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eschar and neck lymphadenopathy caused by francisella tularensis after a tick bite: a case report. 201121418587
sensitivity of francisella tularensis to ultrapure water and deoxycholate: implications for bacterial intracellular growth assay in macrophages.the ability of francisella tularensis to replicate in macrophages is critical for its pathogenesis, therefore intracellular growth assays are important tools for assessing virulence. we show that two lysis solutions commonly used in these assays, deionized water and deoxycholate in pbs, lead to highly inaccurate measurements of intracellular bacterial survival.201121420447
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
features of sepsis caused by pulmonary infection with francisella tularensis type a strain.the virulence mechanisms of francisella tularensis, the causative agent of severe pneumonia in humans and a cdc category a bioterrorism agent, are not fully defined. as sepsis is the leading cause of mortality associated with respiratory infections, we determined whether, in the absence of any known bacterial toxins, a deregulated host response resulting in sepsis syndrome is associated with lethality of respiratory infection with the virulent human type a strain schus4 of f. tularensis. the c57 ...201121440052
persistence of cell-mediated immunity three decades after vaccination with the live vaccine strain of francisella tularensis.the efficacy of many vaccines against intracellular bacteria depends on the generation of cell-mediated immunity, but studies to determine the duration of immunity are usually confounded by re-exposure. the causative agent of tularemia, francisella tularensis, is rare in most areas and, therefore, tularemia vaccination is an interesting model for studies of the longevity of vaccine-induced cell-mediated immunity. here, lymphocyte proliferation and cytokine production in response to f. tularensis ...201121442618
measurement of macrophage-mediated killing of intracellular bacteria, including francisella and mycobacteria.macrophages activated by t cell cytokines are a critical defense mechanism against intracellular bacterial pathogens. this unit presents two general methods for assessing the capacity of mouse macrophages, activated with either soluble cytokines or whole immune t lymphocytes, to control or reduce numbers of intracellular bacteria residing within them. "measurement of killing" is inferred from a reduction in the number of colony-forming units (cfu) of bacteria at the end of a culture period, comp ...201121462167
infection of mice with francisella as an immunological model.this unit describes the utility of various mouse models of infection for studying pathogenesis and adaptive immune responses to the facultative intracellular bacteria pathogen francisella tularensis. by judicious use of different combinations of mouse and bacterial strains, as well as different routes of infection, murine tularemia models may be used to explore a complete picture of f. tularensis infection and immunity. moreover, studies using francisella, particularly the live vaccine strain (l ...201121462168
tryptophan prototrophy contributes to francisella tularensis evasion of gamma interferon-mediated host defense.francisella tularensis is able to survive and replicate within host macrophages, a trait that is associated with the high virulence of this bacterium. the trpab genes encode the enzymes required for the final two steps in tryptophan biosynthesis, with trpb being responsible for the conversion of indole to tryptophan. consistent with this function, an f. tularensis subsp. novicida trpb mutant is unable to grow in defined medium in the absence of tryptophan. the trpb mutant is also attenuated for ...201121464086
characterization of monoclonal antibodies to terminal and internal o-antigen epitopes of francisella tularensis lipopolysaccharide.the lipopolysaccharide (lps) of francisella tularensis (ft), the gram negative bacterium that causes tularemia, has been shown to be a main protective antigen in mice and humans; we have previously demonstrated that murine anti-ft lps igg2a monoclonal antibodies (mabs) can protect mice against otherwise lethal intranasal infection with the ft live vaccine strain (lvs). here we show that four igg2a anti-lps mabs are specific for the o-polysaccharide (o-antigen [oag]) of ft lps. but whereas three ...201121466282
a myd88-dependent ifn?r-ccr2 signaling circuit is required for mobilization of monocytes and host defense against systemic bacterial challenge.monocytes are mobilized to sites of infection via interaction between the chemokine mcp-1 and its receptor, ccr2, at which point they differentiate into macrophages that mediate potent antimicrobial effects. in this study, we investigated the mechanisms by which monocytes are mobilized in response to systemic challenge with the intracellular bacterium francisella tularensis. we found that mice deficient in myd88, interferon-? (ifn?)r or ccr2 all had defects in the expansion of splenic monocyte p ...201121467996
automated lipid a structure assignment from hierarchical tandem mass spectrometry data.infusion-based electrospray ionization (esi) coupled to multiple-stage tandem mass spectrometry (ms(n)) is a standard methodology for investigating lipid a structural diversity (shaffer et al. j. am. soc. mass. spectrom. 18(6), 1080-1092, 2007). annotation of these ms(n) spectra, however, has remained a manual, expert-driven process. in order to keep up with the data acquisition rates of modern instruments, we devised a computational method to annotate lipid a ms(n) spectra rapidly and automatic ...201121472520
[epidemiological evaluation of a rapidly-prevented tularemia outbreak in canakkale province, turkey].tularemia is a disease caused by francisella tularensis and widely seen at northern hemisphere of the world. in turkey, oropharyngeal infections caused by a less virulent serotype f.tularensis subsp. holarctica are more prevalent. the aim of this study was to present the results of an epidemiological research performed after the detection of tularemia cases from biga county of canakkale province, turkey, in december 2009. following the report of two tularemia suspected cases from two villages (b ...201121341159
