Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| vaccination with an attenuated strain of francisella novicida prevents t-cell depletion and protects mice infected with the wild-type strain from severe sepsis. | francisella tularensis is the causative agent of zoonotic tularemia, a severe pneumonia in humans, and francisella novicida causes a similarly severe tularemia in mice upon inhalation. the correlates of protective immunity, as well as the virulence mechanisms of this deadly pathogen, are not well understood. in the present study, we compared the host immune responses of lethally infected and vaccinated mice to highlight the host determinants of protection from this disease. intranasal infection ... | 2009 | 19635830 |
| vaccination with a defined francisella tularensis subsp. novicida pathogenicity island mutant (deltaiglb) induces protective immunity against homotypic and heterotypic challenge. | francisella tularensis, an intracellular gram-negative bacterium, is the causative agent of tularemia and a potential bioweapon. currently, there is no licensed vaccine against this organism. we have characterized the efficacy of a defined f. tularensis subsp. novicida mutant (deltaiglb) as a live attenuated vaccine against pneumonic tularemia. replication of the iglb mutant (kkf235) in murine macrophages was significantly lower than the wild type novicida strain u112, and exhibited an ld(50) gr ... | 2009 | 19651173 |
| the 58-kilodalton major virulence factor of francisella tularensis is required for efficient utilization of iron. | we investigated the role of the 58-kda ftt0918 protein in the iron metabolism of francisella tularensis. the phenotypes of schu s4, a prototypic strain of f. tularensis subsp. tularensis, and the delta ftt0918 and delta fsla isogenic mutants were analyzed. the gene product missing in the delta fsla mutant is responsible for synthesis of a siderophore. when grown in broth with various iron concentrations, the two deletion mutants generally reached lower maximal densities than schu s4. the delta f ... | 2009 | 19651867 |
| diversity of francisella species in environmental samples from martha's vineyard, massachusetts. | we determined whether francisella spp. are present in water, sediment, and soil from an active tularemia natural focus on martha's vineyard, massachusetts, during a multiyear outbreak of pneumonic tularemia. environmental samples were tested by polymerase chain reaction (pcr) targeting francisella species 16s rrna gene and succinate dehydrogenase a (sdha) sequences; evidence of the agent of tularemia was sought by amplification of francisella tularensis-specific sequences for the insertion eleme ... | 2010 | 19669828 |
| diversity of francisella species in environmental samples from martha's vineyard, massachusetts. | we determined whether francisella spp. are present in water, sediment, and soil from an active tularemia natural focus on martha's vineyard, massachusetts, during a multiyear outbreak of pneumonic tularemia. environmental samples were tested by polymerase chain reaction (pcr) targeting francisella species 16s rrna gene and succinate dehydrogenase a (sdha) sequences; evidence of the agent of tularemia was sought by amplification of francisella tularensis-specific sequences for the insertion eleme ... | 2010 | 19669828 |
| replacement of lipopolysaccharide with free lipid a molecules in escherichia coli mutants lacking all core sugars. | escherichia coli mutants deficient in 2-keto-3-deoxy-d-manno-octulosonic acid (kdo) biosynthesis are conditionally lethal, but their phenotypes are bypassed by certain suppressor mutations or by overexpression of msba, the inner membrane flippase for core-lipid a. these strains grow on broth with the tetraacylated precursor lipid iv(a) replacing lipopolysaccharide [meredith, t. c., et al. (2006) acs chem. biol. 1, 33-42]. deletion of kdta, which encodes the kdo transferase, is possible under the ... | 2009 | 19754149 |
| differentiation of gram-negative bacterial aerosol exposure using detected markers in bronchial-alveolar lavage fluid. | the identification of biosignatures of aerosol exposure to pathogens has the potential to provide useful diagnostic information. in particular, markers of exposure to different types of respiratory pathogens may yield diverse sets of markers that can be used to differentiate exposure. we examine a mouse model of aerosol exposure to known gram negative bacterial pathogens, francisella tularensis novicida and pseudomonas aeruginosa. mice were subjected to either a pathogen or control exposure and ... | 2009 | 19756149 |
| 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 ... | 2009 | 19762448 |
| francisella novicida forms in vitro biofilms mediated by an orphan response regulator. | francisella tularensis is associated with water and waterways and infects many species of animals, insects, and protists. the mechanism francisella utilizes to persist in the environment and in tick vectors is currently unknown. we have demonstrated for the first time that francisella novicida, a model organism of f. tularensis, forms a biofilm in vitro. selected f. novicida transposon mutants were tested for their ability to form biofilm compared to the wildtype f. novicida strain. mutation of ... | 2010 | 19763680 |
| description of francisella hispaniensis sp. nov., isolated from human blood, reclassification of francisella novicida (larson et al. 1955) olsufiev et al. 1959 as francisella tularensis subsp. novicida comb. nov. and emended description of the genus francisella. | strain fhsp1t, isolated from human blood in spain in 2003, was studied for its taxonomic allocation. by 16s rrna and reca gene sequencing, the strain was shown to belong to the genus francisella. in the 16s rrna gene sequence, francisella sp. fhsp1t shared similarity of more than 99% with strains of francisella tularensis subspecies and francisella novicida u112t, 98% with francisella piscicida gm2212t and 98.4% with francisella philomiragia atcc 25015t. in the reca gene sequence, francisella sp ... | 2010 | 19783615 |
| francisella tularensis novicida proteomic and transcriptomic data integration and annotation based on semantic web technologies. | this paper summarises the lessons and experiences gained from a case study of the application of semantic web technologies to the integration of data from the bacterial species francisella tularensis novicida (fn). fn data sources are disparate and heterogeneous, as multiple laboratories across the world, using multiple technologies, perform experiments to understand the mechanism of virulence. it is hard to integrate these data sources in a flexible manner that allows new experimental data to b ... | 2009 | 19796400 |
| nemesys: a biological resource for narrowing the gap between sequence and function in the human pathogen neisseria meningitidis. | genome sequences, now available for most pathogens, hold promise for the rational design of new therapies. however, biological resources for genome-scale identification of gene function (notably genes involved in pathogenesis) and/or genes essential for cell viability, which are necessary to achieve this goal, are often sorely lacking. this holds true for neisseria meningitidis, one of the most feared human bacterial pathogens that causes meningitis and septicemia. | 2009 | 19818133 |
