds homology-based identification by comparative genomic methods. in addition, their absence often does not result in phenotypes in virulenc ... | 2008 | 18208325 |
| an intracellularly inducible gene involved in virulence and polyphosphate production in francisella. | francisella tularensis is an intracellular pathogen capable of multiplying to high levels in macrophages. by protein analysis, only a few proteins have been shown previously to be expressed at high levels in macrophages relative to bacteria grown in culture media. to identify additional genes that show increased expression during intracellular growth, we developed a plasmid for use in francisella based on the induction of expression of green fluorescent protein. clones of f. tularensis subsp. no ... | 2008 | 18809544 |
| tularemia in children. | tularemia, an infection caused by the coccobacilus francisella tularensis, can be a difficult disease process to diagnose and treat. the aim of this study was to evaluate an epidemic of tularemia in bursa. | 2008 | 18810348 |
| effective host response to francisella tularensis requires functional mast cells. | evaluation of: ketavarapu jm, rodriguez ar, yu j et al.: mast cells inhibit intramacrophage francisella tularensis replication via contact and secreted products including il-4. proc. natl acad. sci. usa 105(27), 9313-9318 (2008). the intracellular pathogen francisella tularensis is a highly infectious organism that infects cells of the immune system. mast cells have been known for their role in anaphylaxis, although they are also important for their ability to aid in the defense against pathogen ... | 2008 | 18811234 |
| [interaction of s- and r-lipopolysaccharides of francisella tularensis with lypopolysaccharide-binding protein of human serum]. | investigation of ability of francisella tularensis s- and r-lypopolysaccharide (lps) preparations as well as the live bacteria with different chemotypes to interact with human lypopolysaccharide-binding protein (lbp) was carried out. it was found that lps preparations derived from virulent(s-lps) or isogenic avirulent mutant (r-lps) strains of f. tularensis had markedly lower affinity to lbp as compared with typical s-lps of salmonella abortus and r-lps of yersinia pestis. it was shown that r-lp ... | 2008 | 18819401 |
| [temperate legionella bacteriophage: discovery and characteristics]. | for the first time, temperate legionella bacteriophage was isolated from organs of guinea pig infected with philadelphia 1 strain of legionella pneumophila. negative colonies of bactriophage from 1.5 to 2.5 mm in diameter were detected. central part of them was transparent and surrounded by peripheral zone of partial lysis. electron microscopy showed that corpuscles of the phage consist from multifaceted elongated head of stretched hexagonal form and short tail. the bacteriophage lyzed bacteria, ... | 2008 | 18819413 |
| evasion of complement-mediated lysis and complement c3 deposition are regulated by francisella tularensis lipopolysaccharide o antigen. | the bacterium francisella tularensis (ft) is a potential weapon of bioterrorism when aerosolized. macrophage infection is necessary for disease progression and efficient phagocytosis by human macrophages requires serum opsonization by complement. microbial complement activation leads to surface deposition of a highly regulated protein complex resulting in opsonization or membrane lysis. the nature of complement component c3 deposition, i.e., c3b (opsonization and lysis) or c3bi (opsonization onl ... | 2008 | 18832715 |
| genetic dissection of the francisella novicida restriction barrier. | francisella tularensis is the causative agent of tularemia and is a category a select agent. francisella novicida, considered by some to be one of four subspecies of f. tularensis, is used as a model in pathogenesis studies because it causes a disease similar to tularemia in rodents but is not harmful to humans. f. novicida exhibits a strong restriction barrier which reduces the transformation frequency of foreign dna up to 10(6)-fold. to identify the genetic basis of this barrier, we carried ou ... | 2008 | 18835994 |
| humoral and cell-mediated immunity to the intracellular pathogen francisella tularensis. | summary: francisella tularensis can cause fatal respiratory tularemia in humans and animals and is increasingly being isolated in the united states and several european countries. the correlates of protective immunity against this intracellular bacterium are not known, and currently there are no licensed vaccines available for human use. cell-mediated immunity has long been believed to be critical for protection, and the importance of humoral immunity is also now recognized. furthermore, synergy ... | 2008 | 18837786 |
| global transcriptional response to mammalian temperature provides new insight into francisella tularensis pathogenesis. | after infecting a mammalian host, the facultative intracellular bacterium, francisella tularensis, encounters an elevated environmental temperature. we hypothesized that this temperature change may regulate genes essential for infection. | 2008 | 18842136 |
| development and application of the active surveillance of pathogens microarray to monitor bacterial gene flux. | human and animal health is constantly under threat by emerging pathogens that have recently acquired genetic determinants that enhance their survival, transmissibility and virulence. we describe the construction and development of an active surveillance of pathogens (asp) oligonucleotide microarray, designed to 'actively survey' the genome of a given bacterial pathogen for virulence-associated genes. | 2008 | 18844996 |