[evaluation of the oropharyngeal tularemia cases admitted to our hospital from the provinces of central anatolia].tularemia caused by the bacterium francisella tularensis is a zoonotic infection which has re-emerged in turkey in recent years as water-borne endemics. oropharyngeal form is the most frequently reported form of the disease from turkey. the aim of this study was to evaluate the clinical and laboratory findings of oropharyngeal tularemia patients admitted to ear, nose & throat outpatient clinic between january-march 2010. a total of 10 patients (age range: 16-80 years, mean age: 43.9 years; nine ...201121341160
[tularemia seroprevalence in the risky population living in both rural and urban areas of erzurum].tularemia which is a zoonotic infection, caused by francisella tularensis, has become a re-emerging disease in turkey. infection is often transmitted to human by handling animal tissues and products, but it is also possible to acquire the disease from contaminated water or food. recently several cases and epidemics of tularemia have been reported in the northwest areas of turkey, particularly in marmara and west black sea regions. erzurum is a city in eastern anatolia region, turkey and animal h ...201121341161
francisella infections in farmed and wild aquatic organisms.abstract: over the last 10 years or so, infections caused by bacteria belonging to a particular branch of the genus francisella have become increasingly recognised in farmed fish and molluscs worldwide. while the increasing incidence of diagnoses may in part be due to the development and widespread availability of molecular detection techniques, the domestication of new organisms has undoubtedly instigated emergence of clinical disease in some species. francisellosis in fish develops in a simila ...201121385413
identification of a putative chaperone involved in stress resistance and virulence in francisella tularensis.francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. this facultative intracellular bacterium replicates in vivo mainly inside macrophages and therefore has developed strategies to resist this stressful environment. here, we identified a novel genetic locus that is important for stress resistance and intracellular survival of f. tularensis. in silico and transcriptional analyses suggest that this locus (genes ftl_0200 to ftl_0209 in the live vaccine str ...201121245269
a high-throughput fluorescence polarization assay for inhibitors of gyrase b.dna gyrase, a type ii topoisomerase that introduces negative supercoils into dna, is a validated antibacterial drug target. the holoenzyme is composed of 2 subunits, gyrase a (gyra) and gyrase b (gyrb), which form a functional a(2)b(2) heterotetramer required for bacterial viability. a novel fluorescence polarization (fp) assay has been developed and optimized to detect inhibitors that bind to the adenosine triphosphate (atp) binding domain of gyrb. guided by the crystal structure of the natural ...201121245469
francisella infections in fish and shellfish.a series of recent reports have implicated bacteria from the family francisellaceae as the cause of disease in farmed and wild fish and shellfish species such as atlantic cod, gadus morhua l., tilapia, oreochromis spp., atlantic salmon, salmo salar l., three-line grunt, parapristipoma trilineatum (thunberg), ornamental cichlid species, hybrid striped bass morone chrysops x m. saxatilis and, recently, a shellfish species, the giant abalone, haliotisgigantea gmelin. the range of taxa affected will ...201121306585
genetic manipulation of francisella tularensis.francisella tularensis is a facultative intracellular pathogen that causes the disease tularemia. f. tularensis subsp. tularensis causes the most severe disease in humans and has been classified as a category a select agent and potential bioweapon. there is currently no vaccine approved for human use, making genetic manipulation of this organism critical to unraveling the genetic basis of pathogenesis and developing countermeasures against tularemia. the development of genetic techniques applica ...201121607086
chlorine dioxide inactivation of bacterial threat agents.aims:  to evaluate the efficacy of chlorine dioxide (clo(2) ) against seven species of bacterial threat (bt) agents in water. methods and results:  two strains of bacillus anthracis spores, yersinia pestis, francisella tularensis, burkholderia pseudomallei, burkholderia mallei, and brucella species were each inoculated into a clo(2) solution with an initial concentration of 2·0 mg l(-1) (spores only) and 0·25 mg l(-1) (all other bacteria) at ph 7 or 8, 5°c or 25°c. at 0·25 mg l(-1) in potable wa ...201121623848
whole-genome immunoinformatic analysis of f. tularensis: predicted ctl epitopes clustered in hotspots are prone to elicit a t-cell response.the cellular arm of the immune response plays a central role in the defense against intracellular pathogens, such as f. tularensis. to date, whole genome immunoinformatic analyses were limited either to relatively small genomes (e.g. viral) or to preselected subsets of proteins in complex pathogens. here we present, for the first time, an unbiased bacterial global immunoinformatic screen of the 1740 proteins of f. tularensis subs. holarctica (lvs), aiming at identification of immunogenic peptide ...201121625462
francisella tularensis: a red-blooded pathogen. 201121628652
invasion of erythrocytes by francisella tularensis.(see the editorial commentary by conlan, on pages 6-8.) francisella tularensis is the causative agent of tularemia and is classified as a category a biodefense agent by the centers for disease control and prevention because of its highly infectious nature. f. tularensis infects leukocytes and exhibits an extracellular phase in the blood of the host. it is unknown, however, whether f. tularensis can infect erythrocytes; thus, we examined this possibility in vivo and in vitro. in the murine model ...201121628658
salmonella synthesizing 1-monophosphorylated lipopolysaccharide exhibits low endotoxic activity while retaining its immunogenicity.the development of safe live, attenuated salmonella vaccines may be facilitated by detoxification of its lps. recent characterization of the lipid a 1-phosphatase, lpxe, from francisella tularensis allowed us to construct recombinant, plasmid-free strains of salmonella that produce predominantly 1-dephosphorylated lipid a, similar to the adjuvant approved for human use. complete lipid a 1-dephosphorylation was also confirmed under low ph, low mg(2+) culture conditions, which induce lipid a modif ...201121632711
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