| a subset of the diverse cog0523 family of putative metal chaperones is linked to zinc homeostasis in all kingdoms of life. | cog0523 proteins are, like the nickel chaperones of the ureg family, part of the g3e family of gtpases linking them to metallocenter biosynthesis. even though the first cog0523-encoding gene, cobw, was identified almost 20 years ago, little is known concerning the function of other members belonging to this ubiquitous family. | 2009 | 19822009 |
| crystal structures of the histidine acid phosphatase from francisella tularensis provide insight into substrate recognition. | histidine acid phosphatases catalyze the transfer of a phosphoryl group from phosphomonoesters to water at acidic ph using an active-site histidine. the histidine acid phosphatase from the category a pathogen francisella tularensis (fthap) has been implicated in intramacrophage survival and virulence, motivating interest in understanding the structure and mechanism of this enzyme. here, we report a structure-based study of ligand recognition by fthap. the 1.70-a-resolution structure of fthap com ... | 2009 | 19836403 |
| acid phosphatases do not contribute to the pathogenesis of type a francisella tularensis. | the intracellular pathogen francisella tularensis is the causative agent of tularemia, a zoonosis that can affect humans with potentially lethal consequences. essential to francisella virulence is its ability to survive and proliferate within phagocytes through phagosomal escape and cytosolic replication. francisella spp. encode a variety of acid phosphatases, whose roles in phagosomal escape and virulence have been documented yet remain controversial. here we have examined in the highly virulen ... | 2010 | 19858304 |
| acid phosphatases do not contribute to the pathogenesis of type a francisella tularensis. | the intracellular pathogen francisella tularensis is the causative agent of tularemia, a zoonosis that can affect humans with potentially lethal consequences. essential to francisella virulence is its ability to survive and proliferate within phagocytes through phagosomal escape and cytosolic replication. francisella spp. encode a variety of acid phosphatases, whose roles in phagosomal escape and virulence have been documented yet remain controversial. here we have examined in the highly virulen ... | 2010 | 19858304 |
| francisella tularensis subsp. novicida isolated from a human in arizona. | francisella tularensis is the etiologic agent of tularemia and is classified as a select agent by the centers for disease control and prevention. currently four known subspecies of f. tularensis that differ in virulence and geographical distribution are recognized:tularensis (type a), holarctica (type b), mediasiatica, and novicida. because of the select agent status and differences in virulence and geographical location, the molecular analysis of any clinical case of tularemia is of particular ... | 2009 | 19895698 |
| gallium disrupts iron uptake by intracellular and extracellular francisella strains and exhibits therapeutic efficacy in a murine pulmonary infection model. | francisella tularensis requires iron (fe) for growth, but the biologic sources of fe for this organism are largely unknown. we found that francisella sp. growing in broth culture or within human macrophages can acquire fe from the two major host fe-binding proteins, lactoferrin (lf) and transferrin (tf). fe acquisition is a potential target for novel therapies. gallium (ga) is a transition metal that interferes with cellular fe metabolism by competing with fe for uptake/utilization. growth of ei ... | 2010 | 19917753 |
| gallium disrupts iron uptake by intracellular and extracellular francisella strains and exhibits therapeutic efficacy in a murine pulmonary infection model. | francisella tularensis requires iron (fe) for growth, but the biologic sources of fe for this organism are largely unknown. we found that francisella sp. growing in broth culture or within human macrophages can acquire fe from the two major host fe-binding proteins, lactoferrin (lf) and transferrin (tf). fe acquisition is a potential target for novel therapies. gallium (ga) is a transition metal that interferes with cellular fe metabolism by competing with fe for uptake/utilization. growth of ei ... | 2010 | 19917753 |
| computational prediction of essential genes in an unculturable endosymbiotic bacterium, wolbachia of brugia malayi. | wolbachia (wbm) is an obligate endosymbiotic bacterium of brugia malayi, a parasitic filarial nematode of humans and one of the causative agents of lymphatic filariasis. there is a pressing need for new drugs against filarial parasites, such as b. malayi. as wbm is required for b. malayi development and fertility, targeting wbm is a promising approach. however, the lifecycle of neither b. malayi nor wbm can be maintained in vitro. to facilitate selection of potential drug targets we computationa ... | 2009 | 19943957 |
| working toward the future: insights into francisella tularensis pathogenesis and vaccine development. | francisella tularensis is a facultative intracellular gram-negative pathogen and the etiological agent of the zoonotic disease tularemia. recent advances in the field of francisella genetics have led to a rapid increase in both the generation and subsequent characterization of mutant strains exhibiting altered growth and/or virulence characteristics within various model systems of infection. in this review, we summarize the major properties of several francisella species, including f. tularensis ... | 2009 | 19946137 |
| contributions of francisella tularensis subsp. novicida chitinases and sec secretion system to biofilm formation on chitin. | francisella tularensis, the zoonotic cause of tularemia, can infect numerous mammals and other eukaryotes. although studying f. tularensis pathogenesis is essential to comprehending disease, mammalian infection is just one step in the ecology of francisella species. f. tularensis has been isolated from aquatic environments and arthropod vectors, environments in which chitin could serve as a potential carbon source and as a surface for attachment and growth. we show that f. tularensis subsp. novi ... | 2010 | 19948864 |
| eradication of intracellular francisella tularensis in thp-1 human macrophages with a novel autophagy inducing agent. | autophagy has been shown recently to play an important role in the intracellular survival of several pathogenic bacteria. in this study, we investigated the effect of a novel small-molecule autophagy-inducing agent, ar-12, on the survival of francisella tularensis, the causative bacterium of tularemia in humans and a potential bioterrorism agent, in macrophages. | 2009 | 20003180 |
| francisella tularensis t-cell antigen identification using humanized hla-dr4 transgenic mice. | there is no licensed vaccine against the intracellular pathogen francisella tularensis. the use of conventional mouse strains to screen protective vaccine antigens may be problematic, given the differences in the major histocompatibility complex (mhc) binding properties between murine and human antigen-presenting cells. we used engineered humanized mice that lack endogenous mhc class ii alleles but that express a human hla allele (hla-dr4 transgenic [tg] mice) to identify potential subunit vacci ... | 2010 | 20016043 |
