Publications
| Title | Abstract | Year Filter  | PMID(sorted ascending) Filter  | 
|---|
| 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 ... | 2011 | 21464086 | 
| 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 ... | 2011 | 21466282 | 
| 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 ... | 2011 | 21467996 | 
| 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 ... | 2011 | 21472520 | 
| [real time pcr hybridization for the rapid and specific identification of francisella tularensis]. | tularemia is highly infectious and fatal zoonotic disease caused by gram negative bacteria francisella tularensis. the necessity to undergo medical treatment in early phase of illness in humans and possibility of making use of bacterial aerosol by terrorists in an attack create an urgent need to implement a rapid and effective method which enables to identify the agent. in our study two primers fopa f/r and hybridization probes fopa s1/s2 designed from fopa gene sequence, were tested for their p ... | 2010 | 21473100 | 
| rapid onset of icam-1 expression is a marker of effective macrophages activation during infection of francisella tularensis lvs in vitro. | francisella tularensis is capable to modulate immunobiological activities of the host cells. we focused on the expression of icam-1 (cd54) on j774.2 mouse macrophage cell line infected by f. tularensis live vaccine strain (lvs) in vitro as a putative marker of subsequent elimination of infection. j774.2 cell line cells were infected by f. tularensis lvs strain (multiplicity of infection, 1:100). cell cultures were stimulated either 3 h before infection or 3 h after infection by either lipopolysa ... | 2011 | 21476047 | 
| evasion of ifn-γ signaling by francisella novicida is dependent upon francisella outer membrane protein c. | francisella tularensis is a gram-negative facultative intracellular bacterium and the causative agent of the lethal disease tularemia. an outer membrane protein (ftt0918) of f. tularensis subsp. tularensis has been identified as a virulence factor. we generated a f. novicida (f. tularensis subsp. novicida) ftn_0444 (homolog of ftt0918) fopc mutant to study the virulence-associated mechanism(s) of ftt0918. | 2011 | 21483828 | 
| outbreak of tularaemia in central norway, january to march 2011. | from january to march 2011, 39 cases of tularaemia were diagnosed in three counties in central norway: 21 cases of oropharyngeal type, 10 cases of glandular/ulceroglandular type, two of respiratory and two of typhoid type. three cases were asymptomatic and clinical information was unavailable for one case. the mean age was 40.3 years (range 2-89 years). thirty-four reported use of drinking water from private wells. an increased rodent (lemming) population and snow melting may have led to contami ... | 2011 | 21489376 | 
| formulation and stabilization of francisella tularensis live vaccine strain. | francisella tularensis live vaccine strain (f. tularensis lvs), a promising vaccine candidate for protection against f. tularensis exposure, is a particularly thermolabile vaccine and difficult to stabilize sufficiently for storage under refrigerated conditions. our preliminary data show that f. tularensis lvs can be stabilized in the dried state using foam drying, a modified freeze drying method, with sugar-based formulations. the process was conducted under mild drying conditions, which result ... | 2011 | 21491457 | 
| tlr4-dependent activation of inflammatory cytokine response in macrophages by francisella elongation factor tu. | the bacterial determinants of pulmonary francisella induced inflammatory responses and their interaction with host components are not clearly defined. in this study, proteomic and immunoblot analyses showed presence of a cytoplasmic protein elongation factor tu (ef-tu) in the membrane fractions of virulent francisella novicida, lvs and schus4, but not in an attenuated f. novicida mutant. ef-tu was immunodominant in mice vaccinated and protected from virulent f. novicida. moreover, recombinant ef ... | 2011 | 21497800 | 
| ulceroglandular tularemia. | an increasing number of patients with the zoonosis tularemia have been reported in the last few years in europe. tularemia can be divided into different forms depending on its appearance. tularemia must be considered in the differential diagnosis of diseases that present with an ulcer and regional lymphadenopathy. the diagnosis can be confirmed by culturing francisella tularensis. with effective antibiotic intervention, the prognosis is favorable. typically tularemia develops after outdoor activ ... | 2011 | 21501382 | 
| structure of francisella tularensis peptidyl-trna hydrolase. | the rational design of novel antibiotics for bacteria involves the identification of inhibitors for enzymes involved in essential biochemical pathways in cells. in this study, the cloning, expression, purification, crystallization and structure of the enzyme peptidyl-trna hydrolase from francisella tularensis, the causative agent of tularemia, was performed. the structure of f. tularensis peptidyl-trna hydrolase is comparable to those of other bacterial peptidyl-trna hydrolases, with most residu ... | 2011 | 21505237 | 