[a water-borne tularemia outbreak caused by francisella tularensis subspecies halorctica in central anatolia region.]in this study, we investigated a waterborne tularemia outbreak occured in kadiozu, a village of cerkes county of cankiri province (located in north-west part of central anatolia, turkey) between 18 november 2009-24 december 2009. active surveillance was conducted to determine clinical characteristics and risk factors of cases after two patients from the same village had been diagnosed as oropharyngeal tularemia. all villagers were examined, and clinical specimens from cases and water samples whi ...201121644066
francisella noatunensis in atlantic cod (gadus morhua l.); waterborne transmission and immune responses.this is the first report that confirms horizontal waterborne transmission of francisellosis in atlantic cod. to investigate the transmission of disease, particle reduced water was transferred from a tank with intraperitoneally infected cod to a tank with healthy cod. waterborne transmission of francisella noatunensis was confirmed in the effluent group using immunohistochemistry and real-time quantitative pcr (rt-qpcr). the bacteria were located inside the accumulated macrophage-like cells. spec ...201121645622
diversity and coexistence of tick-borne pathogens in central germany.in total, 1000 ixodes ricinus l. ticks were collected from a small recreational forest area in central germany (thuringia) and investigated for the presence of borrelia spp., babesia spp., anaplasma spp., rickettsia spp., coxiella burnetii, and francisella tularensis. overall, 43.6% of the ticks were infected with at least one pathogen. in 8.4% of ticks double infections were detected, and 1.6% harbored more than two pathogens. in this study, we present data on the coexistence of established and ...201121661327
common ancestry and novel genetic traits of francisella novicida-like isolates from north america and australia as revealed by comparative genomic analyses.francisella novicida is a close relative of francisella tularensis, the causative agent of tularemia. the genomes of f. novicida-like clinical isolates 3523 (australian strain) and fx1 (texas strain) were sequenced and compared to f. novicida strain u112 and f. tularensis strain schu s4. the strain 3523 chromosome is 1,945,310 bp and contains 1,854 protein-coding genes. the strain fx1 chromosome is 1,913,619 bp and contains 1,819 protein-coding genes. nucmer analyses revealed that the genomes of ...201121666011
francisella tularensis lvs-induced interleukin-12 p40 cytokine production mediates dendritic cell migration through il-12 receptor ╬▓1.three cytokines use the il-12p40 cytokine subunit namely: il-12p70 (il-12-comprised of il-12p40 and il-12p35), il-23 (comprised of the il-12p40 and il-23p19 subunits) and homodimeric il-12p40 (il-12(p40)(2)). following activation, immature dendritic cells (dcs) upregulate the chemokine receptor chemokine-c-receptor 7 (ccr7), and migrate in response to homeostatic chemokines such as chemokine (c-c motif) ligand 19 (ccl19). induction of the cytokine il-12p40 in response to pathogen-exposure, likel ...201121669537
a francisella tularensis locus required for spermine responsiveness is necessary for virulence.tularemia is a debilitating febrile illness caused by the category a biodefense agent francisella tularensis. this pathogen infects over 250 different hosts, has a low infectious dose, and causes high morbidity and mortality. our understanding of the mechanisms by which f. tularensis senses and adapts to host environments is incomplete. polyamines, including spermine, regulate the interactions of f. tularensis with host cells. however, it is not known whether responsiveness to polyamines is nece ...201121670171
mpys is required for ifn response factor 3 activation and type i ifn production in the response of cultured phagocytes to bacterial second messengers cyclic-di-amp and cyclic-di-gmp.cyclic-di-gmp and cyclic-di-amp are second messengers produced by bacteria and influence bacterial cell survival, differentiation, colonization, biofilm formation, virulence, and bacteria-host interactions. in this study, we show that in both raw264.7 macrophage cells and primary bone marrow-derived macrophages, the production of ifn-β and il-6, but not tnf, in response to cyclic-di-amp and cyclic-di-gmp requires mpys (also known as sting, mita, and tmem173). furthermore, expression of mpys was ...201121813776
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
the use of acid treatment and a selective medium to enhance the recovery of francisella tularensis from water.francisella tularensis has been associated with naturally occurring waterborne outbreaks and is also of interest as a potential biological weapon. recovery of this pathogen from water using cultural methods is challenging due to the organism's fastidious growth requirements and interference by indigenous bacteria. a fifteen minute acid treatment procedure prior to culture on a selective agar was evaluated for recovery of f. tularensis from seeded water samples. mean levels of reduction of virule ...201121803910
identification of francisella tularensis outer membrane protein a (fopa) as a protective antigen for tularemia.francisella tularensis is a highly pathogenic gram negative bacterium that infects multiple sites in a host, including the skin and the respiratory tract, which can lead to the onset of a deadly disease with a 50% mortality rate. the live vaccine strain (lvs) of f. tularensis, while attenuated in humans but still virulent in mice, is not an option for vaccine use in the united states due to safety concerns, and currently no fda approved vaccine exists. the purpose of the present work was to asse ...201121803089
host-adaptation of francisella tularensis alters the bacterium's surface-carbohydrates to hinder effectors of innate and adaptive immunity.the gram-negative bacterium francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. the presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. previously we reported in vitro culture conditions for this bacterium which, in contr ...201121799828
francisella noatunensis subsp. noatunensis is the aetiological agent of visceral granulomatosis in wild atlantic cod gadus morhua.during the 1980s and 1990s wild-caught cod displaying visceral granulomatosis were sporadically identified from the southern north sea. presumptive diagnoses at the time included mycobacterial infection, although mycobacteria were never cultivated or observed histologically from these fish. farmed cod in norway displaying gross pathology similar to that identified previously in cod from the southern north sea were recently discovered to be infected with the bacterium francisella noatunensis subs ...201121797037