| francisella tularensis t-cell antigen identification using humanized hla-dr4 transgenic mice. | there is no licensed vaccine against the intracellular pathogen francisella tularensis. the use of conventional mouse strains to screen protective vaccine antigens may be problematic, given the differences in the major histocompatibility complex (mhc) binding properties between murine and human antigen-presenting cells. we used engineered humanized mice that lack endogenous mhc class ii alleles but that express a human hla allele (hla-dr4 transgenic [tg] mice) to identify potential subunit vacci ... | 2010 | 20016043 |
| differential ability of novel attenuated targeted deletion mutants of francisella tularensis subspecies tularensis strain schu s4 to protect mice against aerosol challenge with virulent bacteria: effects of host background and route of immunization. | francisella tularensis subspecies tularensis is a highly virulent facultative intracellular pathogen of humans and a potential biological weapon. a live vaccine strain, f. tularensis lvs, was developed more than 50 years ago by pragmatic attenuation of a strain of the less virulent holarctica subspecies. lvs was demonstrated to be highly effective in human volunteers who were exposed to intradermal challenge with fully virulent subsp. tularensis, but was less effective against aerosol exposure. ... | 2010 | 20018266 |
| differential ability of novel attenuated targeted deletion mutants of francisella tularensis subspecies tularensis strain schu s4 to protect mice against aerosol challenge with virulent bacteria: effects of host background and route of immunization. | francisella tularensis subspecies tularensis is a highly virulent facultative intracellular pathogen of humans and a potential biological weapon. a live vaccine strain, f. tularensis lvs, was developed more than 50 years ago by pragmatic attenuation of a strain of the less virulent holarctica subspecies. lvs was demonstrated to be highly effective in human volunteers who were exposed to intradermal challenge with fully virulent subsp. tularensis, but was less effective against aerosol exposure. ... | 2010 | 20018266 |
| inhibition of acpa phosphatase activity with ascorbate attenuates francisella tularensis intramacrophage survival. | acid phosphatase activity in the highly infectious intracellular pathogen francisella tularensis is directly related with the ability of these bacteria to survive inside host cells. pharmacological inactivation of acid phosphatases could potentially help in the treatment of tularemia or even be utilized to neutralize the infection. in the present work, we report inhibitory compounds for three of the four major acid phosphatases produced by f. tularensis schu4: acpa, acpb, and acpc. the inhibitor ... | 2010 | 20028980 |
| inhibition of acpa phosphatase activity with ascorbate attenuates francisella tularensis intramacrophage survival. | acid phosphatase activity in the highly infectious intracellular pathogen francisella tularensis is directly related with the ability of these bacteria to survive inside host cells. pharmacological inactivation of acid phosphatases could potentially help in the treatment of tularemia or even be utilized to neutralize the infection. in the present work, we report inhibitory compounds for three of the four major acid phosphatases produced by f. tularensis schu4: acpa, acpb, and acpc. the inhibitor ... | 2010 | 20028980 |
| the francisella tularensis pathogenicity island encodes a secretion system that is required for phagosome escape and virulence. | francisella tularensis causes the human disease tularemia. f. tularensis is able to survive and replicate within macrophages, a trait that has been correlated with its high virulence, but it is unclear the exact mechanism(s) this organism uses to escape killing within this hostile environment. f. tularensis virulence is dependent upon the francisella pathogenicity island (fpi), a cluster of genes that we show here shares homology with type vi secretion gene clusters in vibrio cholerae and pseudo ... | 2009 | 20054881 |
| antibiotic sensitivity profiles determined with an escherichia coli gene knockout collection: generating an antibiotic bar code. | we have defined a sensitivity profile for 22 antibiotics by extending previous work testing the entire keio collection of close to 4,000 single-gene knockouts in escherichia coli for increased susceptibility to 1 of 14 different antibiotics (ciprofloxacin, rifampin [rifampicin], vancomycin, ampicillin, sulfamethoxazole, gentamicin, metronidazole, streptomycin, fusidic acid, tetracycline, chloramphenicol, nitrofurantoin, erythromycin, and triclosan). we screened one or more subinhibitory concentr ... | 2010 | 20065048 |
| stimulator of ifn gene is critical for induction of ifn-beta during chlamydia muridarum infection. | type i ifn signaling has recently been shown to be detrimental to the host during infection with chlamydia muridarum in both mouse lung and female genital tract. however, the pattern recognition receptor and the signaling pathways involved in chlamydial-induced ifn-beta are unclear. previous studies have demonstrated no role for tlr4 and a partial role for myd88 in chlamydial-induced ifn-beta. in this study, we demonstrate that mouse macrophages lacking tlr3, trif, tlr7, or tlr9 individually or ... | 2010 | 20107183 |
| altered lipid a structures and polymyxin hypersensitivity of rhizobium etli mutants lacking the lpxe and lpxf phosphatases. | the lipid a of rhizobium etli, a nitrogen-fixing plant endosymbiont, displays significant structural differences when compared to that of escherichia coli. an especially striking feature of r. etli lipid a is that it lacks both the 1- and 4'-phosphate groups. the 4'-phosphate moiety of the distal glucosamine unit is replaced with a galacturonic acid residue. the dephosphorylated proximal unit is present as a mixture of the glucosamine hemiacetal and an oxidized 2-aminogluconate derivative. disti ... | 2010 | 20153447 |
| immunotherapy markedly increases the effectiveness of antimicrobial therapy for treatment of burkholderia pseudomallei infection. | burkholderia pseudomallei is a soil bacterium that is endemic in southeast asia and northern australia and that can cause both acutely lethal pneumonia and chronic systemic infections in humans. the effective treatment of infection with b. pseudomallei requires rapid diagnosis and prolonged treatment with high doses of antimicrobials, and even with appropriate antibiotic therapy, patient relapses are common. thus, new approaches to the treatment of b. pseudomallei infections are needed. in the p ... | 2010 | 20176901 |
| identification of francisella tularensis by whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry: fast, reliable, robust, and cost-effective differentiation on species and subspecies levels. | francisella tularensis, the causative agent of tularemia, is a potential agent of bioterrorism. the phenotypic discrimination of closely related, but differently virulent, francisella tularensis subspecies with phenotyping methods is difficult and time-consuming, often producing ambiguous results. as a fast and simple alternative, matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) was applied to 50 different strains of the genus francisella to assess its ... | 2010 | 20181907 |
