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comparative studies on susceptibility of the mouse (mus musculus) and the vole (microtus arvalis) to listeria monocytogenes and erysipelothrix rhusiopathiae.the susceptibility of mice and voles to intraperitoneal and subcutan injection of virulent strains has been tested comparatively on 261 mice and 120 voles. using various germ-doses, 50 per cent lethality has been established. listeria monocytogenes serovar 1/2a killed mice in doses of 120,000 and 1.5 x 10(6) germs when injected intraperitoneally and subcutaneously and voles in doses of 1800 and 12,000 germs, respectively. thus voles proved 100 to 120 times more susceptible than mice. erysipeloth ...19892517160
transfer of immunity against lethal murine francisella infection by specific antibody depends on host gamma interferon and t cells.both serum and spleen cells from mice immune to francisella tularensis transfer protection to naive recipients. here we characterize the mechanism of protection induced by transfer of immune mouse serum (ims). ims obtained 4 weeks after intradermal infection with 10(3) bacteria of the live vaccine strain (lvs) contained high levels of immunoglobulin g2 (igg2a) and igm (end point titers, 1:16,600 and 1:7,200, respectively) and little igg1, igg2b, or igg3. lvs-specific antibodies were detected 5 d ...19948039881
purified lipopolysaccharide from francisella tularensis live vaccine strain (lvs) induces protective immunity against lvs infection that requires b cells and gamma interferon.previous results have demonstrated that nonspecific protective immunity against lethal francisella tularensis live vaccine strain (lvs) or listeria monocytogenes infection can be stimulated either by sublethal infection with bacteria or by treatment with bacterial dna given 3 days before lethal challenge. here we characterize the ability of purified lipopolysaccharide (lps) from f. tularensis lvs to stimulate similar early protective immunity. treatment of mice with surprisingly small amounts of ...200010722593
a francisella mutant in lipid a carbohydrate modification elicits protective immunity.francisella tularensis (ft) is a highly infectious gram-negative bacterium and the causative agent of the human disease tularemia. ft is designated a class a select agent by the centers for disease control and prevention. human clinical isolates of ft produce lipid a of similar structure to ft subspecies novicida (fn), a pathogen of mice. we identified three enzymes required for fn lipid a carbohydrate modifications, specifically the presence of mannose (flmf1), galactosamine (flmf2), or both ca ...200818266468
identification of immunologic and pathologic parameters of death versus survival in respiratory tularemia.francisella tularensis can cause severe disseminated disease after respiratory infection. the identification of factors involved in mortality or recovery following induction of tularemia in the mouse will improve our understanding of the natural history of this disease and facilitate future evaluation of vaccine candidate preparations. balb/c mice were infected intranasally with the live vaccine strain (lvs) of f. tularensis subsp. holarctica and euthanized at different stages of disease to anal ...200818025095
identification of francisella tularensis himar1-based transposon mutants defective for replication in macrophages.francisella tularensis, the etiologic agent of tularemia in humans, is a potential biological threat due to its low infectious dose and multiple routes of entry. f. tularensis replicates within several cell types, eventually causing cell death by inducing apoptosis. in this study, a modified himar1 transposon (himarft) was used to mutagenize f. tularensis lvs. approximately 7,000 km(r) clones were screened using j774a.1 macrophages for reduction in cytopathogenicity based on retention of the cel ...200717682043
toll-like receptor 2-mediated signaling requirements for francisella tularensis live vaccine strain infection of murine macrophages.francisella tularensis, an aerobic, non-spore-forming, gram-negative coccobacillus, is the causative agent of tularemia. we reported previously that f. tularensis live vaccine strain (lvs) elicited strong, dose-dependent nf-kappab reporter activity in toll-like receptor 2 (tlr2)-expressing hek293t cells and proinflammatory gene expression in primary murine macrophages. herein, we report that f. tularensis lvs-induced murine macrophage proinflammatory cytokine gene and protein expression are over ...200717517865