outbreak of tularaemia in brown hares (lepus europaeus) in france, january to march 2011. 201121794224
large scale comparison of innate responses to viral and bacterial pathogens in mouse and macaque.viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. to determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (pr8 and fuj/02 influenza a) and two bacterial (mycobacteriu ...201121789257
genetic relationship between francisella tularensis strains from china and from other countries.to study the types of subspecies of francisella tularensis from china and to investigate the genetic relationships between f. tularensis strains from china and from other countries.201121784318
quaternary structure, conformational variability, and global motions of phosphoglucosamine mutase.phosphoglucosamine mutase (pngm) is a bacterial enzyme that participates in the peptidoglycan biosynthetic pathway. recent crystal structures of pngm from two bacterial pathogens, bacillus anthracis and francisella tularensis, revealed key structural features of this enzyme for the first time. here, we follow up on several novel findings from the crystallographic studies, including the observation of a structurally conserved interface between polypeptide chains and conformational variability of ...201121767345
ifn-{beta} mediates suppression of il-12p40 in human dendritic cells following infection with virulent francisella tularensis.active suppression of inflammation is a strategy used by many viral and bacterial pathogens, including virulent strains of the bacterium francisella tularensis, to enable colonization and infection in susceptible hosts. in this study, we demonstrated that virulent f. tularensis strain schus4 selectively inhibits production of il-12p40 in primary human cells via induction of ifn-ß. in contrast to the attenuated live vaccine strain, infection of human dendritic cells with virulent schus4 failed to ...201121753150
role of tlr signaling in francisella tularensis-lps-induced, antibody-mediated protection against francisella tularensis challenge.immunization with ft-lps provokes an antigen-specific, b-1a cell-derived antibody response that protects wt mice against an otherwise lethal challenge with ft lvs. however, this same regimen offers limited protection to tlr2(-/-) mice, despite production of wt levels of anti-ft-lps antibodies. as ft-lps exhibits no tlr2 agonist activity, and macrophage-induced cytokine production in response to ft lvs is overwhelmingly tlr2-dependent, we hypothesized that treatment of tlr2(-/-) mice with an alte ...201121750122
the capbca locus is required for intracellular growth of francisella tularensis lvs.francisella tularensis is the causative agent of tularemia and a category a bioterrorism agent. the molecular basis for the extreme virulence of f. tularensis remains unclear. our recent study found that capbca, three neighboring genes, are necessary for the infection of f. tularensis live vaccine strain (lvs) in a respiratory infection mouse model. we here show that the capbca genes are necessary for in vivo growth of f. tularensis lvs in the lungs, spleens, and livers of balb/c mice. unmarked ...201121747799
intra-vacuolar proliferation of f. novicida within h. vermiformis.francisella tularensis is a gram negative facultative intracellular bacterium that causes the zoonotic disease tularemia. free-living amebae, such as acanthamoeba and hartmannella, are environmental hosts of several intracellular pathogens. epidemiology of f. tularensis in various parts of the world is associated with water-borne transmission, which includes mosquitoes and amebae as the potential host reservoirs of the bacteria in water resources. in vitro studies showed intracellular replicatio ...201121747796
francisella recognition by inflammasomes: differences between mice and men.pathogen recognition by intracellular sensors involves the assembly of a caspase-1 activation machine termed the inflammasome. intracellular pathogens like francisella that gain access to the cytosolic detection systems are useful tools to uncover the details of caspase-1 activation events. this review overviews francisella function in the mononuclear phagocyte with particular attention to inflammasome versus pyroptosome roles and outlines differences between mouse and human caspase-1 activation ...201121687407
low structural diversity of the o-polysaccharides of photorhabdus asymbiotica subspp. asymbiotica and australis and their similarity to the o-polysaccharides of taxonomically remote bacteria including francisella tularensis.the o-polysaccharides were isolated from the lipopolysaccharides of emerging human pathogens photorhabdus asymbiotica subsp. asymbiotica us-86 and us-87 and subsp. australis au36, au46, and au92. studies by sugar analysis and (1)h and (13)c nmr spectroscopy before and after o-deacetylation showed that the o-polysaccharide structures are essentially identical within, and only slightly different between, the subspecies. the following structures of the repeating units of the o-polysaccharides were ...201121816392
treatment failure of gentamicin in pediatric patients with oropharyngeal tularemia.tularemia is a zoonotic infection, and the causative agent is francisella tularensis. a first-line therapy for treating tularemia is aminoglycosides (streptomycin or, more commonly, gentamicin), and treatment duration is typically 7 to 10 days, with longer courses for more severe cases.201121709631
innate immune recognition of francisella tularensis: activation of type-i interferons and the inflammasome.francisella tularensis is an intracellular pathogen that can cause severe disease in a wide range of mammalian hosts. primarily residing in host macrophages, f. tularensis escapes phagosomal degradation, and replicates in the macrophage cytosol. the macrophage uses a series of pattern recognition receptors to detect conserved microbial molecules from invading pathogens, and initiates an appropriate host response. in the cytosol, f. tularensis is recognized by the inflammasome, a multiprotein com ...201121687410
[streptococcus pneumonia infection and positive blood culture with francisella tularensis, in a renal transplant recipient.] 201121816564
