Publications

vaccines against francisella tularensis--past, present and future.	francisella tularensis is a facultative intracellular bacterial pathogen capable of causing a spectrum of human diseases collectively called tularemia. the pathogen is highly infectious and some strains can cause rapidly lethal infection especially when inhaled. the latter were developed as biological weapons in the past and nowadays cause concern as potential bioterrorism agents. a live attenuated strain of the pathogen was developed more that 40 years ago and remains the sole prophylactic meas ...	2004	15176947
characterisation of the core part of the lipopolysaccharide o-antigen of francisella novicida (u112).	francisella novicida (u112), a close relative of the highly virulent bacterium f. tularensis, is known to produce a lipopolysaccharide that is significantly different in biological properties from the lps of f. tularensis. here we present the results of the structural analysis of the f. novicida lps core part, which is found to be similar to that of f. tularensis, differing only by one additional alpha-glc residue:where r is an o-chain, linked via a beta-bacillosamine (2,4-diamino-2,4,6-trideoxy ...	2004	15183739
methods for enhanced culture recovery of francisella tularensis.	francisella tularensis is found in a wide variety of hosts and extrahost environments, making culture recovery a diagnostic challenge. here we demonstrate improved recovery times and good sensitivity (90%) when cultures were inoculated on the site of an investigation using fresh tissues. for contaminated specimens, antibiotic supplementation of enriched cysteine heart agar blood culture medium improved recovery of f. tularensis by 81.1%. for transport of tissues, immediate freezing yielded cultu ...	2004	15184180
mgla regulates transcription of virulence factors necessary for francisella tularensis intraamoebae and intramacrophage survival.	francisella tularensis is able to survive and grow within macrophages, a trait that contributes to pathogenesis. several genes have been identified that are important for intramacrophage survival, including mgla and iglc. f. tularensis is also able to survive within amoebae. it is shown here that f. tularensis mgla and iglc mutant strains are not only defective for survival and replication within the macrophage-like cell line j774, but also within acanthamoebae castellanii. moreover, these strai ...	2004	15010524
[multilocus vntr-typing of francisella tularensis strains].	in the analysis of f. tularensis genome with the use of the specially developed program "dna" a great number of loci containing tandem repeats were found. for analysis, 3 of them were selected and designated as fta, ftb, ftc. the study of dna of 40 f. tularensis strains in the polymerase chain reaction with specific primers to these loci a great variability in the number of repeats was established, the presence of 17 alleles being found in locus fta, 5 alleles in locus ftb and 5 alleles in locus ...	2004	15188553
[experimental study on the possibility of using live tularemia vaccine to increase resistance to heterologous infection disease].	in experiments on guinea pigs immunized with francisella tularensis 15, or live tularemia vaccine (ltv), the level of heterologous protective effect to dangerous infectious diseases caused by yersinia pestis, burkholderia pseudomallei, b. mallei, mycobacterium tuberculosis was studied. the study revealed that during the first 4 weeks after the subcutaneous immunization with ltv the level of resistance of the immunized animals to heterologous infective agent reliably increased as indicated by the ...	2004	15188557
immunobiology of the tomatine adjuvant.	soluble or sub-unit protein vaccines alone are incapable of generating antigen-specific cellular immune responses. this failure can be attributed to the manner in which the immune system processes antigen; endogenous antigens are cycled through the mhc class i pathway to stimulate cd8+ restricted responses and exogenous antigens are processed through the mhc class ii pathway to generate humoral immunity. traditionally sub-unit vaccines have been formulated with adjuvants to enhance immunogenicit ...	2004	15193398
an outbreak of tularemia in western black sea region of turkey.	the aim of this study was to investigate the source and the size of a tularemia outbreak in a village located in a non-endemic area. five patients from the same village were admitted to hospital with the same complaints all within one week of september 2001. tularemia was suspected and a diagnosis was made after physical and anamnesis examinations. the village was visited the same week that the patients were admitted to the hospital, in the january and april 2002. the villagers were examined and ...	2004	15004863
histologic and molecular diagnosis of tularemia: a potential bioterrorism agent endemic to north america.	francisella tularensis (ft), a zoonotic bacterium that causes tularemia, has received attention as a possible bioterrorism threat. we developed a pcr assay for use in fixed, processed tissues, which are safer to handle and allow archival testing. pcr analysis for a 211-bp fragment of the ft lipoprotein gene was performed on tissues from 16 cases of tularemia. in all, 14/15 cases with intact dna (93%) were positive for ft by pcr. frequent histologic findings in pcr-positive tissues included irreg ...	2004	15001997
protection afforded by heat shock protein 60 from francisella tularensis is due to copurified lipopolysaccharide.	heat shock proteins (hsps) have attracted significant attention as protective antigens against a range of diseases caused by bacterial pathogens. however, more recently there have been suggestions that the protective response is due to the presence of peptide components other than hsps. we have shown that mice that had been immunized with purified heat shock protein 60 (hsp60) isolated from francisella tularensis were protected against a subsequent challenge with some strains of the bacterium. h ...	2004	15213156
serologic survey for selected disease agents in wolves (canis lupus) from alaska and the yukon territory, 1984-2000.	wolves (canis lupus) were captured in several geographic areas of alaska (usa) and the yukon territory (canada) during 1984-2000. blood was collected from 1,122 animals. sera were tested for antibodies against infectious canine hepatitis virus (ich), canine distemper virus (cdv), canine parvovirus (cpv), francisella tularensis, and serovars of leptospira interrogans. antibody prevalence for ich was >84% for all areas. area-specific prevalences of antibodies ranged from 12% to 70% for cpv, from 0 ...	2004	15650081