| interferon-inducible p200-family proteins as novel sensors of cytoplasmic dna: role in inflammation and autoimmunity. | deregulated innate immune responses that result in increased levels of type i interferons (ifns) and stimulation of ifn-inducible genes are thought to contribute to chronic inflammation and autoimmunity. one family of ifn-inducible genes is the ifi200 family, which includes the murine (eg, ifi202a, ifi202b, ifi203, ifi204, mndal, and aim2) and human (eg, ifi16, mnda, ifix, and aim2) genes. genes in the family encode structurally related proteins (the p200-family proteins), which share at least o ... | 2010 | 20187776 |
| 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 ... | 2010 | 20231408 |
| francisella acid phosphatases inactivate the nadph oxidase in human phagocytes. | francisella tularensis contains four putative acid phosphatases that are conserved in francisella novicida. an f. novicida quadruple mutant (acpa, acpb, acpc, and hap [deltaabch]) is unable to escape the phagosome or survive in macrophages and is attenuated in the mouse model. we explored whether reduced survival of the deltaabch mutant within phagocytes is related to the oxidative response by human neutrophils and macrophages. f. novicida and f. tularensis subspecies failed to stimulate reactiv ... | 2010 | 20348422 |
| mycoplasma suppression of thp-1 cell tlr responses is corrected with antibiotics. | mycoplasma contamination of cultured cell lines is a serious problem in research, altering cellular response to different stimuli thus compromising experimental results. we found that chronic mycoplasma contamination of thp-1 cells suppresses responses of thp-1 cells to tlr stimuli. for example, e. coli lps induced il-1 beta was suppressed by 6 fold and il-8 by 10 fold in mycoplasma positive thp-1 cells. responses to live f. novicida challenge were suppressed by 50-fold and 40-fold respectively ... | 2010 | 20360862 |
| study of matrix additives for sensitive analysis of lipid a by matrix-assisted laser desorption ionization mass spectrometry. | matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) has been widely used for structural characterization of bacterial endotoxins (lipid a). however, the mass spectrometric behavior of the lipid a molecule is highly dependent on the matrix. furthermore, this dependence is strongly linked to phosphorylation patterns. using lipid a from escherichia coli o116 as a model system, we have investigated the effects of different matrices and comatrix compounds on th ... | 2010 | 20382818 |
| indoleamine 2,3-dioxygenase 1 is a lung-specific innate immune defense mechanism that inhibits growth of francisella tularensis tryptophan auxotrophs. | upon microbial challenge, organs at various anatomic sites of the body employ different innate immune mechanisms to defend against potential infections. accordingly, microbial pathogens evolved to subvert these organ-specific host immune mechanisms to survive and grow in infected organs. francisella tularensis is a bacterium capable of infecting multiple organs and thus encounters a myriad of organ-specific defense mechanisms. this suggests that f. tularensis may possess specific factors that ai ... | 2010 | 20385761 |
| azithromycin effectiveness against intracellular infections of francisella. | macrolide antibiotics are commonly administered for bacterial respiratory illnesses. azithromycin (az) is especially noted for extremely high intracellular concentrations achieved within macrophages which is far greater than the serum concentration. clinical strains of type b francisella (f.) tularensis have been reported to be resistant to az, however our laboratory francisella strains were found to be sensitive. we hypothesized that different strains/species of francisella (including type a) m ... | 2010 | 20416090 |
| differentiation of bacteria using fatty acid profiles from gas chromatography-tandem mass spectrometry. | fatty acids are essential components in cell membranes of bacteria, and they determine the different structures of lipids and lipid a. therefore, fatty acids are good targets for development of rapid and reliable methods for differentiation of bacteria. | 2010 | 20474059 |
| directed screen of francisella novicida virulence determinants using drosophila melanogaster. | francisella tularensis is a highly virulent, facultative intracellular human pathogen whose virulence mechanisms are not well understood. occasional outbreaks of tularemia and the potential use of f. tularensis as a bioterrorist agent warrant better knowledge about the pathogenicity of this bacterium. thus far, genome-wide in vivo screens for virulence factors have been performed in mice, all however restricted by the necessity to apply competition-based, negative-selection assays. we wanted to ... | 2010 | 20479082 |
| molecular bases of proliferation of francisella tularensis in arthropod vectors. | arthropod vectors are important vehicles for transmission of francisella tularensis between mammals, but very little is known about the f. tularensis-arthropod vector interaction. drosophila melanogaster has been recently developed as an arthropod vector model for f. tularensis. we have shown that intracellular trafficking of f. tularensis within human monocytes-derived macrophages and d. melanogaster-derived s2 cells is very similar. within both evolutionarily distant host cells, the francisell ... | 2010 | 20482589 |
| molecular complexity orchestrates modulation of phagosome biogenesis and escape to the cytosol of macrophages by francisella tularensis. | upon entry of francisella tularensis to macrophages, the francisella-containing phagosome (fcp) is trafficked into an acidified late endosome-like phagosome with limited fusion to the lysosomes followed by rapid escape into the cytosol where the organism replicates. although the francisella pathogenicity island (fpi), which encodes a type vi-like secretion apparatus, is required for modulation of phagosome biogenesis and escape into the cytosol, the mechanisms involved are not known. to decipher ... | 2010 | 20482590 |
| francisella tularensis antioxidants harness reactive oxygen species to restrict macrophage signaling and cytokine production. | francisella tularensis is the etiologic agent of the highly infectious animal and human disease tularemia. its extreme infectivity and virulence are associated with its ability to evade immune detection, which we now link to its robust reactive oxygen species-scavenging capacity. infection of primary human monocyte-derived macrophages with virulent f. tularensis schus4 prevented proinflammatory cytokine production in the presence or absence of ifn-gamma compared with infection with the attenuate ... | 2010 | 20558723 |
| cutting edge: cytosolic bacterial dna activates the inflammasome via aim2. | pathogens are detected by pattern recognition receptors that, upon activation, orchestrate an appropriate immune response. the tlrs and the nucleotide-binding oligomerization domain-like receptors (nlrs) are prototypic pattern recognition receptors that detect extracellular and cytosolic pathogens, respectively. listeria monocytogenes has both extracellular and cytosolic phases and is detected in the cytosol by members of the nlr family. these include two nlr members, nlrc4 and nlrp3, that, upon ... | 2010 | 20562263 |