special topic on francisella tularensis and tularemia. 201121833327
francisella-arthropod vector interaction and its role in patho-adaptation to infect mammals.francisella tularensis is a gram-negative, intracellular, zoonotic bacterium, and is the causative agent of tularemia with a broad host range. arthropods such as ticks, mosquitoes, and flies maintain f. tularensis in nature by transmitting the bacteria among small mammals. while the tick is largely believed to be a biological vector of f. tularensis, transmission by mosquitoes and flies is largely believed to be mechanical on the mouthpart through interrupted feedings. however, the mechanism of ...201121687425
leptospirosis and tularaemia in raccoons (procyon lotor) of larimer country, colorado.raccoons (procyon lotor) are commonly implicated as carriers of many zoonotic pathogens. the purpose of this cross-sectional study was to look for leptospira interrogans and francisella tularensis in opportunistically sampled, free-ranging raccoons of larimer country, colorado, usa. sixty-five animals were included in the study and testing consisted of gross post-mortem examination, histopathology, and both immunohistochemistry and pcr for l. interrogans and f. tularensis. no significant gross l ...201121824365
a galu mutant of francisella tularensis is attenuated for virulence in a murine pulmonary model of tularemia.abstract: background: a number of studies have revealed that francisella tularensis (ft) suppresses innate immune responses such as chemokine/cytokine production and neutrophil recruitment in the lungs following pulmonary infection via an unidentified mechanism. the ability of ft to evade early innate immune responses could be a very important virulence mechanism for this highly infectious bacterial pathogen. results: here we describe the characterization of a galu mutant strain of ft live vacci ...201121819572
francisella tularensis 2-c-methyl-d-erythritol 4-phosphate cytidylyltransferase: kinetic characterization and phosphoregulation.deliberate and natural outbreaks of infectious disease, the prevalence of antibiotic resistant strains, and the ease by which antibiotic resistant bacteria can be intentionally engineered all underscore the necessity of effective vaccines and continued development of novel antimicrobial/antiviral therapeutics. isoprenes, a group of molecules fundamentally involved in a variety of crucial biological functions, are derived from either the mevalonic acid (mva) or methylerythritol phosphate (mep) pa ...201121694781
seroprevalence of seven zoonotic infections in nunavik, quebec (canada).in nunavik, common practices and food habits such as consumption of raw meat and untreated water place the inuit at risk for contracting zoonotic diseases. the aim of this study was to determine the seroprevalence of seven zoonotic infections among the permanent residents of nunavik. the study was conducted in the fall 2004 as part of the nunavik health survey. blood samples from adults aged 18-74ôçâyears (nôçâ=ôçâ917) were collected and analysed for the presence of antibodies against trichinell ...201121824376
Phylogeography of Francisella tularensis subspecies holarctica from the country of Georgia.Francisella tularensis, the causative agent of tularemia, displays subspecies-specific differences in virulence, geographic distribution, and genetic diversity. F. tularensis subsp. holarctica is widely distributed throughout the Northern Hemisphere. In Europe, F. tularensis subsp. holarctica isolates have largely been assigned to two phylogenetic groups that have specific geographic distributions. Most isolates from Western Europe are assigned to the B.Br.FTNF002-00 group, whereas most isolates ...201121682874
Development of tolerogenic dendritic cells and regulatory T cells favors exponential bacterial growth and survival during early respiratory tularemia.Tularemia is a vector-borne zoonosis caused by Ft, a Gram-negative, facultative intracellular bacterium. Ft exists in two clinically relevant forms, the European biovar B (holarctica), which produces acute, although mild, self-limiting infections, and the more virulent United States biovar A (tularensis), which is often associated with pneumonic tularemia and more severe disease. In a mouse model of tularemia, respiratory infection with the virulence-attenuated Type B (LVS) or highly virulent Ty ...201121724804
exploitation of host cell biology and evasion of immunity by francisella tularensis.francisella tularensis is an intracellular bacterium that infects humans and many small mammals. during infection, f. tularensis replicates predominantly in macrophages but also proliferate in other cell types. entry into host cells is mediate by various receptors. complement-opsonized f. tularensis enters into macrophages by looping phagocytosis. uptake is mediated in part by syk, which may activate actin rearrangement in the phagocytic cup resulting in the engulfment of f. tularensis in a lipi ...201121687747
administration of a nitric oxide donor inhibits mgla expression by intracellular francisella tularensis and counteracts phagosomal escape and subversion of tnf-α secretion.francisella tularensis is a highly virulent intracellular bacterium capable of rapid multiplication in phagocytic cells. previous studies have revealed that activation of f. tularensis-infected macrophages leads to control of infection and reactive nitrogen and oxygen species make important contributions to the bacterial killing. we investigated the effects of adding s-nitroso-acetyl-penicillamine (snap), which generates nitric oxide, or 3-morpholinosydnonimine hydrochloride, which indirectly le ...201121700740
immunity to francisella.in recent years, studies on the intracellular pathogen francisella tularensis have greatly intensified, generating a wealth of new information on the interaction of this organism with the immune system. here we review the basic elements of the innate and adaptive immune responses that contribute to protective immunity against francisella species, with special emphasis on new data that has emerged in the last 5 years. most studies have utilized the mouse model of infection, although there has bee ...201121687418
aoac smpr 2010.001. standard method performance requirements for polymerase chain reaction (pcr) methods for detection of francisella tularensis in aerosol collection filters and/or liquids. 201121919365