construction and characterization of a highly efficient francisella shuttle plasmid.	francisella tularensis is a facultative intracellular pathogen that infects a wide variety of mammals and causes tularemia in humans. it is recognized as a potential agent of bioterrorism due to its low infectious dose and multiple routes of transmission. to date, genetic manipulation in francisella spp. has been limited due to the inefficiency of dna transformation, the relative lack of useful selective markers, and the lack of stably replicating plasmids. therefore, the goal of this study was ...	2004	15574954
[tularemia from a cat bite].	we report the first case in norway of a man who developed ulceroglandular tularaemia following a cat bite. if after feline contact, patients develop skin and soft-tissue infections that fail to respond to therapy with penicillin, physicians should consider the possibility of tularaemia. our patient was successfully treated with ciprofloxacin, which is effective against francisella tularensis and most pathogens associated with feline infections. a greater awareness of infections following a cat b ...	2004	15608764
concomitant or consecutive infection with coxiella burnetii and tickborne diseases.	q fever is a worldwide zoonosis caused by coxiella burnetii, which can be isolated from ticks. reports of people with both q fever and other tickborne diseases are rare. in this study, we describe 6 patients with q fever who were infected with 1 of the following tickborne pathogens: rickettsia conorii (2 patients), rickettsia slovaca (2), rickettsia africae (1), and francisella tularensis (1).	2004	15614696
intranasal interleukin-12 treatment promotes antimicrobial clearance and survival in pulmonary francisella tularensis subsp. novicida infection.	francisella tularensis is a highly virulent facultative intracellular bacterium and is considered a potential biological warfare agent. inhalation tularemia can lead to the development of bronchopneumonia, which is frequently fatal without medical intervention. treatment strategies that directly target the respiratory mucosa may extend the efficacy of therapy, particularly for the medical management of acute aerosol exposure. to this end, we describe an intranasal (i.n.) strategy for the treatme ...	2004	15561819
[bite wound infections].	the lifetime risk of experiencing a bite wound, human or animal, is approximately 50%, and bite wounds account for approximately 1% of all visits to emergency departments. the majority of bite wounds are inflicted by dogs and cats.	2004	15608763
early activation of nk cells after lung infection with the intracellular bacterium, francisella tularensis lvs.	francisella tularensis is a gram-negative intracellular bacterium that has been classified as a category a biothreat because of its ability to induce deadly pneumonic tularemia when inhaled. in the present study, an experimental model of f. tularensis lvs intranasal infection was used to study the immune cells involved in cytokine secretion in the lungs after infection. dramatic increases in the numbers of cells secreting ifn-gamma were observed 72 h after intranasal infection of balb/c and c57b ...	2004	15922718
tularaemia: bioterrorism defence renews interest in francisella tularensis.	francisella tularensis is a highly infectious aerosolizable intracellular pathogen that is capable of causing a debilitating or fatal disease with doses as low as 25 colony-forming units. there is no licensed vaccine available. since the 1950s there has been concern that f. tularensis could be used as a biological threat agent, and it has received renewed attention recently owing to concerns about bioterrorism. the international conference on tularaemia in 2003 attracted more than 200 delegates, ...	2004	15550942
tularaemia outbreak in bulgaria.	during the last 40 y, 2 large tularaemia outbreaks occurred in bulgaria. we report the second outbreak, in 1998--2003, including a total of 262 laboratory confirmed cases. the majority of the patients presented with oropharyngeal tularaemia (89.7%). less common were the glandular, pulmonary and oculoglandular forms. the diagnosis of tularaemia was confirmed serologically. in 5 cases, f. tularensis was detected by immunofluorescent assay in lymph node biopsies. by pcr, all 5 samples yielded succe ...	2004	15764161
repeatability and pattern recognition of bacterial fatty acid profiles generated by direct mass spectrometric analysis of in situ thermal hydrolysis/methylation of whole cells.	direct ci mass spectrometry profiling of fatty acid methyl esters (fames) from in situ thermal hydrolysis/methylation (thm) of whole bacterial cells with tetramethylammonium hydroxide (tmah) has been demonstrated as a potential method for real time and fieldable detection/identification of microorganisms. bacillus anthracis (ames), yersinia pestis (nair. kenya), vibrio cholerae (e1 tor), brucella melitensis (abortus wild) and francisella tularensis (lvs vaccine) were profiled by this method duri ...	2003	18968943
clinical and epidemiological characteristic of tularemia in kazakhstan.	from 1950 to 1977, 5049 human tularemia cases were registered that had been associated with a large number of non-immunized people coming to kazakh tularemia endemic areas from different places of soviet union to harvest the grain. since 1978, the number of tularemia patients has considerably decreased and during 1992-2001 thirty-one human cases were reported. epidemiological analysis showed that infection was transmitted by a variety of routes, including bites of infected arthropod, ingestion o ...	2003	15029832
ecological conditions of natural foci of tularaemia in the czech republic.	tularaemia, a zoonosis of veterinary and public health importance, commonly occurs in the czech republic as well as other countries of northern hemisphere. the objective of this study was to analyse the environmental conditions of distribution of natural foci of tularaemia and their long-term persistence in the czech republic. a geographic information system has been used for this purpose. a new variable (chi(t)), the mean number of natural foci in a specific area, has been suggested for the eva ...	2003	14620945
allelic exchange in francisella tularensis using pcr products.	we describe here a technique for allelic exchange in francisella tularensis subsp. novicida utilizing polymerase chain reaction (pcr) products. linear pcr fragments containing gene deletions with an erythromycin resistance cassette insertion were transformed into f. tularensis. the subsequent ermr progeny were found to have undergone allelic exchange at the correct location in the genome; the minimum flanking homology necessary was 500 bp. this technique was used to create mgla, iglc, bla, and t ...	2003	14680699