| the early phagosomal stage of francisella tularensis determines optimal phagosomal escape and francisella pathogenicity island protein expression. | francisella tularensis is an intracellular pathogen that can survive and replicate within macrophages. following phagocytosis and transient interactions with the endocytic pathway, f. tularensis rapidly escapes from its original phagosome into the macrophage cytoplasm, where it eventually replicates. to examine the importance of the nascent phagosome for the francisella intracellular cycle, we have characterized early trafficking events of the f. tularensis subsp. tularensis strain schu s4 in a ... | 2008 | 18852245 |
| infected-host-cell repertoire and cellular response in the lung following inhalation of francisella tularensis schu s4, lvs, or u112. | francisella tularensis causes systemic disease in humans and other mammals, with high morbidity and mortality associated with inhalation-acquired infection. f. tularensis is a facultative intracellular pathogen, but the scope and significance of cell types infected during disease is unknown. using flow cytometry, we identified and quantified infected-cell types and assessed the impact of infection on cell populations following inhalation of f. tularensis strains u112, lvs, and schu s4. initially ... | 2008 | 18852251 |
| persistence of category a select agents in the environment. | 2008 | 18065629 | |
| detection of alpha and gamma-proteobacteria in amblyomma triste (acari: ixodidae) from uruguay. | amblyomma triste is the most prevalent tick species reported in human tick bites in uruguay and has been found to be infected with rickettsia parkeri, but no other microorganisms have been reported from this tick. a sample of 254 adults of a. triste was collected by flagging on vegetation in suburban areas in southern uruguay. pools of five ticks were assembled and a screening for the dna from the resulting 51 pools was realized by pcr assays using primers for amplifying a fragment of 16s rrna g ... | 2008 | 18071910 |
| identification of francisella tularensis lipoproteins that stimulate the toll-like receptor (tlr) 2/tlr1 heterodimer. | the innate immune response to francisella tularensis is primarily mediated by tlr2, though the bacterial products that stimulate this receptor remain unknown. here we report the identification of two francisella lipoproteins, tul4 and ftt1103, which activate tlr2. we demonstrate that tul4 and ftt1103 stimulate chemokine production in human and mouse cells in a tlr2-dependent way. using an assay that relies on chimeric tlr proteins, we show that tul4 and ftt1103 stimulate exclusively the tlr2/tlr ... | 2008 | 18079113 |
| the presence of infectious extracellular francisella tularensis subsp. novicida in murine plasma after pulmonary challenge. | 2008 | 18087734 | |
| genetic elements for selection, deletion mutagenesis and complementation in francisella spp. | francisella novicida is a gram-negative pathogen that can induce disease in mice that mimics human tularemia, and is nearly identical to francisella tularensis at the genomic level. in this work a number of antibiotic marker cassettes that incorporate a strong f. novicida promoter is constructed, which greatly enhances selection in f. novicida and f. tularensis. two low-copy plasmid vectors based on a broad-host-range plasmid, and an integrating vector have also been made, and these can be used ... | 2008 | 18021237 |
| discrimination between biothreat agents and 'near neighbor' species using a resequencing array. | timely identification of biothreat organisms from large numbers of clinical or environmental samples in potential outbreak or attack scenario is critical for effective diagnosis and treatment. this study aims to evaluate the potential of resequencing arrays for this purpose. albeit suboptimal, this report demonstrated that respiratory pathogen microarray version 1 can identify bacillus anthracis, francisella tularensis, yersinia pestis and distinguish them from benign 'near neighbor' species in ... | 2008 | 19049648 |
| francisella genes required for replication in mosquito cells. | francisella tularensis, a potential bioterrorism agent, is transmitted by arthropod vectors and causes tularemia in many mammals, including humans. francisella novicida causes disease with similar pathology in mice. we show that f. novicida invades hemocyte-like cells of the sualb cell line derived from anopheles gambiae and replicates vigorously within these cells. we used transposon knockouts of single genes of f. novicida to show that bacterial growth within these insect cells is dependent on ... | 2008 | 19058636 |
| levofloxacin rescues mice from lethal intra-nasal infections with virulent francisella tularensis and induces immunity and production of protective antibody. | the ability to protect mice against respiratory infections with virulent francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. in this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with f. tularensis schu s4. we show that mice infected with a lethal dose of schu s4, via an intra-nasal challenge, could be protected with levoflo ... | 2008 | 18930100 |