pneumonic tularemia in rabbits resembles the human disease as illustrated by radiographic and hematological changes after infection.pneumonic tularemia is caused by inhalation of the gram negative bacterium, francisella tularensis. because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures.201121931798
francisella infection triggers activation of the aim2 inflammasome in murine dendritic cells.the intracellular bacterium francisella tularensis is the causative agent of tularemia, a potentially fatal disease. in macrophages, francisella escapes the initial phagosome and replicates in the cytosol, where it is detected by the cytosolic dna sensor aim2 leading to activation of the aim2 inflammasome. however, during aerosol infection, francisella is also taken up by dendritic cells. in this study, we show that francisella novicida escapes into the cytosol of bone marrow-derived dendritic c ...201121902795
francisella rna polymerase contains a heterodimer of non-identical alpha subunits.abstract: background: all sequenced genomes of representatives of the francisella genus contain two rpoa genes, which encode non-identical rna polymerase (rnap) subunits, alpha1 and alpha2. in all other bacteria studied to date, a dimer of identical alpha subunits initiates the assembly of the catalytically proficient rnap core (subunit composition (alpha)2/beta/beta'). based on an observation that both alpha1 and alpha2 are incorporated into francisella rnap, charity et al. (2007) previously s ...201122108176
photonic biosensor assays to detect and distinguish subspecies of francisella tularensis.the application of photonic biosensor assays to diagnose the category-a select agent francisella tularensis was investigated. both interferometric and long period fiber grating sensing structures were successfully demonstrated; both these sensors are capable of detecting the optical changes induced by either immunological binding or dna hybridization. detection was made possible by the attachment of dna probes or immunoglobulins (igg) directly to the fiber surface via layer-by-layer electrostati ...201122163782
Clinicopathologic correlation of epidemiologic and histopathologic features of pediatric bacterial lymphadenitis.Infection is a common cause of lymphadenopathy in children and has numerous microbial etiologies. Lymph node biopsy is considered a keystone in arriving at a definite diagnosis. An accurate differential diagnosis from a lymph node biopsy can expedite diagnosis and minimize ancillary testing.201122032579
Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis.Intracellular bacterial pathogens Francisella novicida and the Live Vaccine Strain (LVS) are recognized in the macrophage cytosol by the AIM2 inflammasome, which leads to the activation of caspase-1 and the processing and secretion of active IL-1ß, IL-18 and pyroptosis. Previous studies have reported that F. novicida and LVS mutants in specific genes (e.g. FTT0584, mviN and ripA) induce elevated inflammasome activation and hypercytotoxicity in host cells, leading to the proposal that F. novicida ...201121883803
deletion of iglh in virulent francisella tularensis subsp. holarctica fsc200 strain results in attenuation and provides protection against the challenge with the parental strain.francisella tularensis, the causative agent of tularemia, is a highly infectious intracellular pathogen with no licensed vaccine available today. the recent search for genome sequences involved in f. tularensis virulence mechanisms led to the identification of the 30-kb region defined as a francisella pathogenicity island (fpi). in our previous itraq study we described the concerted upregulation of some fpi proteins in different f. tularensis strains cultivated under stress conditions. among the ...201121930232
iglg and igli of the francisella pathogenicity island are important virulence determinants of francisella tularensis lvs.the gram-negative bacterium francisella tularensis is the causative agent of tularemia, a disease intimately associated with the multiplication of the bacterium within host macrophages. this in turn requires the expression of francisella pathogenicity island (fpi) genes, believed to encode a type vi secretion system. while the exact functions of many of the components have yet to be revealed, some have been found to contribute to the ability of francisella to cause systemic infection in mice as ...201121690239
toward an understanding of the perpetuation of the agent of tularemia.the epidemiology of tularemia has influenced, perhaps incorrectly skewed, our views on the ecology of the agent of tularemia. in particular, the central role of lagomorphs needs to be reexamined. diverse observations, some incidental, and some that are more generally reproducible, have not been synthesized so that the critical elements of the perpetuation of francisella tularensis can be identified. developing a quantitative model of the basic reproduction number of f. tularensis may require sep ...201121687803
francisella subverts innate immune signaling: focus on pi3k/akt.intracellular bacterial pathogens exploit host cells as a part of their lifecycle, and they do so by manipulating host cell signaling events. many such bacteria are known to produce effector proteins that promote cell invasion, alter membrane trafficking, and disrupt signaling cascades. this review highlights recent advances in our understanding of signaling pathways involved in host cell responses to francisella tularensis, a facultative gram-negative intracellular pathogen that causes tularemi ...201121686123
erythema nodosum and sweet's syndrome in patients with glandular tularemia. 201121699525
tlr2 signaling contributes to rapid inflammasome activation during f. novicida infection.background: early detection of microorganisms by the innate immune system is provided by surface-expressed and endosomal pattern recognition receptors (prrs) such as toll-like receptors (tlrs). detection of microbial components by tlrs initiates a signaling cascade leading to the expression of proinflammatory cytokines including il-6 and il-1+¦. some intracellular bacteria subvert the tlr response by rapidly escaping the phagosome and entering the cytosol. however, these bacteria may be recogniz ...201121698237