causes of febrile illnesses after a tick bite in slovenian children.	to establish the etiology in slovenian children with febrile illnesses occurring after a tick bite.	2003	14688569
[gene typing of infectious tularemia strains isolated from the stavropol and krasnodar territories].	the typing of f. tularensis strains by four variable number of tandem repeats (vntr) loci has been carried out. among the strains isolated in the stavropol and krasnodar territories seven genotypes have been detected and their spread in different natural foci has been analyzed. the data thus obtained suggest that the vntr analysis may become an important instrument for studying the structure of the natural foci of tularemia and evolutionary relationships between individual areas of these foci.	2003	14716980
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 ...	2003	14500514
tularemia.	tularemia is a complex clinical disorder caused by the ubiquitous intracellular parasite francisella tularensis, which has many mammalian and insect hosts. the peak observed incidence of tularemia occurred in 1939, and most present-day clinicians have never seen a case of this disease. tularemia manifests several different clinical syndromes, depending on the portal of entry. f. tularensis has been used in biological warfare experimentation and it has been weaponized and stockpiled in the past b ...	2003	14505277
molecular diagnostic techniques for use in response to bioterrorism.	the use of micro-organisms as agents of biological warfare is considered inevitable for several reasons, including ease of production and dispersion, delayed onset of symptoms, ability to cause high rates of morbidity and mortality and difficulty in diagnosis. therefore, the clinical presentation and pathogenesis of the organisms posing the highest threat (variola major, bacillus anthracis, yersinia pestis, clostridium botulinum toxin, francisella tularensis, filoviruses, arenaviruses and brucel ...	2003	14510181
myositis and septicaemia caused by francisella tularensis biovar holarctica.	a case of tularaemia presenting with severe septicaemia and myositis is reported. the infection was presumed to be acquired by a bite from the horse fly haematopota pluvialis, also known as the rain fly.	2003	14514156
infectious diseases. an obscure weapon of the cold war edges into the limelight.		2003	14551418
prevention and treatment of bacterial diseases caused by bacterial bioterrorism threat agents.	there is general consensus that the bacterial agents or products most likely to be used as weapons of mass destruction are bacillus anthracis, yersinia pestis, francisella tularensis and the neurotoxin of clostridium botulinum. modern supportive and antimicrobial therapy for inhalational anthrax is associated with a 45% mortality rate, reinforcing the need for better adjunctive therapy and prevention strategies. pneumonic plague is highly contagious, difficult to recognize and is frequently fata ...	2003	14554016
[comparative study of ixodes ticks on their infection with tularemia pathogen using biologic and serological assays].	the paper presents the results of a long-term comparative study of the infection of ixodes tick imagoes with the pathogen of tularemia by using the biological assay and antibody neutralization test. the infection rates determined by both methods were found to be identical or close. if there was a difference in the rates in some years, it was not statistically significant. a statistically significant difference could not be found in the infection rates for ticks and in the dependence on their spe ...	2003	14564840
epizootiologic and ecologic investigations of european brown hares (lepus europaeus) in selected populations from schleswig-holstein, germany.	from 1997-99 european brown hare (lepus europaeus) population densities were estimated by spotlight surveys within different areas in schleswig-holstein, germany. these areas showed a wide variation in local hare population densities. in addition, red fox (vulpes vulpes) densities were estimated in 1997 by surveys of fox dens and litters. sera of 321 hares (shot between 1998-2000) from four study areas were examined for antibodies against european brown hare syndrome virus (ebhsv) by enzyme link ...	2003	14733269
[sero-epidemiological studies of zoonotic infections in hunters--comparative analysis with veterinarians, farmers, and abattoir workers].	the aim of this study was to investigate seroprevalences to zoonotic pathogens in hunters, to compare the results with other predisposed occupational groups already investigated and to propose preventive measures. blood samples were taken from 146 male and 3 female hunters from the provinces of styria and burgenland in the south-east of austria and anamnestic data were obtained using a questionnaire. the serological investigations included the following bacterial, viral and parasitic zoonotic ag ...	2003	15508783
development of a multitarget real-time taqman pcr assay for enhanced detection of francisella tularensis in complex specimens.	tularemia is the zoonotic disease caused by the gram-negative coccobacillus francisella tularensis. its wide distribution in the environment poses a challenge for understanding the transmission, ecology, and epidemiology of the disease. f. tularensis is also considered a potential biological weapon due to its extreme infectivity. we have developed a multitarget real-time taqman pcr assay capable of rapidly and accurately detecting f. tularensis in complex specimens. targeted regions included the ...	2003	14662930
glandular tularemia in a native american child.	this case report details the clinical manifestation and course of glandular tularemia, an uncommon but significant cause of cervical lymphadenopathy in children. we discuss the unique attributes of this disease along with appropriate steps that lead to early identification of the organism and effective treatment. the potential use of the organism as a bioterrorism agent is another interesting aspect of this entity.	2003	14661434
bacterial biofilms of importance to medicine and bioterrorism: proteomic techniques to identify novel vaccine components and drug targets.	biofilms are highly ordered microbial communities enmeshed in a carefully sculpted matrix designed for survival of organisms either in multi- or mono-genus/species in a specific microniche. in human disease, biofilm infections are some of the most recalcitrant to treat. even with rigorous antibiotic regimens, some biofilms, such as those within the thick airway mucus of cystic fibrosis (cf) patients, persist throughout the course of the disease process. in this editorial, discussion will cover t ...	2003	14640945