| accurate detection of low levels of fluorescence emission in autofluorescent background: francisella-infected macrophage cells. | cellular autofluorescence, though ubiquitous when imaging cells and tissues, is often assumed to be small in comparison to the signal of interest. uniform estimates of autofluorescence intensity obtained from separate control specimens are commonly employed to correct for autofluorescence. while these may be sufficient for high signal-to-background applications, improvements in detector and probe technologies and introduction of spectral imaging microscopes have increased the sensitivity of fluo ... | 2010 | 20569528 |
| bronchus-associated lymphoid tissue (balt) and survival in a vaccine mouse model of tularemia. | francisella tularensis causes severe pulmonary disease, and nasal vaccination could be the ideal measure to effectively prevent it. nevertheless, the efficacy of this type of vaccine is influenced by the lack of an effective mucosal adjuvant. | 2010 | 20585390 |
| redundant roles for inflammasome receptors nlrp3 and nlrc4 in host defense against salmonella. | intracellular pathogens and endogenous danger signals in the cytosol engage nod-like receptors (nlrs), which assemble inflammasome complexes to activate caspase-1 and promote the release of proinflammatory cytokines il-1beta and il-18. however, the nlrs that respond to microbial pathogens in vivo are poorly defined. we show that the nlrs nlrp3 and nlrc4 both activate caspase-1 in response to salmonella typhimurium. responding to distinct bacterial triggers, nlrp3 and nlrc4 recruited asc and casp ... | 2010 | 20603313 |
| an alternative route for udp-diacylglucosamine hydrolysis in bacterial lipid a biosynthesis. | the outer leaflet of the outer membranes of gram-negative bacteria is composed primarily of lipid a, the hydrophobic anchor of lipopolysaccharide. like escherichia coli, most gram-negative bacteria encode one copy of each of the nine genes required for lipid a biosynthesis. an important exception exists in the case of the fourth enzyme, lpxh, a peripheral membrane protein that hydrolyzes udp-2,3-diacylglucosamine to form 2,3-diacylglucosamine 1-phosphate and ump by catalyzing the attack of water ... | 2010 | 20608695 |
| multiple mechanisms of nadph oxidase inhibition by type a and type b francisella tularensis. | ft is a facultative intracellular pathogen that infects many cell types, including neutrophils. in previous work, we demonstrated that the type b ft strain lvs disrupts nadph oxidase activity throughout human neutrophils, but how this is achieved is incompletely defined. here, we used several type a and type b strains to demonstrate that ft-mediated nadph oxidase inhibition is more complex than appreciated previously. we confirm that phagosomes containing ft opsonized with as exclude flavocytoch ... | 2010 | 20610796 |
| construction of a bioluminescence reporter plasmid for francisella tularensis. | a francisella tularensis shuttle vector that constitutively expresses the photorhabdus luminescens lux operon in type a and type b strains of f. tularensis was constructed. the bioluminescence reporter plasmid was introduced into the live vaccine strain of f. tularensis and used to follow f. tularensis growth in a murine intranasal challenge model in real-time by bioluminescence imaging. the results show that the new bioluminescence reporter plasmid represents a useful tool for tularemia researc ... | 2010 | 20620161 |
| porphyromonas gingivalis resistance to polymyxin b is determined by the lipid a 4'-phosphatase, pgn_0524. | to elucidate the genetic basis for the pronounced resistance that the oral pathogen, porphyromonas gingivalis (p. gingivalis), exhibits towards the cationic antimicrobial peptide, polymyxin b. | 2009 | 20657724 |
| removal of the outer kdo from helicobacter pylori lipopolysaccharide and its impact on the bacterial surface. | helicobacter pylori produces a unique surface lipopolysaccharide (lps) characterized by strikingly low endotoxicity that is thought to aid the organism in evading the host immune response. this reduction in endotoxicity is predicted to arise from the modification of the kdo-lipid a domain of helicobacter lps by a series of membrane bound enzymes including a kdo (3-deoxy-d-manno-octulosonic acid) hydrolase responsible for the modification of the core oligosaccharide. here, we report that kdo hydr ... | 2010 | 20659292 |
| a two-component kdo hydrolase in the inner membrane of francisella novicida. | lipid a coats the outer surface of the outer membrane of gram-negative bacteria. in francisella tularensis subspecies novicida lipid a is present either as the covalently attached anchor of lipopolysaccharide (lps) or as free lipid a. the lipid a moiety of francisella lps is linked to the core domain by a single 2-keto-3-deoxy-d-manno-octulosonic acid (kdo) residue. f. novicida kdta is bi-functional, but f. novicida contains a membrane-bound kdo hydrolase that removes the outer kdo unit. the hyd ... | 2010 | 20662782 |
| mutations of francisella novicida that alter the mechanism of its phagocytosis by murine macrophages. | infection with the bacterial pathogen francisella tularensis tularensis (f. tularensis) causes tularemia, a serious and debilitating disease. francisella tularensis novicida strain u112 (abbreviated f. novicida), which is closely related to f. tularensis, is pathogenic for mice but not for man, making it an ideal model system for tularemia. intracellular pathogens like francisella inhibit the innate immune response, thereby avoiding immune recognition and death of the infected cell. because acti ... | 2010 | 20686600 |
| objections to the transfer of francisella novicida to the subspecies rank of francisella tularensis. | 2010 | 20688748 | |
| objections to the transfer of francisella novicida to the subspecies rank of francisella tularensis - response to johansson et al. | 2010 | 20688749 | |
| detection of francisella tularensis in alaskan mosquitoes (diptera: culicidae) and assessment of a laboratory model for transmission. | tularemia is a zoonotic disease caused by the category a bioterrorism agent francisella tularensis. in scandinavia, tularemia transmission by mosquitoes has been widely cited in the literature. we tested >2,500 mosquitoes captured in alaska and found francisella dna in 30% of pooled samples. to examine the potential for transmission of francisella by mosquitoes, we developed a mosquito model of francisella infection. larvae of anopheles gambiae giles and aedes aegypti (l.) readily ingest f. tula ... | 2010 | 20695280 |
| bcskc is an essential protein for the type vi secretion system activity in burkholderia cenocepacia that forms an outer membrane complex with bcslb. | the type vi secretion system (t6ss) contributes to the virulence of burkholderia cenocepacia, an opportunistic pathogen causing serious chronic infections in patients with cystic fibrosis. bcsk(c) is a highly conserved protein among the t6sss in gram-negative bacteria. here, we show that bcsk(c) is required for hcp secretion and cytoskeletal redistribution in macrophages upon bacterial infection. these two phenotypes are associated with a functional t6ss in b. cenocepacia. experiments employing ... | 2010 | 20729192 |
| escherichia coli mutants that synthesize dephosphorylated lipid a molecules. | the lipid a moiety of escherichia coli lipopolysaccharide is a hexaacylated disaccharide of glucosamine that is phosphorylated at the 1 and 4' positions. expression of the francisella novicida lipid a 1-phosphatase fnlpxe in e. coli results in dephosphorylation of the lipid a proximal unit. coexpression of fnlpxe and the rhizobium leguminosarum lipid a oxidase rllpxq in e. coli converts much of the proximal glucosamine to 2-amino-2-deoxygluconate. expression of the f. novicida lipid a 4'-phospha ... | 2010 | 20795687 |