| comparative study of immune status to infectious agents in elderly patients with multiple myeloma, waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance. | whereas patients with multiple myeloma (mm) have a well-documented susceptibility to infections, this has been less studied in other b-cell disorders, such as waldenstrom's macroglobulinemia (wm) and monoclonal gammopathy of undetermined significance (mgus). we investigated the humoral immunity to 24 different pathogens in elderly patients with mm (n = 25), wm (n = 16), and mgus (n = 18) and in age-matched controls (n = 20). antibody titers against pneumococci, staphylococcal alpha-toxin, tetanu ... | 2011 | 21508164 | 
| brucellosis of the european brown hare (lepus europaeus). | the european brown hare (lepus europaeus) is an important reservoir of brucella suis biovar 2 and also of the life-threatening zoonotic agent francisella tularensis. since both bacteria can produce similar gross pathological lesions in this species, laboratory tests are necessary for the final diagnosis. the aim of the present study was to develop an immunohistochemical method for the detection of b. suis infection and to describe the pathological and histological lesions caused by b. suis in eu ... | 2011 | 21511271 | 
| tularemia vaccines: recent developments and remaining hurdles. | francisella tularensis subsp. tularensis is a facultative intracellular bacterial pathogen of humans and other mammals. its inhaled infectious dose is very low and can result in very high mortality. historically, subsp. tularensis was developed as a biological weapon and there are now concerns about its abuse as such by terrorists. a live attenuated vaccine developed pragmatically more than half a century ago from the less virulent holarctica subsp. is the sole prophylactic available, but it rem ... | 2011 | 21526941 | 
| transstadial transmission of francisella tularensis holarctica in mosquitoes, sweden. | in sweden, human cases of tularemia caused by francisella tularensis holarctica are assumed to be transmitted by mosquitoes, but how mosquito vectors acquire and transmit the bacterium is not clear. to determine how transmission of this bacterium occurs, mosquito larvae were collected in an area where tularemia is endemic, brought to the laboratory, and reared to adults in their original pond water. screening of adult mosquitoes by real-time pcr demonstrated f. tularensis lpna sequences in 14 of ... | 2011 | 21529386 | 
| differential chitinase activity and production within francisella species, subspecies and subpopulations. | genotyping of francisella tularensis (a1a, a1b, a2 and type b) and francisella novicida has identified multiple differences between species, and among f. tularensis subspecies and subpopulations. variations in virulence, geographic distribution and ecology are also known to exist among this group of bacteria, despite the >95% nucleotide identity in their genomes. this study expands the description of phenotypic differences by evaluating the ability of f. tularensis and f. novicida to degrade chi ... | 2011 | 21531796 | 
| a central metabolic circuit controlled by qsec in pathogenic escherichia coli. | the qsec sensor kinase regulates virulence in multiple gram-negative pathogens, by controlling the activity of the qseb response regulator. we have previously shown that qsec deletion interferes with dephosphorylation of qseb thus unleashing what appears to be an uncontrolled positive feedback loop stimulating increased qseb levels. deletion of qsec downregulates virulence gene expression and attenuates enterohaemorrhagic and uropathogenic escherichia coli (ehec and upec), salmonella typhimurium ... | 2011 | 21542868 | 
| isolation and mutagenesis of a capsule-like complex (clc) from francisella tularensis, and contribution of the clc to f. tularensis virulence in mice. | francisella tularensis is a category-a select agent and is responsible for tularemia in humans and animals. the surface components of f. tularensis that contribute to virulence are not well characterized. an electron-dense capsule has been postulated to be present around f. tularensis based primarily on electron microscopy, but this specific antigen has not been isolated or characterized. | 2011 | 21544194 | 
| comparative evaluation of automated and manual commercial dna extraction methods for detection of francisella tularensis dna from suspensions and spiked swabs by real-time polymerase chain reaction. | this study evaluated commercial automated and manual dna extraction methods for the isolation of francisella tularensis dna suitable for real-time polymerase chain reaction (pcr) analysis from cell suspensions and spiked cotton, foam, and polyester swabs. two automated methods, the magna pure compact and the qiacube, were compared to 4 manual methods, the it 1-2-3 dna sample purification kit, the masterpure complete dna and rna purification kit, the qiaamp dna blood mini kit, and the ultraclean ... | 2011 | 21546201 | 