mechanisms of pathogenesis: evasion of killing by polymorphonuclear leukocytes.	few microorganisms evade killing by neutrophils. summarized here are the mechanisms used by yersinia, group a streptococci, helicobacter, ehrlichia and francisella to block phagocytosis, disrupt phagosome maturation or perturb the respiratory burst. also discussed are mechanisms used by neutrophils to control organisms that replicate inside macrophages.	2003	14613776
liposome delivery of ciprofloxacin against intracellular francisella tularensis infection.	the effect of liposome delivery on the controlled release and therapeutic efficacy of ciprofloxacin against intracellular francisella tularensis infection in vivo was evaluated in this study. ciprofloxacin was encapsulated in small unilamellar vesicles by a remote loading procedure using an ammonium sulfate gradient. this procedure produced uniform sized liposomes (100 nm) with an entrapment rate of 90+/-3.5%. following administration of unencapsulated or liposome-encapsulated ciprofloxacin by i ...	2003	14568408
francisella: a little bug hits the big time.		2003	14711357
[germs and toxins in bioterrorism].		2003	12722194
[modern possibilities of bioterrorism diagnosis].	one of the most important components of early detecting and response to biological attack are microbiological diagnostic methods. in order to provide the effectiveness of diagnosis continuous training in detection of potentially dangerous bioterrorist agents is needed. basic information about selected microbiological agents most dangerous for public health, belonging to a and b cdc categories are presented in the article. the most potent biological weapon mentioned in the last decade is anthrax. ...	2003	12728676
[tularemia possibly transmitted by red swamp crayfish].		2003	12729545
experimental tularemia in mice challenged by aerosol or intradermally with virulent strains of francisella tularensis: bacteriologic and histopathologic studies.	balb/c and c57bl/6 mice were challenged by aerosol or intradermally with low doses ( approximately 10-20 colony forming units) of virulent type a and type b strains of the facultative intracellular pathogen, francisella tularensis, and the course of infection was monitored. both mouse strains were equally susceptible to infection, but type a strains reached lethal numbers a few days earlier than type b strains regardless of challenge route. balb/c mice showed overt signs of infection for several ...	2003	12732472
tularemia of the head and neck: a possible sign of bioterrorism.	recent bioterror attacks and other world events have focused the medical community's attention on agents that might be used in biological warfare. one of these potential biological weapons is francisella tularensis, a gramnegative coccobacillus that is one of the most infectious bacteria known. f tularensis can cause severe, even fatal, systemic tularemia. under normal circumstances, f tularensis is transmitted by infected ticks, insects, and other animals. as a weapon of terrorism, the bacteriu ...	2003	12735158
francisella novicida lps has greater immunobiological activity in mice than f. tularensis lps, and contributes to f. novicida murine pathogenesis.	to further understand the role of lps in the pathogenesis of francisella infection, we characterized murine infection with f. novicida, and compared immunobiological activities of f. novicida lps and the lps from f. tularensis live vaccine strain (lvs). f. novicida had a lower intradermal ld(50) in balb/cbyj mice than f. tularensis lvs, and mice given a lethal f. novicida dose intraperitoneally died faster than those given the same lethal f. tularensis lvs dose. however, the pattern of in vivo d ...	2003	12737995
a case of primary tularemic pneumonia presenting with necrotizing mediastinal and hilar lymph nodes.	tularemia is an unusual disease caused by the gram-negative coccobacillus francisella tularensis. the clinical features of the disease depend on the route of inoculation. ulceroglandular and typhoidal forms have been recognized as occurring in tularemia, however primary or secondary pneumonic infections have also been reported. symptoms, laboratory markers and radiological features are non-specific in tularemic pneumonia. diagnosis is made on clinical grounds and evidence of elevated agglutinati ...	2003	12741082
a method for allelic replacement in francisella tularensis.	a vector for mutagenesis of francisella tularensis was constructed based on the puc19 plasmid. by inserting the sacb gene of bacillus subtilis, orit of plasmid rp4, and a chloramphenicol resistance gene of shigella flexneri, a vector, ppv, was obtained that allowed specific mutagenesis. a protocol was developed that allowed introduction of the vector into the live vaccine strain, lvs, of f. tularensis by conjugation. as a proof of principle, we aimed to develop a specific mutant defective in exp ...	2003	12770718
towards proteome database of francisella tularensis.	the accessibility of the partial genome sequence of francisella tularensis strain schu 4 was the starting point for a comprehensive proteome analysis of the intracellular pathogen f. tularensis. the main goal of this study is identification of protein candidates of value for the development of diagnostics, therapeutics and vaccines. in this review, the current status of 2-de f. tularensis database building, approaches used for identification of biologically important subsets of f. tularensis pro ...	2003	12659739
genome-wide dna microarray analysis of francisella tularensis strains demonstrates extensive genetic conservation within the species but identifies regions that are unique to the highly virulent f. tularensis subsp. tularensis.	francisella tularensis is a potent pathogen and a possible bioterrorism agent. little is known, however, to explain the molecular basis for its virulence and the distinct differences in virulence found between the four recognized subspecies, f. tularensis subsp. tularensis, f. tularensis subsp. mediasiatica, f. tularensis subsp. holarctica, and f. tularensis subsp. novicida. we developed a dna microarray based on 1,832 clones from a shotgun library used for sequencing of the highly virulent stra ...	2003	12843022
francisella strains express hemolysins of distinct characteristics.	historically, francisella strains have been described as nonhemolytic. in this study, we show by use of solid and liquid hemolysis assays that some francisella strains have hemolytic properties. the francisella novicida type strain u112 is hemolytic to horse erythrocytes and francisella philomiragia type strain fsc144 is hemolytic towards both human and horse erythrocytes. the f. novicida strain u112 released a protein (novilysin a) into the culture supernatant which cross-reacted with antiserum ...	2003	12855173