| 3-deoxy-d-manno-octulosonic acid (kdo) hydrolase identified in francisella tularensis, helicobacter pylori, and legionella pneumophila. | 3-deoxy-d-manno-octulosonic acid (kdo) is an eight-carbon sugar ubiquitous in gram-negative bacterial lipopolysaccharides (lps). although its biosynthesis is well described, no protein has yet been identified as a kdo hydrolase. however, kdo hydrolase enzymatic activity has been detected in membranes of helicobacter pylori and francisella tularensis and may be responsible for the removal of side-chain kdo from the lps core saccharides. we now report the identification of genes encoding a kdo hyd ... | 2010 | 20801884 |
| abc transporters involved in export of cell surface glycoconjugates. | complex glycoconjugates play critical roles in the biology of microorganisms. despite the remarkable diversity in glycan structures and the bacteria that produce them, conserved themes are evident in the biosynthesis-export pathways. one of the primary pathways involves representatives of the atp-binding cassette (abc) transporter superfamily. these proteins are responsible for the export of a wide variety of cell surface oligo- and polysaccharides in both gram-positive and gram-negative bacteri ... | 2010 | 20805402 |
| combined statistical analyses of peptide intensities and peptide occurrences improves identification of significant peptides from ms-based proteomics data. | liquid chromatography-mass spectrometry-based (lc-ms) proteomics uses peak intensities of proteolytic peptides to infer the differential abundance of peptides/proteins. however, substantial run-to-run variability in intensities and observations (presence/absence) of peptides makes data analysis quite challenging. the missing observations in lc-ms proteomics data are difficult to address with traditional imputation-based approaches because the mechanisms by which data are missing are unknown a pr ... | 2010 | 20831241 |
| mast cell/il-4 control of francisella tularensis replication and host cell death is associated with increased atp production and phagosomal acidification. | mast cells are now recognized as effective modulators of innate immunity. we recently reported that mast cells and secreted interleukin-4 (il-4) effectively control intramacrophage replication of francisella tularensis live vaccine strain (lvs), and that mice deficient in mast cells or il-4 receptor (il-4r(-/-)) exhibit greater susceptibility to pulmonary challenge. in this study, we further evaluated the mechanism(s) by which mast cells/il-4 control intramacrophage bacterial replication and hos ... | 2011 | 20861832 |
| mast cell/il-4 control of francisella tularensis replication and host cell death is associated with increased atp production and phagosomal acidification. | mast cells are now recognized as effective modulators of innate immunity. we recently reported that mast cells and secreted interleukin-4 (il-4) effectively control intramacrophage replication of francisella tularensis live vaccine strain (lvs), and that mice deficient in mast cells or il-4 receptor (il-4r(-/-)) exhibit greater susceptibility to pulmonary challenge. in this study, we further evaluated the mechanism(s) by which mast cells/il-4 control intramacrophage bacterial replication and hos ... | 2011 | 20861832 |
| reciprocal analysis of francisella novicida infections of a drosophila melanogaster model reveal host-pathogen conflicts mediated by reactive oxygen and imd-regulated innate immune response. | the survival of a bacterial pathogen within a host depends upon its ability to outmaneuver the host immune response. thus, mutant pathogens provide a useful tool for dissecting host-pathogen relationships, as the strategies the microbe has evolved to counteract immunity reveal a host's immune mechanisms. in this study, we examined the pathogen francisella novicida and identified new bacterial virulence factors that interact with different parts of the drosophila melanogaster innate immune system ... | 2010 | 20865166 |
| burkholderia type vi secretion systems have distinct roles in eukaryotic and bacterial cell interactions. | bacteria that live in the environment have evolved pathways specialized to defend against eukaryotic organisms or other bacteria. in this manuscript, we systematically examined the role of the five type vi secretion systems (t6sss) of burkholderia thailandensis (b. thai) in eukaryotic and bacterial cell interactions. consistent with phylogenetic analyses comparing the distribution of the b. thai t6sss with well-characterized bacterial and eukaryotic cell-targeting t6sss, we found that t6ss-5 pla ... | 2010 | 20865170 |
| structure of an essential bacterial protein yeaz (tm0874) from thermotoga maritima at 2.5 å resolution. | yeaz is involved in a protein network that is essential for bacteria. the crystal structure of yeaz from thermotoga maritima was determined to 2.5 å resolution. although this protein belongs to a family of ancient actin-like atpases, it appears that it has lost the ability to bind atp since it lacks some key structural features that are important for interaction with atp. a conserved surface was identified, supporting its role in the formation of protein complexes. | 2010 | 20944216 |
| structure of an essential bacterial protein yeaz (tm0874) from thermotoga maritima at 2.5 å resolution. | yeaz is involved in a protein network that is essential for bacteria. the crystal structure of yeaz from thermotoga maritima was determined to 2.5 å resolution. although this protein belongs to a family of ancient actin-like atpases, it appears that it has lost the ability to bind atp since it lacks some key structural features that are important for interaction with atp. a conserved surface was identified, supporting its role in the formation of protein complexes. | 2010 | 20944216 |
| deciphering the intracellular metabolism of listeria monocytogenes by mutant screening and modelling. | the human pathogen listeria monocytogenes resides and proliferates within the cytoplasm of epithelial cells. while the virulence factors essentially contributing to this step of the infection cycle are well characterized, the set of listerial genes contributing to intracellular replication remains to be defined on a genome-wide level. | 2010 | 20955543 |
| the lipid a phosphate position determines differential host toll-like receptor 4 responses to phylogenetically related symbiotic and pathogenic bacteria. | the human symbiont bacteroides thetaiotaomicron promotes intestinal function and health, whereas the phylogenetically related pathogen porphyromonas gingivalis is associated with the chronic oral inflammatory disease periodontitis. although both b. thetaiotaomicron and p. gingivalis synthesize lipopolysaccharides (lps) consisting of penta-acylated, monophosphorylated lipid a in addition to immunologically silent, nonphosphorylated lipid a, they elicit strikingly distinct toll-like receptor 4 (tl ... | 2010 | 20974832 |