| non-fcεr bearing mast cells secrete sufficient interleukin-4 to control francisella tularensis replication within macrophages. | mast cells have classically been implicated in the triggering of allergic and anaphylactic reactions. however, recent findings have elucidated the ability of these cells to selectively release a variety of cytokines leading to bacterial clearance through neutrophil and dendritic cell mobilization, and suggest an important role in innate host defenses. our laboratory has established a primary bone marrow derived mast cell-macrophage co-culture system and found that mast cells mediated a significa ... | 2011 | 21565523 | 
| pathology in practice. francisella tularensis. | 2011 | 21568771 | |
| inhibition of francisella tularensis lvs infection of macrophages results in a reduced inflammatory response: evaluation of a therapeutic strategy for intracellular bacteria. | f. tularensis is an intracellular pathogen and is able to invade several different cell types, in particular macrophages, most commonly through phagocytosis. a flow cytometric assay was developed to measure bacterial uptake, using a fitc-labelled anti-f. tularensis lps antibody in conjunction with antibodies to cell surface markers, in order to determine specific cell phenotypes that were positive for the bacteria. several phagocytic inhibitors, were evaluated in macrophage cell lines and a lung ... | 2011 | 21569124 | 
| the rna chaperone hfq is important for growth and stress tolerance in francisella novicida. | the rna-binding protein hfq is recognized as an important regulatory factor in a variety of cellular processes, including stress resistance and pathogenesis. hfq has been shown in several bacteria to interact with small regulatory rnas and act as a post-transcriptional regulator of mrna stability and translation. here we examined the impact of hfq on growth, stress tolerance, and gene expression in the intracellular pathogen francisella novicida. we present evidence of hfq involvement in the abi ... | 2011 | 21573133 | 
| tularaemia in berlin - two independent cases in travellers returning from central anatolia, turkey, february 2011. | 2011 | 21586267 | |
| francisella tularensis membrane complexome by blue native/sds-page. | the study of membrane proteins and membrane protein complexes (mpc) provides crucial information in the field of bacterial physiology and pathogenesis research. the method of blue native polyacrylamide gel electrophoresis and its combination with sds-page (bn/sds-page) were here employed to study the membrane complexome of an intracellular bacterium francisella tularensis, the causative agent of a severe disease tularemia. in the presented study we describe the subunit composition and stoichiome ... | 2011 | 21601022 | 
| impact of francisella tularensis pilin homologs on pilus formation and virulence. | francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. virulence factors for this bacterium, particularly those that facilitate host cell interaction, remain largely uncharacterized. however, genes homologous to those involved in type iv pilus structure and assembly, including six genes encoding putative major pilin subunit proteins, are present in the genome of the highly virulent schu s4 strain. to analyze the roles of three putative pilin genes i ... | 2011 | 21605655 | 
| discovery of a role for hsp82 in histoplasma virulence through a quantitative screen for macrophage lethality. | the application of forward genetics can reveal new factors required for the virulence of intracellular pathogens. to facilitate such virulence screens, we developed macrophage cell lines with which the number of intact host cells following infection with intracellular pathogens can be rapidly and easily ascertained through the expression of a constitutive lacz transgene. using known virulence mutants of francisella novicida and histoplasma capsulatum, we confirmed the applicability of these host ... | 2011 | 21606189 | 
| 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 ... | 2011 | 21607086 | 
| evidence of circulation of an epidemic strain of francisella tularensis in france by multispacer typing. | multispacer typing (mst) was used to type ten francisella tularensis strains detected in french patients. incorporating 79 swedish f. tularensis strains, phylogenetic analysis demonstrated that although tularemia appears as a sporadic disease in france, it is caused by an epidemic cluster of strains. | 2011 | 21611870 | 
| arthropod-borne tularemia in poland: a case report. | abstract tularemia is a rare zoonosis. the most common way is ingestion of contaminated meat or water, but the infection may also be acquired by insect bite. the clinical picture of the disease may be nonspecific. due to polymorphisms of clinical picture, specific treatment is often delayed. in the last 50 years, in poland, the most infections were acquired by handling hares. in our article, we present the case of a patient who was infected with francisella tularensis due to arthropod bite. in t ... | 2011 | 21612529 | 