ectoparasite diversity and exposure to vector-borne disease agents in wild rodents in central coastal california.a survey of wild rodents was performed in the morro bay area of central coastal california to determine serological and polymerase chain reaction (pcr) prevalence of anaplasma phagocytophilum dumler, barbet, bekker, dasch, palmer, ray, rikihisa, and rurangirwa, borrelia burgdorferi johnson, schmidt, hyde, steigerwalt, and brenner, francisella tularensis mccoy, and yersinia pestis yersin; to describe the ectoparasitic fauna on important vector-borne disease hosts; and to determine whether pathoge ...200717427705
attenuation and protective efficacy of an o-antigen-deficient mutant of francisella tularensis lvs.francisella tularensis is a zoonotic, gram-negative coccobacillus that causes tularemia in humans and animals. f. tularensis subspecies tularensis (type a) and f. tularensis subspecies holarctica (type b) are antigenically similar and more virulent than francisella novicida in humans. the genetic locus that encodes the lps o antigen was found to be substantially different between the type b live vaccine strain (lvs) and f. novicida. one lvs-specific gene with homology to a galactosyl transferase ...200717768257
mac-1+ cells are the predominant subset in the early hepatic lesions of mice infected with francisella tularensis.the cell composition of early hepatic lesions of experimental murine tularemia has not been characterized with specific markers. the appearance of multiple granulomatous-necrotic lesions in the liver correlates with a marked increase in the levels of serum alanine transferase and lactate dehydrogenase. francisella tularensis, detected by specific antibodies, can be first noted by day 1 and becomes associated with the lesions by 5 days postinoculation. these lesions become necrotic, with some evi ...200617000726
attenuated francisella novicida transposon mutants protect mice against wild-type challenge.francisella tularensis is the bacterial pathogen that causes tularemia in humans and a number of animals. to date, there is no approved vaccine for this widespread and life-threatening disease. the goal of this study was to identify f. tularensis mutants that can be used in the development of a live attenuated vaccine. we screened f. novicida transposon mutants to identify mutants that exhibited reduced growth in mouse macrophages, as these cells are the preferred host cells of francisella and a ...200616926401
nk cells and gamma interferon coordinate the formation and function of hepatic granulomas in mice infected with the francisella tularensis live vaccine strain.host innate immune responses to many intracellular pathogens include the formation of inflammatory granulomas that are thought to provide a physical barrier between the microbe and host. because two common features of infections with the live vaccine strain (lvs) of francisella tularensis within the mouse liver are the formation of granulomas and the production of gamma interferon (ifn-gamma), we have asked what role ifn-gamma plays in hepatic granuloma formation and function. francisella antige ...200818227174
toll-like receptor 4 (tlr4) does not confer a resistance advantage on mice against low-dose aerosol infection with virulent type a francisella tularensis.francisella tularensis, the causative agent of tularemia, is a gram-negative facultative intracellular bacterium. toll-like receptor (tlr) 4 is considered to be critical for inducing host innate immunity against many gram-negative bacteria including many respiratory pathogens. to determine the role of tlr4 in host defense against airborne f. tularensis infection, tlr4-defective c3h/hej (tlr4(d)) or wild-type c3h/heouj (wt) mice were challenged by low-dose aerosol with type a f. tularensis, and t ...200415458779
respiratory infection with francisella novicida induces rapid dystrophic cardiac calcinosis (dcc).francisella tularensis causes pulmonary tularemia and death in humans when left untreated. here, using a novel aerosol infection model, we show that acute pulmonary francisella novicida infection not only causes pneumonia and liver damage, but also induces dystrophic cardiac calcinosis (dcc) in balb/c mice. c57bl/6 mice also develop pneumonia and hepatic damage, but fail to develop dcc. development of dcc in balb/c mice is associated with significant induction of rankl but not osteopontin in the ...200818400010
type iv pili-mediated secretion modulates francisella virulence.francisella tularensis are the causative agent of the zoonotic disease, tularaemia. among four f. tularensis subspecies, ssp. novicida (f. novicida) is pathogenic only for immunocompromised individuals, while all four subspecies are pathogenic for mice. this study utilized proteomic and bioinformatic approaches to identify seven f. novicida secreted proteins and the corresponding type iv pilus (t4p) secretion system. the secreted proteins were predicted to encode two chitinases, a chitin binding ...200616987180