| the lipid a phosphate position determines differential host toll-like receptor 4 responses to phylogenetically related symbiotic and pathogenic bacteria. | the human symbiont bacteroides thetaiotaomicron promotes intestinal function and health, whereas the phylogenetically related pathogen porphyromonas gingivalis is associated with the chronic oral inflammatory disease periodontitis. although both b. thetaiotaomicron and p. gingivalis synthesize lipopolysaccharides (lps) consisting of penta-acylated, monophosphorylated lipid a in addition to immunologically silent, nonphosphorylated lipid a, they elicit strikingly distinct toll-like receptor 4 (tl ... | 2010 | 20974832 |
| identification and modeling of a drug target for clostridium perfringens sm101. | in the present study, comparative genome analysis between clostridium perfringens and the human genome was carried out to identify genes that are essential for the pathogen's survival, and non-homologous to the genes of human host, that can be used as potential drug targets. the study resulted in the identification of 426 such genes. the number of these potential drug targets thus identified is significantly lower than the genome's protein coding capacity (2558 protein coding genes). the 426 gen ... | 2010 | 20978600 |
| up-regulation of microrna-155 in macrophages contributes to increased tumor necrosis factor {alpha} (tnf{alpha}) production via increased mrna half-life in alcoholic liver disease. | activation of kupffer cells (kcs) by gut-derived lipopolysaccharide (lps) and toll-like receptors 4 (tlr4)-lps-mediated increase in tnfα production has a central role in the pathogenesis of alcoholic liver disease. micro-rna (mir)-125b, mir-146a, and mir-155 can regulate inflammatory responses to lps. here we evaluated the involvement of mirs in alcohol-induced macrophage activation. chronic alcohol treatment in vitro resulted in a time-dependent increase in mir-155 but not mir-125b or mir-146a ... | 2010 | 21062749 |
| up-regulation of microrna-155 in macrophages contributes to increased tumor necrosis factor {alpha} (tnf{alpha}) production via increased mrna half-life in alcoholic liver disease. | activation of kupffer cells (kcs) by gut-derived lipopolysaccharide (lps) and toll-like receptors 4 (tlr4)-lps-mediated increase in tnfα production has a central role in the pathogenesis of alcoholic liver disease. micro-rna (mir)-125b, mir-146a, and mir-155 can regulate inflammatory responses to lps. here we evaluated the involvement of mirs in alcohol-induced macrophage activation. chronic alcohol treatment in vitro resulted in a time-dependent increase in mir-155 but not mir-125b or mir-146a ... | 2010 | 21062749 |
| francisella tularensis schu s4 o-antigen and capsule biosynthesis gene mutants induce early cell death in human macrophages. | francisella tularensis is capable of rampant intracellular growth and causes a potentially fatal disease in humans. whereas many mutational studies have been performed with avirulent strains of francisella, relatively little has been done with strains that cause human disease. we generated a near-saturating transposon library in the virulent strain schu s4, which was subjected to high-throughput screening by transposon site hybridization through primary human macrophages, negatively selecting 20 ... | 2010 | 21078861 |
| francisella tularensis schu s4 o-antigen and capsule biosynthesis gene mutants induce early cell death in human macrophages. | francisella tularensis is capable of rampant intracellular growth and causes a potentially fatal disease in humans. whereas many mutational studies have been performed with avirulent strains of francisella, relatively little has been done with strains that cause human disease. we generated a near-saturating transposon library in the virulent strain schu s4, which was subjected to high-throughput screening by transposon site hybridization through primary human macrophages, negatively selecting 20 ... | 2010 | 21078861 |
| evolution of the kdo2-lipid a biosynthesis in bacteria. | lipid a is the highly immunoreactive endotoxic center of lipopolysaccharide (lps). it anchors the lps into the outer membrane of most gram-negative bacteria. lipid a can be recognized by animal cells, triggers defense-related responses, and causes gram-negative sepsis. the biosynthesis of kdo2-lipid a, the lps substructure, involves with nine enzymatic steps. | 2010 | 21106097 |
| attenuated response of aged mice to respiratory francisella novicida is characterized by reduced cell death and absence of subsequent hypercytokinemia. | pneumonia and pulmonary infections are major causes of mortality among the growing elderly population. age associated attenuations of various immune parameters, involved with both innate and adaptive responses are collectively known as immune senescence. these changes are likely to be involved with differences in host susceptibility to disease between young and aged individuals. | 2010 | 21124895 |
| proteomic characterization and functional analysis of outer membrane vesicles of francisella novicida suggests possible role in virulence and use as a vaccine. | we have isolated and characterized outer membrane vesicles (omvs) from francisella. transport of effector molecules through secretion systems is a major mechanism by which francisella tularensis alters the extracellular proteome and interacts with the host during infection. outer membrane vesicles produced by francisella were examined using tem and afm and found to be 43-125 nm in size, representing another potential mechanism for altering the extracellular environment. a proteomic analysis (lc- ... | 2011 | 21138299 |
| cloning, expression, purification, crystallization and preliminary x-ray diffraction analysis of intracellular growth locus e (igle) protein from francisella tularensis subsp. novicida. | tularaemia is an uncommon but potentially dangerous zoonotic disease caused by the bacterium francisella tularensis. as few as ten bacterial cells are sufficient to cause disease in a healthy human, making this one of the most infectious disease agents known. the virulence of this organism is dependent upon a genetic locus known as the francisella pathogenicity island (fpi), which encodes components of a secretion system that is related to the type vi secretion system. here, the cloning, express ... | 2010 | 21139203 |
| differential requirement for caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing. | activation of the cysteine protease caspase-1 is a key event in the innate immune response to infections. synthesized as a proprotein, caspase-1 undergoes autoproteolysis within multiprotein complexes called inflammasomes. activated caspase-1 is required for proteolytic processing and for release of the cytokines interleukin-1β and interleukin-18, and it can also cause rapid macrophage cell death. we show that macrophage cell death and cytokine maturation in response to infection with diverse ba ... | 2010 | 21147462 |
| preservation of viable francisella tularensis for forensic analysis. | as a preservation solution, (1%) ammonium chloride may be preferred over other conventionally used storage solutions because of its compatibility with analytical techniques such as mass spectrometry. in this study, ammonium chloride performed as well or better than phosphate buffered saline with tween or butterfields/tween for preserving francisella tularensis subsp. novicida. | 2010 | 21167882 |
| phenotypic landscape of a bacterial cell. | the explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. using e. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover ... | 2010 | 21185072 |