expression cloning and biochemical characterization of a rhizobium leguminosarum lipid a 1-phosphatase.	lipid a of rhizobium leguminosarum, a nitrogen-fixing plant endosymbiont, displays several significant structural differences when compared with escherichia coli. an especially striking feature of r. leguminosarum lipid a is that it lacks both the 1- and 4'-phosphate groups. distinct lipid a phosphatases that attack either the 1 or the 4' positions have previously been identified in extracts of r. leguminosarum and rhizobium etli but not sinorhizobium meliloti or e. coli. here we describe the id ...	2003	12869541
characterization of a novicida-like subspecies of francisella tularensis isolated in australia.	francisella tularensis is found throughout the northern hemisphere, where it is associated with the disease of tularaemia in animals and humans. the isolation and identification is reported of a novicida-like subspecies of f. tularensis from a foot wound sustained in brackish water in the northern territory of australia.	2003	12909664
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 ...	2003	12922099
tularemia presenting as tonsillopharyngitis and cervical lymphadenitis: a case report and review of the literature.	in this report, we describe a 57-year-old woman with oropharyngeal tularemia who presented with tonsillopharyngitis and cervical lymphadenitis. clinical and radiological manifestations and histopathological characteristics of this disease are discussed with a review of the world literature. the oropharyngeal form of tularemia should be considered in the differential diagnosis of cases involving tonsillopharyngitis and cervical lymphadenitis, particularly in those not responding to penicillin tre ...	2003	12883950
multiple t cell subsets control francisella tularensis lvs intracellular growth without stimulation through macrophage interferon gamma receptors.	a variety of data suggest that in vivo production of interferon (ifn)-gamma is necessary, but not sufficient, for expression of secondary protective immunity against intracellular pathogens. to discover specific ifn-gamma-independent t cell mediated mechanisms, we took advantage of an in vitro culture system that models in vivo immune responses to the intracellular bacterium francisella tularensis live vaccine strain (lvs). lvs-immune lymphocytes specifically controlled 99% of the growth of lvs ...	2003	12885873
[the role of lipopolysaccharide in toxicity of francisella genus bacteria].	it was demonstrated that the lipopolysaccharides (lps) preparations, which were isolated from all representatives of francisella genus bacteria, i.e. f. tularensis, f. novicida, f. novicida-like and f. philomiragia by using the method of r.p. darveau, r.e. hancock (1983), were not toxic for white rats and white mice. a comparative study of toxicity of live f. tularensis bacteria (both wild and lps-defective strains) made it possible to establish a direct correlation between the toxicity of micro ...	2003	12966923
identifying and subtyping species of dangerous pathogens by automated ribotyping.	an investigation of dangerous bacterial pathogens was conducted to determine the usefulness of automated rrna operon ribotyping (riboprinter system) to identify species. a total of 26 isolates comprising bacillus anthracis, brucella spp., burkholderia mallei, francisella tularensis, and yersinia pestis were tested using restriction endonucleases ecori, psti, pvuii and asei. the main problem was that the system's database-relying on ecori as restriction enzyme-does not contain the essential dange ...	2003	12967744
characterization of the o antigen gene cluster and structural analysis of the o antigen of francisella tularensis subsp. tularensis.	a gene cluster encoding enzymes involved in lps o antigen biosynthesis was identified from the partial genome sequence of francisella tularensis subsp. tularensis schu s4. all of the genes within the cluster were assigned putative functions based on sequence similarity with genes from o antigen biosynthetic clusters from other bacteria. ten pairs of overlapping primers were designed to amplify the o antigen biosynthetic cluster by pcr from nine strains of f. tularensis. although the gene cluster ...	2003	12972577
specific antibodies contribute to the host protection against strains of francisella tularensis subspecies holarctica.	t cells are crucial to the control and eradication of the facultative intracellular bacterium francisella tularensis. a contributory role of humoral antibodies in the host defence remains to be assessed. we used b-cell-deficient mice to study the possible contribution of antibodies to the defence against the live vaccine strain (lvs) or a clinical isolate of f. tularensis, both belonging to the subspecies holarctica (type b). when b-cell-deficient (igmu(-/-)) mice of the c57bl/10 background were ...	2003	12901846
[seroepidemiological studies of zoonotic infections in hunters in southeastern austria--prevalences, risk factors, and preventive methods].	the aim of this study was to investigate the seroprevalences to zoonotic pathogens in hunters, to propose preventive measures and to obtain more information about the occurrence of zoonotic pathogens in local wild animal populations. from 146 male and 3 female hunters originating from the south-eastern austrian federal states of styria and burgenland blood samples were taken and anamnestic data were obtained using a questionnaire. the serological investigations included the following viral, bact ...	2003	12894685
francisella tularensis inhibits toll-like receptor-mediated activation of intracellular signalling and secretion of tnf-alpha and il-1 from murine macrophages.	microbial ligands, including lipopolysaccharide (lps) and bacterial lipoproteins, activate toll-like receptors (tlr) of mononuclear phagocytes, thereby inducing proinflammatory cytokines and antimicrobial activity. we show that francisella tularensis, an intracellular pathogen, is capable of inhibiting this macrophage response. infection with the live vaccine strain f. tularensis lvs rendered cells of the murine macrophage-like cell line j774a.1 incapable of secreting tnf-alpha or il-1beta and m ...	2003	12542469
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 ...	2003	12574268