francisella tularensis lvs initially activates but subsequently down-regulates intracellular signaling and cytokine secretion in mouse monocytic and human peripheral blood mononuclear cells.monocytic cells constitute an important defense mechanism against invading pathogens by recognizing conserved pathogens components. the recognition leads to activation of intracellular pathways involving nuclear factor kappa b (nf-kappab) and mitogen-activated protein kinases (mapk), such as the c-jun nh2-terminal kinase (jnk), and p38. we show that in vitro infection with francisella tularensis results in activation of nf-kappab, phosphorylation of p38 and c-jun, and secretion of tnf-alpha in a ...200515925273
detection of francisella tularensis within infected mouse tissues by using a hand-held pcr thermocycler.the diagnosis of human cases of tularemia often relies upon the demonstration of an antibody response to francisella tularensis or the direct culturing of the bacteria from the patient. antibody response is not detectable until 2 weeks or more after infection, and culturing requires special media and suspicion of tularemia. in addition, handling live francisella poses a risk to laboratory personnel due to the highly infectious nature of this pathogen. in an effort to develop a rapid diagnostic a ...200312574268
the aim2 inflammasome is essential for host defense against cytosolic bacteria and dna viruses.inflammasomes regulate the activity of caspase-1 and the maturation of interleukin 1beta (il-1beta) and il-18. aim2 has been shown to bind dna and engage the caspase-1-activating adaptor protein asc to form a caspase-1-activating inflammasome. using aim2-deficient mice, we identify a central role for aim2 in regulating caspase-1-dependent maturation of il-1beta and il-18, as well as pyroptosis, in response to synthetic double-stranded dna. aim2 was essential for inflammasome activation in respon ...201020351692
detection of francisella tularensis in infected mammals and vectors using a probe-based polymerase chain reaction.we investigated the use of a taqman 5' nuclease assay (5na) directed against the francisella tularensis outer membrane protein (fop) gene and a polymerase chain reaction-enzyme immunoassay (pcr-eia) directed against the tul 4 gene for detection of this organism in experimentally infected mice and in field-collected tick vectors. we also evaluated the use of specially formulated filter paper (fta) for rapid sample preparation. the 5na had a detection limit of 1 pg of genomic dna (<100 colony-form ...200010813490
[focal nature of tularemia along the course of the irtysh-karaganda canal].the results of the epizootological survey of the track of the irtysh-karaganda canal for tularemia for the period of 1971-1982 are presented. out of 928 fecal samples from mouse-hunting birds, 16 contained the specific antigen. from arctic shrews a strain of francisella tularensis was isolated.19846240873
[rise in the epizootic activity of a natural focus of steppe-type tularemia in stavropol territory and its epidemic consequences].one of recurrent autumn and winter rises in the epizootic activity of the steppe-type focus of tularemia in the stavropol territory is described. during the tularemia epizooty of 1981-1982 the population of common voles (microtus arvalis) was very numerous, while the population of house mice (mus musculus) was comparatively scarce. francisella tularensis strains were isolated from different species of rodents (microtus arvalis, mus musculus, apodemus sylvanicus, rattus norvegicus, lepus, etc.), ...19853158139
[brucellosis, tularemia and borreliosis isolated from wild animals captured in ankara, konya, urfa and nevsehir provinces in turkey].621 citellus, 41 mus musculus, 35 microtus, 442 meriones, 70 rattus rattus, 56 turtle, 89 hare, 1 hamster, 1 hedgehog and 1 sea snake, altogether 1379 wild animals were captured in ankara, konya, urfa and nevşehir. neither brucella or francisella tularansis could be isolated nor borrelia could be seen. 1/40-1/80 agglutination titers obtained in 3 out of 134 sera taken from citellus, in 3 out of 264 sera taken from guinea pigs which were inoculated with spleen, liver and kidney suspensions of wil ...1976979704
mir-155 induction by f. novicida but not the virulent f. tularensis results in ship down-regulation and enhanced pro-inflammatory cytokine response.the intracellular gram-negative bacterium francisella tularensis causes the disease tularemia and is known for its ability to subvert host immune responses. previous work from our laboratory identified the pi3k/akt pathway and ship as critical modulators of host resistance to francisella. here, we show that ship expression is strongly down-regulated in monocytes and macrophages following infection with f. tularensis novicida (f.n.). to account for this negative regulation we explored the possibi ...200920041145