| phenotypic landscape of a bacterial cell. | the explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. using e. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover ... | 2010 | 21185072 |
| evolution of bacterial phosphoglycerate mutases: non-homologous isofunctional enzymes undergoing gene losses, gains and lateral transfers. | the glycolytic phosphoglycerate mutases exist as non-homologous isofunctional enzymes (nise) having independent evolutionary origins and no similarity in primary sequence, 3d structure, or catalytic mechanism. cofactor-dependent pgm (dpgm) requires 2,3-bisphosphoglycerate for activity; cofactor-independent pgm (ipgm) does not. the pgm profile of any given bacterium is unpredictable and some organisms such as escherichia coli encode both forms. | 2010 | 21187861 |
| identification of t-cell epitopes in francisella tularensis using an ordered protein array of serological targets. | francisella tularensis is a gram-negative intracellular bacterium that is the causative agent of tularaemia. concerns regarding its use as a bioterrorism agent have led to a renewed interest in the biology of infection, host response and pathogenesis. a robust t-cell response is critical to confer protection against f. tularensis. however, characterization of the cellular immune response has been hindered by the paucity of tools to examine the anti-francisella immune response at the molecular le ... | 2011 | 21214540 |
| polymicrobial infection with periodontal pathogens specifically enhances microrna mir-146a in apoe-/- mice during experimental periodontal disease. | porphyromonas gingivalis, treponema denticola, and tannerella forsythia are periodontal pathogens associated with the etiology of adult periodontitis as polymicrobial infections. recent studies demonstrated that oral infection with p. gingivalis induces both periodontal disease and atherosclerosis in hyperlipidemic and proatherogenic apoe(-/-) mice. in this study, we explored the expression of micrornas (mirnas) in maxillas (periodontium) and spleens isolated from apoe(-/-) mice infected with p. ... | 2011 | 21263019 |
| mining high-throughput experimental data to link gene and function. | nearly 2200 genomes that encode around 6 million proteins have now been sequenced. around 40% of these proteins are of unknown function, even when function is loosely and minimally defined as 'belonging to a superfamily'. in addition to in silico methods, the swelling stream of high-throughput experimental data can give valuable clues for linking these unknowns with precise biological roles. the goal is to develop integrative data-mining platforms that allow the scientific community at large to ... | 2011 | 21310501 |
| stress response regulators identified through genome-wide transcriptome analysis of the (p)ppgpp-dependent response in rhizobium etli. | abstract: background: the alarmone (p)ppgpp mediates a global reprogramming of gene expression upon nutrient limitation and other stresses to cope with these unfavorable conditions. synthesis of (p)ppgpp is, in most bacteria, controlled by rela/spot (rsh) proteins. the role of (p)ppgpp has been characterized primarily in escherichia coli and several gram-positive bacteria. here, we report the first in-depth analysis of the (p)ppgpp-regulon in an a-proteobacterium using a high-resolution tiling a ... | 2011 | 21324192 |
| the origin of a derived superkingdom: how a gram-positive bacterium crossed the desert to become an archaeon. | the tree of life is usually rooted between archaea and bacteria. we have previously presented three arguments that support placing the root of the tree of life in bacteria. the data have been dismissed because those who support the canonical rooting between the prokaryotic superkingdoms cannot imagine how the vast divide between the prokaryotic superkingdoms could be crossed. | 2011 | 21356104 |
| phagocytic receptors dictate phagosomal escape and intracellular proliferation of francisella tularensis. | francisella tularensis, the causative agent of tularemia, survives and proliferates within macrophages of the infected host as part of its pathogenic strategy, through an intracellular life cycle that includes phagosomal escape and extensive proliferation within the macrophage cytosol. various in vitro models of francisella-macrophage interactions have been developed, using either opsonic or nonopsonic phagocytosis, and have generated discrepant results on the timing and extent of francisella ph ... | 2011 | 21422184 |
| features of sepsis caused by pulmonary infection with francisella tularensis type a strain. | the virulence mechanisms of francisella tularensis, the causative agent of severe pneumonia in humans and a cdc category a bioterrorism agent, are not fully defined. as sepsis is the leading cause of mortality associated with respiratory infections, we determined whether, in the absence of any known bacterial toxins, a deregulated host response resulting in sepsis syndrome is associated with lethality of respiratory infection with the virulent human type a strain schus4 of f. tularensis. the c57 ... | 2011 | 21440052 |
| infection of mice with francisella as an immunological model. | this unit describes the utility of various mouse models of infection for studying pathogenesis and adaptive immune responses to the facultative intracellular bacteria pathogen francisella tularensis. by judicious use of different combinations of mouse and bacterial strains, as well as different routes of infection, murine tularemia models may be used to explore a complete picture of f. tularensis infection and immunity. moreover, studies using francisella, particularly the live vaccine strain (l ... | 2011 | 21462168 |
| evasion of ifn-γ signaling by francisella novicida is dependent upon francisella outer membrane protein c. | francisella tularensis is a gram-negative facultative intracellular bacterium and the causative agent of the lethal disease tularemia. an outer membrane protein (ftt0918) of f. tularensis subsp. tularensis has been identified as a virulence factor. we generated a f. novicida (f. tularensis subsp. novicida) ftn_0444 (homolog of ftt0918) fopc mutant to study the virulence-associated mechanism(s) of ftt0918. | 2011 | 21483828 |
| tlr4-dependent activation of inflammatory cytokine response in macrophages by francisella elongation factor tu. | the bacterial determinants of pulmonary francisella induced inflammatory responses and their interaction with host components are not clearly defined. in this study, proteomic and immunoblot analyses showed presence of a cytoplasmic protein elongation factor tu (ef-tu) in the membrane fractions of virulent francisella novicida, lvs and schus4, but not in an attenuated f. novicida mutant. ef-tu was immunodominant in mice vaccinated and protected from virulent f. novicida. moreover, recombinant ef ... | 2011 | 21497800 |
| differential chitinase activity and production within francisella species, subspecies and subpopulations. | genotyping of francisella tularensis (a1a, a1b, a2 and type b) and francisella novicida has identified multiple differences between species, and among f. tularensis subspecies and subpopulations. variations in virulence, geographic distribution and ecology are also known to exist among this group of bacteria, despite the >95% nucleotide identity in their genomes. this study expands the description of phenotypic differences by evaluating the ability of f. tularensis and f. novicida to degrade chi ... | 2011 | 21531796 |