| differential mortality of dog tick vectors due to infection by diverse francisella tularensis tularensis genotypes. | abstract the factors involved in the long-term perpetuation of francisella tularensis tularensis in nature are poorly understood. martha's vineyard, massachusetts, has become a site of sustained transmission of type a tularemia, with nearly 100 human cases reported from 2000 to 2010. we have identified a stable focus of f. tularensis transmission there, where the annual prevalence in host-seeking dermacentor variabilis is about 3%, suggesting that this tick perpetuates the agent. however, labora ... | 2011 | 21612530 | 
| francisella tularensis molecular typing using differential insertion sequence amplification (disa). | tularemia is a potentially fatal disease that is caused by the highly infectious and zoonotic pathogen francisella tularensis. despite the monomorphic nature of sequenced f. tularensis genomes, there is a significant degree of plasticity in the organization of genetic elements. the observed variability in these genomes is primarily due to the transposition of direct repeats and insertion sequence (is) elements. since current methods used to genotype f. tularensis are time-consuming and require e ... | 2011 | 21613430 | 
| cellulitis, headache, and fever following tick bites. | 2011 | 21617001 | |
| 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 ... | 2011 | 21623848 | 
| 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 ... | 2011 | 21625462 | 
| francisella tularensis: a red-blooded pathogen. | 2011 | 21628652 | |
| 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 ... | 2011 | 21628658 | 
| 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 ... | 2011 | 21632711 | 
| 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 ... | 2011 | 21637805 | 
| [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 ... | 2011 | 21644066 | 
| 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 ... | 2011 | 21645622 | 
| 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 ... | 2011 | 21661327 | 
| 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 ... | 2011 | 21666011 | 
| 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 ... | 2011 | 21669537 | 
| 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 ... | 2011 | 21670171 | 
| 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 ... | 2011 | 21682874 | 
| 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 ... | 2011 | 21686123 | 
| 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 ... | 2011 | 21687406 | 
| 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 ... | 2011 | 21687407 | 
| 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 ... | 2011 | 21687410 | 
| 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 ... | 2011 | 21687418 | 
| 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 ... | 2011 | 21687421 | 
| 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 ... | 2011 | 21687425 | 
| 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 ... | 2011 | 21687747 | 
| the role of the francisella tularensis pathogenicity island in type vi secretion, intracellular survival, and modulation of host cell signaling. | francisella tularensis is a highly virulent gram-negative intracellular bacterium that causes the zoonotic disease tularemia. essential for its virulence is the ability to multiply within host cells, in particular monocytic cells. the bacterium has developed intricate means to subvert host immune mechanisms and thereby facilitate its intracellular survival by preventing phagolysosomal fusion followed by escape into the cytosol, where it multiplies. moreover, it targets and manipulates numerous h ... | 2010 | 21687753 | 
| francisella tularensis metabolism and its relation to virulence. | francisella tularensis is a gram-negative bacterium capable of causing the zoonotic disease tularaemia in a large number of mammalian species and in arthropods. f. tularensis is a facultative intracellular bacterium that infects and replicates in vivo mainly inside macrophages. during its systemic dissemination, f. tularensis must cope with very different life conditions (such as survival in different target organs or tissues and/or survival in the blood streamôçª) and may thus encounter a broad ... | 2010 | 21687763 | 
| 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, ... | 2011 | 21687770 | 
| francisella tularensis blue-gray phase variation involves structural modifications of lipopolysaccharide o-antigen, core and lipid a and affects intramacrophage survival and vaccine efficacy. | francisella tularensis is a cdc category a biological agent and a potential bioterrorist threat. there is no licensed vaccine against tularemia in the united states. a long-standing issue with potential francisella vaccines is strain phase variation to a gray form that lacks protective capability in animal models. comparisons of the parental strain (lvs) and a gray variant (lvsg) have identified lipopolysaccharide (lps) alterations as a primary change. the lps of the f. tularensis variant strain ... | 2010 | 21687776 | 