fatal infection caused by francisella tularensisin a neutropenic bone marrow transplant recipient.	francisella tularensis is one of the most infectious pathogenic bacteria known. even though immunity against this organism is thought to be primarily t cell mediated, some evidence suggests that neutrophils may also play an important protective role. we report a case of tularemia in a neutropenic bone marrow transplant recipient that sheds light on the importance of neutrophils in protection against this infection and review clinical aspects of this fascinating infection emphasizing areas of int ...	2003	12574964
[tularemia ("rabbit plague")].		2003	12596770
mice intradermally-inoculated with the intact lipopolysaccharide, but not the lipid a or o-chain, from francisella tularensis lvs rapidly acquire varying degrees of enhanced resistance against systemic or aerogenic challenge with virulent strains of the pathogen.	the present study examines the relationship between the structure and important biological effects of the lipopolysaccharide (lps) of the intracellular bacterial pathogen, francisella tularensis lvs. it shows that treating mice with sub-immunogenic amounts of intact f. tularensis lps rapidly induces an enhanced resistance to intradermal or aerogenic challenge with strains of the pathogen of varying virulence. however, neither the free lipid a nor core-o-chain produced by mild acid hydrolysis of ...	2003	12620383
tularemia on martha's vineyard: seroprevalence and occupational risk.	we conducted a serosurvey of landscapers to determine if they were at increased risk for exposure to francisella tularensis and to determine risk factors for infection. in martha's vineyard, massachusetts, landscapers (n=132) were tested for anti-f. tularensis antibody and completed a questionnaire. for comparison, serum samples from three groups of nonlandscaper martha's vineyard residents (n=103, 99, and 108) were tested. twelve landscapers (9.1%) were seropositive, compared with one person to ...	2003	12643831
capillary electrophoresis and fluorescence studies on molecular beacon-based variable length oligonucleotide target discrimination.	molecular beacons (mbs) are oligonucleotide probes having a compact hairpin structure, with a fluorophore attached to one end and a quencher molecule attached to the other end. in its native state, the fluorophore is quenched by virtue of its proximity to the quencher molecule. upon hybridization with its complementary oligonucleotide target, fluorescence is elicited due to a conformational change that results in separation of the fluorophore and quencher molecule. the present study describes th ...	2003	12652574
tick salivary gland extract accelerates proliferation of francisella tularensis in the host.	accelerated proliferation of the tick-borne bacterial pathogen francisella tularensis was demonstrated in mice when the bacterium was injected together with salivary gland extract from ixodes ricinus ticks. a significant increase in the numbers of bacteria was recorded in the dermal site of infection,the draining lymph nodes, and the spleen. analysis of the expression of cytokine messenger ribonucleic acids showed polarization toward a th2 profile. salivary gland extract-mediated suppression of ...	2003	12659297
molecular evidence for novel tick-associated spotted fever group rickettsiae from thailand.	ticks are of considerable medical and veterinary importance because they directly harm the host through their feeding action and indirectly through vectoring many bacterial pathogens. despite many ticks being known from thailand, very little is known about the bacteria they may harbor. we report here the results of a survey of tick-associated bacteria in thailand. a total of 334 individuals representing 14 species of ticks in five genera were collected from 10 locations in thailand and were exam ...	2003	12693853
rabbit's revenge.		2003	12781506
francisella tularensis bacteremia.	bacteremia caused by francisella tularensis is rare and has been reported mainly in the united states and infrequently in europe. we report herein the first case of bacteremic f. tularensis pneumonia in an immunocompetent individual in southern europe.	2003	12791928
molecular characterization of the sucb gene encoding the immunogenic dihydrolipoamide succinyltransferase protein of bartonella vinsonii subsp. berkhoffii and bartonella quintana.	members of the genus bartonella have historically been connected with human disease, such as cat scratch disease, trench fever, and carrion's disease, and recently have been recognized as emerging pathogens causing other clinical manifestations in humans. however, because little is known about the antigens that elicit antibody production in response to bartonella infections, this project was undertaken to identify and molecularly characterize these immunogens. immunologic screening of a bartonel ...	2003	12874367
a vaccine for tularaemia.	francisella tularensis is an intracellular pathogen with a very low infectious dose for humans. several forms of tularaemia occur, which range from a severely debilitating to a fatal disease. diagnosis is difficult due to the generalised, nonspecific nature of symptoms and the difficulty in culturing the slow-growing and nutritionally fastidious pathogen. a live attenuated vaccine strain (lvs) has been used in humans as an investigational new drug and does appear to induce a protective response. ...	2003	12831369
genetic diversity of bacterial agents detected in ticks removed from asymptomatic patients in northeastern italy.	a total of 360 ticks were removed from 353 asymptomatic subjects in belluno province, italy and surrounding areas, from 1998 to 2001. ticks were identified as ixodes ricinus (357), ixodes hexagonus (1), rhipicephalus sanguineus (1), and ixodes ventalloi (1). tick dna was investigated by pcr and subsequent sequencing of amplified products to identity associated bacterial agents. primers targeting different genes of rickettsia (glta and ompa), borrelia (16s rdna, rpob), francisella (16s rdna), and ...	2003	12860623
missed sentinel case of naturally occurring pneumonic tularemia outbreak: lessons for detection of bioterrorism.	family physicians are likely to care for patients that have been exposed to diseases associated with bioterrorism. persons with seemingly nondescript initial disease symptoms could be harbingers of a larger outbreak, whether naturally occurring or purposefully created.	2003	12949036