francisella tularensis invasion of lung epithelial cells.francisella tularensis, a gram-negative facultative intracellular bacterial pathogen, causes disseminating infections in humans and other mammalian hosts. macrophages and other monocytes have long been considered the primary site of f. tularensis replication in infected animals. however, recently it was reported that f. tularensis also invades and replicates within alveolar epithelial cells following inhalation in a mouse model of tularemia. tc-1 cells, a mouse lung epithelial cell line, were us ...200818426871
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
francisella tularensis strain lvs resides in mhc ii-positive autophagic vacuoles in macrophages.the francisella tularensis strain lvs phagosome disintegrates during the first few hours after bacterial entry and microbes are released to the cytosol. within 12 h both rapid multiplication of microbes and a steep increase of apoptosis of infected macrophages occur. we searched for signals involved in the death of macrophages and detected molecules associated with the autophagy machinery cathepsin d, pten, p53 and lc3, whose levels or modification were influenced by ongoing in vitro tularemic i ...200718450226
early consequences of macrophage-francisella tularensis interaction under the influence of different genetic background in mice.the induction, regulation and expression of protective immunity against francisella tularensis lvs infection is dependent on the results of primary interaction between the cells of host's immunoregulatory system and the microbe. the early events, at least on the side of macrophages, are under the genetic control. to determine the impact of genes that might be involved in the control of resistance to francisella tularensis lvs infection, we have used three different inbred strains of mice with in ...19979232429
tlr4-mediated activation of dendritic cells by the heat shock protein dnak from francisella tularensis.francisella tularensis is the causative agent of tularemia, a severe, debilitating disease of humans and other mammals. as this microorganism is also classified as a "category-a pathogen" and a potential biowarfare agent, there is a need for an effective vaccine. several antigens of f. tularensis, including the heat shock protein dnak, have been proposed for use in a potential subunit vaccine. in this study, we characterized the innate immune response of murine bone marrow-derived dendritic cell ...200818708593
ripa, a cytoplasmic membrane protein conserved among francisella species, is required for intracellular survival.francisella tularensis is a highly virulent bacterial pathogen that invades and replicates within numerous host cell types, including macrophages and epithelial cells. in an effort to better understand this process, we screened a transposon insertion library of the f. tularensis live vaccine strain (lvs) for mutant strains that invaded but failed to replicate within alveolar epithelial cell lines. one such strain isolated from this screen contained an insertion in the gene ftl_1914, which is con ...200818765722
identification of an essential francisella tularensis subsp. tularensis virulence factor.francisella tularensis, the highly virulent etiologic agent of tularemia, is a low-dose intracellular pathogen that is able to escape from the phagosome and replicate in the cytosol. although there has been progress in identifying loci involved in the pathogenicity of this organism, analysis of the genome sequence has revealed few obvious virulence factors. we previously reported isolation of an f. tularensis subsp. tularensis strain schu s4 transposon insertion mutant with a mutation in a predi ...200918981253
tularemia in balb/c and c57bl/6 mice vaccinated with francisella tularensis lvs and challenged intradermally, or by aerosol with virulent isolates of the pathogen: protection varies depending on pathogen virulence, route of exposure, and host genetic background.in order to begin understanding the immunological basis for immunity to tularemia, and to establish a baseline for judging the efficacy of potential novel vaccines, the present study examined the ability of the live vaccine strain of francisella tularensis (f. tularensis) lvs, to elicit immunity in mice against subsequent systemic and aerosol challenge with highly virulent strains of the pathogen. the results show, that infection with lvs protects balb/c mice against systemic challenge with viru ...200312922099