| 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 ... | 2011 | 21687801 | 
| 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 ... | 2011 | 21687803 | 
| the francisella intracellular life cycle: toward molecular mechanisms of intracellular survival and proliferation. | the tularemia-causing bacterium francisella tularensis is a facultative intracellular organism with a complex intracellular lifecycle that ensures its survival and proliferation in a variety of mammalian cell types, including professional phagocytes. because this cycle is essential to francisella pathogenesis and virulence, much research has focused on deciphering the mechanisms of its intracellular survival and replication and characterizing both bacterial and host determinants of the bacterium ... | 2010 | 21687806 | 
| 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 ... | 2011 | 21690239 | 
| 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 ... | 2011 | 21694781 | 
| 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 ... | 2011 | 21698237 | 
| erythema nodosum and sweet's syndrome in patients with glandular tularemia. | 2011 | 21699525 | |
| 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 ... | 2011 | 21700740 | 
| francisella tularensis osteomyelitis of the hand following a cat bite: a case of clinical suspicion. | 2011 | 21701312 | |
| 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. | 2011 | 21705542 | 
| 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 ... | 2011 | 21709054 | 
| 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. | 2011 | 21709631 | 
| 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 ... | 2011 | 21724804 | 
| 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 ... | 2011 | 21747796 | 
| 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 ... | 2011 | 21747799 | 
| 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 ... | 2011 | 21750122 | 
| 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 ... | 2011 | 21753150 | 
| 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 ... | 2011 | 21767345 | 
| 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. | 2011 | 21784318 | 
| 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 ... | 2011 | 21789257 | 
| outbreak of tularaemia in brown hares (lepus europaeus) in france, january to march 2011. | 2011 | 21794224 | |
| 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 ... | 2011 | 21797037 | 
| 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 ... | 2011 | 21799828 | 
| 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 ... | 2011 | 21803089 | 
| 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 ... | 2011 | 21803910 | 
| 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 ... | 2011 | 21803994 | 
| 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 ... | 2011 | 21804002 | 
| 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 ... | 2011 | 21813776 | 
| 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 ... | 2011 | 21816392 | 
| [streptococcus pneumonia infection and positive blood culture with francisella tularensis, in a renal transplant recipient.] | 2011 | 21816564 | |
| 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 ... | 2011 | 21819572 | 
| 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 ... | 2011 | 21824365 | 
| 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 ... | 2011 | 21824374 | 
| 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 ... | 2011 | 21824376 | 
| francisella-átularensis meningitis. | 2011 | 21831551 | |
| special topic on francisella tularensis and tularemia. | 2011 | 21833327 | |
| 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 ... | 2011 | 21838712 | 
| transmission efficiency of francisella tularensis by adult american dog ticks (acari: ixodidae). | the american dog tick, dermacentor variabilis (say) (acari: ixodidae), has been implicated as a potential bridging vector to humans of francisella tularensis, the etiological agent of tularemia. since the initial studies evaluating vector competency of d. variabilis were conducted, f. tularensis has been subdivided into subspecies and clades that differ in their geographical distribution in the united states and in the severity of infections caused in humans. here, we demonstrate that d. variabi ... | 2011 | 21845949 | 
| 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 ... | 2011 | 21846829 | 
| a francisella tularensis schu s4 mutant deficient in γ-glutamyltransferase activity induces protective immunity: characterization of an attenuated vaccine candidate. | francisella tularensis is an intracellular pathogen which causes tularaemia. there is no licensed vaccine currently available for prophylaxis. the γ-glutamyl transpeptidase (ggt) encoded by the ggt gene has been shown to be important for the intracellular survival of f. tularensis. in this study we have constructed a ggt deletion mutant in the highly virulent f. tularensis strain schu s4. characterization of the mutant strain confirmed the function of ggt, and confirmed the role of ggt in cystei ... | 2011 | 21852349 | 
| 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. | 2011 | 21853659 |