presence and interaction of inflammatory cells in the spleen of atlantic cod, gadus morhua l., infected with francisella noatunensis.serious infectious diseases, accompanied by macrophage-dominated chronic inflammation, are common in farmed atlantic cod. to increase knowledge relating to morphological aspects of such inflammatory responses, cod were challenged with francisella noatunensis, an important bacterial pathogen of this fish species. tissue and cell dynamics in the spleen were examined sequentially over 60ôçâdays. small clusters of mainly macrophage-like cells (mlcs) staining for non-specific esterase and acid phosph ...201121838712
detection of new francisella-like tick endosymbionts in hyalomma spp. and rhipicephalus spp. (acari: ixodidae) from bulgaria.we report on the identification of two new francisella-like endosymbionts (fles) found in three different tick species from bulgaria. the fles were characterized by 16s rrna and tul4 gene sequencing and seem to lack the molecular marker rd1. these two new taxa seem to be facultative secondary endosymbionts of ticks.201121705542
the subversion of the immune system by francisella tularensis.francisella tularensis is a highly virulent bacterial pathogen and the causative agent of tularemia. perhaps the most impressive feature of this bacterium is its ability to cause lethal disease following inoculation of as few as 15 organisms. this remarkable virulence is, in part, attributed to the ability of this microorganism to evade, disrupt, and modulate host immune responses. the objective of this review is to discuss the mechanisms utilized by f. tularensis to evade and inhibit innate and ...201121687406
seroprevalence of tularemia in wild bears and hares in japan.tularemia is a zoonotic disease caused by francisella tularensis. the distribution of the pathogen in japan has not been studied well. in this study, seroprevalence of tularemia among wild black bears and hares in japan was determined. blood samples collected from 431 japanese black bears (ursus thibetanus japonicus) and 293 japanese hares (lepus brachurus) between 1998 and 2009 were examined for antibodies against f. tularensis by micro-agglutination test (ma) or enzyme-linked immunosorbent ass ...201121824374
regulation of francisella tularensis virulence.francisella tularensis is one of the most virulent bacteria known and a centers for disease control and prevention category a select agent. it is able to infect a variety of animals and insects and can persist in the environment, thus francisella spp. must be able to survive in diverse environmental niches. however, f. tularensis has a surprising dearth of sensory and regulatory factors. recent advancements in the field have identified new functions of encoded transcription factors and greatly e ...201121687801
francisella tularensis osteomyelitis of the hand following a cat bite: a case of clinical suspicion. 201121701312
francisella-átularensis meningitis. 201121831551
the francisella tularensis proteome and its recognition by antibodies.francisella tularensis is the causative agent of a spectrum of diseases collectively known as tularemia. the extreme virulence of the pathogen in humans, combined with the low infectious dose and the ease of dissemination by aerosol have led to concerns about its abuse as a bioweapon. until recently, nothing was known about the virulence mechanisms and even now, there is still a relatively poor understanding of pathogen virulence. completion of increasing numbers of francisella genome sequences, ...201121687770
type iv pili in francisella - a virulence trait in an intracellular pathogen.francisella tularensis is a highly virulent intracellular human pathogen that is capable of rapid proliferation in the infected host. mutants affected in intracellular survival and growth are highly attenuated which highlights the importance of the intracellular phase of the infection. genomic analysis has revealed that francisella encodes all genes required for expression of functional type iv pili (tfp), and in this focused review we summarize recent findings regarding this system in the patho ...201121687421
a variety of novel lipid a structures obtained from francisella tularensis live obtained from francisella tularensis live.f. tularensis is a gram-negative coccobacillus that causes tularemia. its lps has nominal biological activity. currently, there is controversy regarding the structure of the lipid a obtained from f. tularensis live vaccine strain (lvs). therefore, to resolve this controversy, the purification and structural identification of this lps was crucial. to achieve this, lps from f. tularensis lvs was acid hydrolyzed to obtain crude lipid a that was methylated and purified by hplc and the fractions were ...201121709054
suppurative cervical adenopathy and pharyngeal mass due to tularemia unresponsive to medical treatment.tularemia is a zoonotic disease caused by francisella tularensis. tularemia presents with various clinical forms, such as ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal tularemia forms. as an intracellular pathogen, f. tularensis causes granulomatous and suppurative lesions especially in the affected regional lymph nodes and various organs. tularemia is seen most commonly in the black sea and marmara regions of turkey. herein, we describe a girl with tularemi ...201122272458
Human tularemia in France, 2006-2010.Tularemia is an endemic but rare disease in France. We describe the epidemiologic, clinical, diagnostic, treatment, and prognostic aspects of the disease in 101 consecutive patients investigated during a 5-year period (2006-2010).201122002987
association of different genetic types of francisella-like organisms with the rocky mountain wood tick (dermacentor andersoni) and the american dog tick (dermacentor variabilis) from localities near their northern distributional limits.dermacentor andersoni and dermacentor variabilis from allopatric and sympatric populations near their northern distributional limits were examined for the presence of francisella species using molecular techniques that targeted 373 bp of the 16s ribosomal rna gene. although there was no evidence for the presence of francisella tularensis in any tick, francisella-like endosymbionts (fles) were common in d. andersoni and d. variabilis adults and immatures. a significantly greater proportion of fem ...201122179251
[Oropharyngeal tularemia in beta lactam-resistant cervical lymphadenitis].This study aims emphasize oropharyngeal tularemia in the differential diagnosis of infected lymphadenopathy in the neck region.201121919830