serologic survey for diseases in free-ranging coyotes (canis latrans) from two ecologically distinct areas of utah.	the influence of habitat and associated prey assemblages on the prevalence of canine diseases in coyotes (canis latrans) has received scant attention. from december 1997 through december 1999, we captured 67 coyotes in two ecologically distinct areas of utah (usa): deseret land and livestock ranch and us army dugway proving ground. these areas differ in habitat and prey base. we collected blood samples and tested for evidence of various canine diseases. prevalence of antibodies against canine pa ...	2003	12910777
francisella tularensis selectively induces proinflammatory changes in endothelial cells.	naturally acquired infections with francisella tularensis, the bacterial agent of tularemia, occur infrequently in humans. however, the high infectivity and lethality of the organism in humans raise concerns that it might be exploited as a weapon of bioterrorism. despite this potential for illicit use, the pathogenesis of tularemia is not well understood. to examine how f. tularensis interacts with cells of its mammalian hosts, we tested the ability of a live vaccine strain (lvs) to induce proin ...	2003	12928407
delineation of the molecular mechanisms of francisella tularensis-induced apoptosis in murine macrophages.	francisella tularensis is a facultative intracellular bacterium capable of inducing apoptosis in murine macrophages. here we analyzed the pathway leading to apoptosis in the murine macrophage-like cell line j774a.1 after infection with f. tularensis strain lvs (named lvs for live vaccine strain). we obtained evidence that the infection affected the mitochondria of the macrophages, since it induced release of the mitochondrial molecule cytochrome c into the cytosol and changed the potential over ...	2003	12874344
[tularemia, a potential bioterrorism weapon].	a potential weapon: because of its highly contagious nature with a low inoculum, principally with the biovar a, f. tularensis is considered as an agent that could be used by terrorists, notably when sprayed. any epidemic of tularemia, essentially in its respiratory form, particularly in areas of low incidence of this infection, should be suspected to be a biowarfare attack. the voluntary contamination of water with this bacteria could also be used as a biological weapon. the different forms of t ...	2003	12947746
survival and growth of francisella tularensis in acanthamoeba castellanii.	francisella tularensis is a highly infectious, facultative intracellular bacterium which causes epidemics of tularemia in both humans and mammals at regular intervals. the natural reservoir of the bacterium is largely unknown, although it has been speculated that protozoa may harbor it. to test this hypothesis, acanthamoeba castellanii was cocultured with a strain of f. tularensis engineered to produce green fluorescent protein (gfp) in a nutrient-rich medium. gfp fluorescence within a. castella ...	2003	12514047
discrimination of human pathogenic subspecies of francisella tularensis by using restriction fragment length polymorphism.	we describe the use of two insertion sequence elements (isftu1 and isftu2) in francisella tularensis to type strains by restriction fragment length polymorphism (rflp). the rflp profiles of 17 epidemiologically unrelated isolates were determined and compared. our results showed that rflp profiles can be used to assign f. tularensis strains into five main groups corresponding to strains of f. tularensis subsp. tularensis, f. tularensis strain atcc 6223, strains of f. tularensis subsp. holarctica, ...	2003	12517824
the ascendancy of amblyomma americanum as a vector of pathogens affecting humans in the united states.	until the 1990s, amblyomma americanum was regarded primarily as a nuisance species, but a tick of minor importance as a vector of zoonotic pathogens affecting humans. with the recent discoveries of ehrlichia chaffeensis, ehrlichia ewingii, and "borrelia lonestari," the public health relevance of lone star ticks is no longer in question. during the next 25 years, the number of cases of human disease caused by a. americanum-associated pathogens will probably increase. based on current trajectories ...	2003	12414740
[prevalence of antibodies against francisella tularensis in castilla y león (spain) before 1997].	the aim of this paper was determine the prevalence of antibodies against francisella tularensis in the representative sample of people from castilla-león (spain) before epidemic outbreak of end 1997.	2003	12605730
tularaemia.	tularaemia is a zoonotic bacterial disease of the northern hemisphere. the causative agent, francisella tularensis, is spread to humans by direct contact with infected rodents or lagomorphs, aerogenic exposure, ingestion of contaminated food or water, or by arthropod bites. the prevalence of tularaemia shows a wide geographic variation. in some endemic regions, outbreaks occur frequently, whereas nearby rural parts of a country may be completely free. f. tularensis is a facultative intracellular ...	2003	12608453
virulence determinants and protective antigens of francisella tularensis.	very little is known about virulence mechanisms of the highly virulent bacterium francisella tularensis. specific genetic features of f. tularensis have been obstacles for the development of effective tools for genetic manipulation. however, recent genomic sequencing and large-scale proteomic work have resulted in a substantial increase in the knowledge of f. tularensis. there is also a paucity of information on potential vaccine candidates. recent work assessing the protective efficacy of the f ...	2003	12615222
serologic evidence of human infection by francisella tularensis in the population of castilla y león (spain) prior to 1997.	prior to an outbreak in castilla y león in december 1997, tularaemia was practically non-existent in spain. in this paper we studied the prevalence of antibodies against francisella tularensis in a representative sample of the population (4825 people) from castilla y león (spain) in samples collected before this outbreak. antibodies against f. tularensis were detected in nine (0.19%) of the 4825 sera, with antibody titres ranging from 1/20 to 1/160. of these nine sera, one was positive in seroag ...	2003	12628554
[tularemia in inactive natural foci].	the data on the epidemiological and epizootological manifestations of tularemia on the territory of the ulyanovsk region are presented. the characteristics describing the process of the of francisella tularensis circulation as well as the environmental objects, most important for the manifestations of tularemia infection, are given.	2003	12630366