combined deletion of four francisella novicida acid phosphatases attenuates virulence and macrophage vacuolar escape.francisella tularensis is a facultative intracellular pathogen and the etiologic agent of tularemia. it is capable of escape from macrophage phagosomes and replicates in the host cell cytosol. bacterial acid phosphatases are thought to play a major role in the virulence and intracellular survival of a number of intracellular pathogens. the goal of this study was to delete the four primary acid phosphatases (acps) from francisella novicida and examine the interactions of mutant strains with macro ...200818490464
cd4+ t cells are required during priming but not the effector phase of antibody-mediated ifn-gamma-dependent protective immunity against pulmonary francisella novicida infection.we have previously demonstrated the protective efficacy of intranasal vaccination with a defined francisella tularensis subsp. novicida deltaiglc mutant (kkf24) against pulmonary f. novicida u112 challenge. in this study, we further characterized the mechanisms of kkf24-induced immunity. intranasally vaccinated kkf24 c57bl/6 major histocompatibility class (mhc) class ii-/- mice produced minimal antigen-specific interferon (ifn)-gamma and serum antibodies and were highly susceptible (0% survival) ...200818427567
an attenuated strain of the facultative intracellular bacterium francisella tularensis can escape the phagosome of monocytic cells.the facultative intracellular bacterium francisella tularensis is a highly virulent and contagious organism, and little is known about its intracellular survival mechanisms. we studied the intracellular localization of the attenuated human vaccine strain, f. tularensis lvs, in adherent mouse peritoneal cells, in mouse macrophage-like cell line j774a.1, and in human macrophage cell line thp-1. confocal microscopy of infected j774a.1 cells indicated that during the first hour of infection the bact ...200314500514
characterization of rationally attenuated francisella tularensis vaccine strains that harbor deletions in the guaa and guab genes.francisella tularensis, the etiologic agent of tularemia, can cause severe and fatal infection after inhalation of as few as 10 -- 100cfu. f. tularensis is a potential bioterrorism agent and, therefore, a priority for countermeasure development. vaccination with the live vaccine strain (lvs), developed from a type b strain, confers partial protection against aerosal exposure to the more virulent type a strains and provides proof of principle that a live attenuated vaccine strain may be efficacio ...200919368784
generalized tularemia in a vervet monkey (chlorocebus aethiops) and a patas monkey (erythrocebus patas) in a zoo.generalized tularemia was diagnosed in a vervet monkey (chlorocebus aethiops) and a patas monkey (erythrocebus patas), both of which died suddenly in the szeged zoo, szeged, hungary. macroscopic lesions in each animal included disseminated, grayish-white foci in the lungs, lymph nodes, spleen, liver, and kidney. all focal lesions were characterized microscopically as purulent to pyogranulomatous to granulomatous inflammation with necrosis. francisella tularensis subsp. holarctica strains were is ...200919407096
the entry and intracellular multiplication of francisella tularensis in cultured cells: its correlation with virulence in experimental mice.five acriflavine agglutination test-positive (acf+) colonies and five negative (acf-) colonies were isolated from each of the four strains (ebina, cmb2, n9, and schu) of francisella tularensis, and the correlation between the virulence in experimental mice and the entry and intracellular multiplication in cultured mouse fibroblast cells (l-929 cells) was examined. all of the acf- colonies derived from the ebina and cmb2 strains were highly virulent in mice, readily entering and growing well in t ...19938295562
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
rela regulates virulence and intracellular survival of francisella novicida.analysis of the genome of francisella tularensis has revealed few regulatory systems, and how the organism adapts to conditions in different niches is poorly understood. the stringent response is a global stress response mediated by (p)ppgpp. the enzyme rela has been shown to be involved in generation of this signal molecule in a range of bacterial species. we investigated the effect of inactivation of the rela gene in francisella by generating a mutant in francisella novicida. under amino acid ...200919762448
contribution of citrulline ureidase to francisella tularensis strain schu s4 pathogenesis.the citrulline ureidase (ctu) activity has been shown to be associated with highly virulent francisella tularensis strains, including schu s4, while it is absent in avirulent or less virulent strains. a definitive role of the ctu gene in virulence and pathogenesis of f. tularensis schu s4 has not been assessed; thus, an understanding of the significance of this phenotype is long overdue. ctu is a carbon-nitrogen hydrolase encoded by the citrulline ureidase (ctu) gene (ftt0435) on the f. tularens ...200919502406