[Detection and identification of highly pathogenic bacteria within the framework of the EQADeBa project--Part I: Samples containing living pathogens].Bacillus anthracis, Yersinia pestis, Francisella tularensis, Brucella sp., Bulkholderia mallei are B. pseudomallei are highly pathogenic bacteria of potential bioterrorism risk. To support the early warning and rapid response capacity to ensure an effective reaction to bioterrorist attacks the international project "Establishment of Quality Assurances for Detection of Highly Pathogenic Bacteria of Potential Bioterrorism Risk" (EQADeBa) has been established. The aim of the project was establishme ...201122184939
identification of circulating bacterial antigens by in vivo microbial antigen discovery.detection of microbial antigens in clinical samples can lead to rapid diagnosis of an infection and administration of appropriate therapeutics. a major barrier in diagnostics development is determining which of the potentially hundreds or thousands of antigens produced by a microbe are actually present in patient samples in detectable amounts against a background of innumerable host proteins. in this report, we describe a strategy, termed in vivo microbial antigen discovery (inmad), that we used ...201121846829
Dermacentor andersoni transmission of Francisella tularensis subsp. novicida reflects bacterial colonization, dissemination, and replication coordinated with tick feeding.Ticks serve as biological vectors for a wide variety of bacterial pathogens which must be able to efficiently colonize specific tick tissues prior to transmission. The bacterial determinants of tick colonization are largely unknown, a knowledge gap attributed in large part to the paucity of tools to genetically manipulate these pathogens. In this study, we demonstrated that Francisella tularensis subsp. novicida, for which a complete two-allele transposon mutant library has been constructed, ini ...201121930762
the acid phosphatase acpa is secreted in vitro and in macrophages by francisella spp.francisella tularensis is a remarkably infectious facultative intracellular pathogen that causes the zoonotic disease tularemia. essential to f. tularensis spp. pathogenesis is its ability to escape the destructive phagosomal environment and inhibit the host cell respiratory burst. f. tularensis spp. encode a series of acid phosphatases, which have been reported to play important roles in francisella phagosomal escape, inhibition of the respiratory burst and intracellular survival. however, rigo ...201122184418
francisella asiatica as the causative agent of piscine francisellosis in cultured tilapia (oreochromis sp.) in the united states.francisella asiatica is a gram-negative, pleomorphic, facultative intracellular, bacterial pathogen that causes acute to chronic disease in a wide variety of warm-water cultured and wild fish species. outbreaks of francisellosis in warm water fish have been documented in taiwan, japan, united kingdom, hawaii, and latin america (including costa rica) but the organism has only been reported from the united states on one occasion from hybrid striped bass in california. in 2010, the bacterium was de ...201121908332
Oropharyngeal tularemia mimicking tumoral relapse in a patient with Hodgkin lymphoma in remission.Tularemia is a zoonotic disease caused by Francisella tularensis. The clinical forms mostly depend on the port of entry into humans. Ingestion typically results in the oropharyngeal form and is associated with symptoms such as fever, pharyngitis, cervical lymphadenitis, and suppuration. In this report, we describe a child treated for Hodgkin's disease presenting six years later with a left cervical lymphadenopathy mimicking a relapse.201121853659
francisella tularensis reveals a disparity between human and mouse nlrp3 inflammasome activation.pathogen-triggered activation of the inflammasome complex leading to caspase-1 activation and il-1β production involves similar sensor proteins between mouse and human. however, the specific sensors used may differ between infectious agents and host species. in mice, francisella infection leads to seemingly exclusive activation of the aim2 inflammasome with no apparent role for nlrp3. here we examine the il-1β response of human cells to francisella infection. francisella strains exhibit differen ...201121930705
[detection of natural tularemia foci in mongolia].study of the current spread of natural tularemia foci in mongolia and its epizootic activity evaluation for consequent substantiation of the recommendations for prophylaxis of this disease.201122145346
a broadly applicable approach to t cell epitope identification: application to improving tumor associated epitopes and identifying epitopes in complex pathogens.epitopes are a hallmark of the antigen specific immune response. the identification and characterization of epitopes is essential for modern immunologic studies, from investigating cellular responses against tumors to understanding host/pathogen interactions especially in the case of bacteria with intracellular residence. here, we have utilized a novel approach to identify t cell epitopes exploiting the exquisite ability of particulate antigens, in the form of beads, to deliver exogenous antigen ...201121872603
genetic modification of the o-polysaccharide of francisella tularensis results in an avirulent live attenuated vaccine.background. francisella tularensis, the causative agent of tularemia, is a highly virulent microbe. one significant virulence factor of f. tularensis is the o-polysaccharide (o-ps) portion of the organism's lipopolysaccharide.methods. a wzy (o-antigen polymerase) deletion mutant of ft. live attenuated vaccine strain (ft.lvs), designated ft.lvs::δwzy, was created and evaluated as a live attenuated vaccine. specifically, the mutant's virulence potential and its protective efficacy against type a a ...201121969334
a lysm and sh3-domain containing region of the listeria monocytogenes p60 protein stimulates accessory cells to promote activation of host nk cells.listeria monocytogenes (lm) infection induces rapid and robust activation of host natural killer (nk) cells. here we define a region of the abundantly secreted lm endopeptidase, p60, that potently but indirectly stimulates nk cell activation in vitro and in vivo. lm expression of p60 resulted in increased ifnγ production by naïve nk cells co-cultured with treated dendritic cells (dcs). moreover, recombinant p60 protein stimulated activation of naive nk cells when co-cultured with tlr or cytokine ...201122072975
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