will the enigma of francisella tularensis virulence soon be solved?	francisella tularensis is one of the most infectious bacterial pathogens known and is the causative agent of the zoonotic disease tularemia. in spite of the importance of this pathogen little is known about its virulence mechanisms. however, it is clear that the bacterium is an intracellular pathogen, replicating mainly in macrophages, with replication in amoebae also having been reported. the genome sequence of a high virulence strain of f. tularensis is close to completion and when available, ...	2003	12648943
innate and adaptive immune responses to an intracellular bacterium, francisella tularensis live vaccine strain.	the immune response to intracellular bacterium, francisella tularensis, which causes tularemia and is proposed to be a potential bioterrorism pathogen, has been studied in mice using the attenuated live vaccine strain (lvs). here we review this infection model, which provides a convenient means of studying protective immune mechanisms not only for francisella, but also for the large and important class of intracellular pathogens.	2003	12650771
nine-analyte detection using an array-based biosensor.	a fluorescence-based multianalyte immunosensor has been developed for simultaneous analysis of multiple samples. while the standard 6 x 6 format of the array sensor has been used to analyze six samples for six different analytes, this same format has the potential to allow a single sample to be tested for 36 different agents. the method described herein demonstrates proof of principle that the number of analytes detectable using a single array can be increased simply by using complementary mixtu ...	2002	12498211
genotyping of francisella tularensis strains by pulsed-field gel electrophoresis, amplified fragment length polymorphism fingerprinting, and 16s rrna gene sequencing.	we evaluated three molecular methods for identification of francisella strains: pulsed-field gel electrophoresis (pfge), amplified fragment length polymorphism (aflp) analysis, and 16s rrna gene sequencing. the analysis was performed with 54 francisella tularensis subsp. holarctica, 5 f. tularensis subsp. tularensis, 2 f. tularensis subsp. novicida, and 1 f. philomiragia strains. on the basis of the combination of results obtained by pfge with the restriction enzymes xhoi and bamhi, pfge reveale ...	2002	12149360
the genus caedibacter comprises endosymbionts of paramecium spp. related to the rickettsiales (alphaproteobacteria) and to francisella tularensis (gammaproteobacteria).	obligate bacterial endosymbionts of paramecia able to form refractile inclusion bodies (r bodies), thereby conferring a killer trait upon their ciliate hosts, have traditionally been grouped into the genus caedibacter: of the six species described to date, only the paramecium caudatum symbiont caedibacter caryophilus has been phylogenetically characterized by its 16s rrna gene sequence, and it was found to be a member of the alphaproteobacteria related to the rickettsiales: in this study, the ca ...	2002	12450827
the cxc chemokine murine monokine induced by ifn-gamma (cxc chemokine ligand 9) is made by apcs, targets lymphocytes including activated b cells, and supports antibody responses to a bacterial pathogen in vivo.	monokine induced by ifn-gamma (mig; cxc chemokine ligand 9) is an ifn-gamma-inducible cxc chemokine that signals through the receptor cxcr3 and is known to function as a chemotactic factor for human t cells, particularly following t cell activation. the mig gene can be induced in multiple cell types and organs, and mig has been shown to contribute to t cell infiltration into immune/inflammatory reactions in peripheral tissues in mice. we have investigated the expression and activities of mig and ...	2002	12133969
tularemia and q fever.	the zoonotic infections caused by francisella tularensis and coxiella burnetii, tularemia and q fever, respectively, are two less commonly encountered clinical illnesses that are becoming increasingly recognized as epidemiologically important human diseases. the prevalence of tularemia and q fever can be positively impacted by increased awareness of the clinical entities that arise from infection by these arthropod-borne organisms. improved recognition of these clinical syndromes will lead to gr ...	2002	11982309
[tularemia as a biological weapon].	tularemia is a zoonosis, caused by the gram-negative bacterium, francisella tularensis. the organism penetrates the human body through interrupted skin or mucous membranes, via animal contact or bites from ticks, deer-flies and mosquitoes. contaminated aerosol and water are alternative modes of transmitting the germ through the respiratory and alimentary tracks. in light of its high infectivity in aerosol and its offensive occupation in the past, tularemia may appear in a biological warfare cont ...	2002	12170560
the 2000 tularemia outbreak: a case-control study of risk factors in disease-endemic and emergent areas, sweden.	a widespread outbreak of tularemia in sweden in 2000 was investigated in a case-control study in which 270 reported cases of tularemia were compared with 438 controls. the outbreak affected parts of sweden where tularemia had hitherto been rare, and these "emergent" areas were compared with the disease-endemic areas. multivariate regression analysis showed mosquito bites to be the main risk factor, with an odds ratio (or) of 8.8. other risk factors were owning a cat (or 2.5) and farm work (or 3. ...	2002	12194773
a procedure for differentiating between the intentional release of biological warfare agents and natural outbreaks of disease: its use in analyzing the tularemia outbreak in kosovo in 1999 and 2000.	the events of 11 september and the subsequent anthrax outbreaks in the usa have opened the world's eyes to the threat posed by terrorist groups, criminal organizations and lone operators who will stop at nothing to achieve their goals. the open or covert use of pathogens and toxins as biological warfare agents can no longer be ruled out. against this background, the appearance of an unusual disease must be studied in order to clarify whether it is a natural or artificially caused occurrence. thi ...	2002	12197873
problems associated with potential massive use of antimicrobial agents as prophylaxis or therapy of a bioterrorist attack.	in addition to the direct sanitary damage of a terrorist attack caused by biological weapons, the consequences of the massive stockpiling and consumption of antimicrobial agents in order to treat or prevent the disease under a potential epidemic due to pathogenic bacteria must also be considered. bacillus anthracis, francisella tularensis and yersinia pestis are the bacteria most likely to be used as terrorist weapons. tetracyclines, quinolones and aminoglycoside are the antibiotics of choice ag ...	2002	12197876
[germs employed as biological weapons].		2002	12215940