assessment of low-molecular-weight antioxidants in francisella tularensis infected hosts: comparison of two rodents with different susceptibility to tularemia.bacterium francisella tularensis is the causative agent of tularemia disease. it is a zoonosis accompanied with high mortality when untreated. small rodents and hares, in particular, are natural reservoirs of tularemia. despite physiological similarity of common hosts, tularemia exerts different mortality rates. the pathogenesis of tularemia is still not fully understood. the main pathway is associated with proliferation in macrophages after activation by reactive oxygen species in phagosomes.200920027169
short report: time course of hematogenous dissemination of francisella tularensis a1, a2, and type b in laboratory mice.tularemia is a tick-borne zoonotic bacterial disease. in the united states, human tularemia infections are caused by francisella tularensis subspecies tularensis (type a, clades a1 and a2) or f. tularensis subspecies holarctica (type b). we developed a mouse model that can be used to study the ability of ticks to acquire and transmit fully virulent strains of f. tularensis (a1, a2, and type b). we showed that 1) bacteremia was evident by 2 days post-infection (dpi) for a1, a2, and b, 2) bacterem ...200919190224
genome-wide identification of francisella tularensis virulence determinants.francisella tularensis is a gram-negative pathogen that causes life-threatening infections in humans and has potential for use as a biological weapon. the genetic basis of the f. tularensis virulence is poorly understood. this study screened a total of 3,936 transposon mutants of the live vaccine strain for infection in a mouse model of respiratory tularemia by signature-tagged mutagenesis. we identified 341 mutants attenuated for infection in the lungs. the transposon disruptions were mapped to ...200717420240
glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic th17 cells.cd4(+) t cells are critical for host defense but are also major drivers of immune-mediated diseases. the classical view of th1 and th2 subtypes of cd4(+) t cells was recently revised by the identification of the th17 lineage of cd4(+) t cells that produce il-17, which have been found to be critical in the pathogenesis of autoimmune and other diseases. mechanisms controlling the differentiation of th17 cells have been well described, but few feasible targets for therapeutically reducing th17 cell ...201021191064
effective, broad spectrum control of virulent bacterial infections using cationic dna liposome complexes combined with bacterial antigens.protection against virulent pathogens that cause acute, fatal disease is often hampered by development of microbial resistance to traditional chemotherapeutics. further, most successful pathogens possess an array of immune evasion strategies to avoid detection and elimination by the host. development of novel, immunomodulatory prophylaxes that target the host immune system, rather than the invading microbe, could serve as effective alternatives to traditional chemotherapies. here we describe the ...201020523903
regulation of virulence gene transcripts by the francisella novicida orphan response regulator pmra: role of phosphorylation and evidence of mgla/sspa interaction.francisella tularensis subsp. tularensis is the etiologic agent of tularemia and has been designated a category a biothreat agent by the cdc. tularemia is characterized by replication and dissemination within host phagocytes. intramacrophage growth is dependent upon the regulation of francisella pathogenicity island (fpi) virulence genes, which is poorly understood. two-component regulatory systems (tcs) are widely employed by gram-negative bacteria to monitor and respond to environmental signal ...201020231408
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 ...201121476047
live vaccine strain of francisella tularensis: infection and immunity in mice.the live vaccine strain (lvs) of francisella tularensis caused lethal disease in several mouse strains. lethality depended upon the dose and route of inoculation. the lethal dose for 50% of the mice (ld50) in four of six mouse strains (a/j, balb/chsd, c3h/henhsd, and swr/j) given an intraperitoneal (i.p.) inoculation was less than 10 cfu. for the other two strains tested, c3h/hej and c57bl/6j, the i.p. log ld50 was 1.5 and 2.7, respectively. similar susceptibility was observed in mice inoculated ...19911879918
oral immunization of mice with the live vaccine strain (lvs) of francisella tularensis protects mice against respiratory challenge with virulent type a f. tularensis.francisella tularensis is a gram-negative intracellular bacterium, and the causative agent of tularemia. the infection can be initiated by various routes and can manifest itself in several clinical forms with the disseminated typhoidal form initiated by inhalation being most fatal. the attenuated live vaccine strain (lvs), developed almost 50 years ago, remains the sole effective tularemia vaccine, which is still only available as an investigational new drug for at-risk individuals. this vaccine ...200717346863
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 ...201021687776
dynamics of a tularemia outbreak in a closely monitored free-roaming population of wild house mice.infectious disease outbreaks can be devastating because of their sudden occurrence, as well as the complexity of monitoring and controlling them. outbreaks in wildlife are even more challenging to observe and describe, especially when small animals or secretive species are involved. modeling such infectious disease events is relevant to investigating their dynamics and is critical for decision makers to accomplish outbreak management. tularemia, caused by the bacterium francisella tularensis, is ...201526536232
complement sensitivity and factor h binding of european francisella tularensis ssp. holarctica strains in selected animal species.francisella tularensis is a gram-negative bacterium, the causative agent of the zoonotic disease tularaemia. the bacterium has developed several extracellular and intracellular strategies to evade the hosts' innate and adaptive immune responses. the aims of the study were to examine complement sensitivity of wild and attenuated f. tularensis ssp. holarctica strains in animal hosts of distinct sensitivity to the bacterium, to compare the complement-evading ability of wild strains of different phy ...201526551418
role of neutrophils and nadph phagocyte oxidase in host defense against respiratory infection with virulent francisella tularensis in mice.francisella tularensis subspecies (subsp.) tularensis is a cdc category a biological warfare agent and inhalation of as few as 15 bacilli can initiate severe disease. relatively little is known about the cellular and molecular mechanisms of host defense against respiratory infection with subsp. tularensis. in this study, we examined the role of neutrophils and nadph phagocyte oxidase in host resistance to pulmonary infection in a mouse intranasal infection model. we found that despite neutrophil ...201121277990
development of functional and molecular correlates of vaccine-induced protection for a model intracellular pathogen, f. tularensis lvs.in contrast with common human infections for which vaccine efficacy can be evaluated directly in field studies, alternative strategies are needed to evaluate efficacy for slowly developing or sporadic diseases like tularemia. for diseases such as these caused by intracellular bacteria, serological measures of antibodies are generally not predictive. here, we used vaccines varying in efficacy to explore development of clinically useful correlates of protection for intracellular bacteria, using fr ...201222275868
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
[investigation of the presence of francisella tularensis by culture, serology and molecular methods in mice of thrace region, turkey].tularemia is a disease that has been reported in turkey since 1936. although mice are considered to have a role in the transmission of francisella tularensis to man, this has not been exactly confirmed yet. the aim of this study was to investigate the presence of f. tularensis in mice by using culture, serology and molecular methods. for this purpose, four villages (edirne-demirkoy, kirklareli-kaynarca, tekirdag-muzruplu, tekirdag-sinanli) were selected in thrace region of turkey where tularemia ...201424819259
diagnosis of tularemia using piezoelectric biosensor technology.a piezoelectric immunosensor for indirect diagnosis of tularemic infection in mouse serum was developed. francisella tularensis lvs antigen was covalently immobilized on the sensing surface using cystamine and glutaraldehyde for activation and modification of the gold electrode. the normal mouse serum (nms) and serum prepared from mice immunized by escherichia coli were used as negative controls providing signal of 28hz during a 5min interaction. the tularemic infectious (immunized) mouse serum ...200719071403
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
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
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