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rrp1, a cyclic-di-gmp-producing response regulator, is an important regulator of borrelia burgdorferi core cellular functions.two-component systems (tcs) are universal among bacteria and play critical roles in gene regulation. our understanding of the contributions of tcs in the biology of the borrelia is just now beginning to develop. borrelia burgdorferi, a causative agent of lyme disease, harbours a tcs comprised of open reading frames (orfs) bb0419 and bb0420. bb0419 encodes a response regulator designated rrp1, and bb0420 encodes a hybrid histidine kinase-response regulator designated hpk1. rrp1, which contains a ...200919210621
detailed analysis of sequence changes occurring during vlse antigenic variation in the mouse model of borrelia burgdorferi infection.lyme disease borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. the vls antigenic variation system, which expresses the surface-exposed lipoprotein vlse, plays a major role in b. burgdorferi immune evasion. gene conversion between vls silent cassettes and the vlse expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the vlse product. in this study, we examined vlse sequence variati ...200919214205
antigen-specific b-1a antibodies induced by francisella tularensis lps provide long-term protection against f. tularensis lvs challenge.francisella tularensis (ft), a gram-negative intracellular bacterium, is the etiologic agent of tularemia. infection of mice with <10 ft live vaccine strain (ft lvs) organisms i.p. causes a lethal infection that resembles human tularemia. here, we show that immunization with as little as 0.1 ng ft lvs lipopolysaccharide (ft-lps), but not ft lipid a, generates a rapid antibody response that protects wild-type (wt) mice against lethal ft lvs challenge. protection is not induced in ft-lps-immunized ...200919251656
local production of ifn-gamma by invariant nkt cells modulates acute lyme carditis.the lyme disease spirochete borrelia burgdorferi is the only known human pathogen that directly activates invariant nkt (inkt) cells. the number and activation kinetics of inkt cells vary greatly among different strains of mice. we now report the role of the inkt cell response in the pathogenesis of lyme disease using c57bl/6 mice, a strain with optimal inkt cell activation that is resistant to the development of spirochetal-induced inflammation. during experimental infection of b6 mice with b. ...200919265151
characterization of a novel relapsing fever spirochete in the midgut, coxal fluid, and salivary glands of the bat tick carios kelleyi.bat ticks, carios kelleyi, from iowa were examined for the presence of relapsing fever group borreliae. a novel spirochete was characterized by dna sequence analysis of polymerase chain reaction amplicons for the 16s rrna, flab, and glpq genes in either triturated tick pools or single ticks. all loci and the concatenated dna sequence of 3,289 bases identified the carios bacterium as a relapsing fever spirochete most closely related to, but distinct from, borrelia turicatae. spirochetes reactive ...200919281412
borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity.borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. here we identify for the first time a multifunctional surface lipoprotein of b. recurrentis, termed hcpa, and demonstrate that it binds human complement regulators, factor h, cfhr-1, and simultaneously, the host protease plasminogen. cell surface bound factor h was found to re ...200919308255
pilin gene variation in neisseria gonorrhoeae: reassessing the old paradigms.neisseria gonorrhoeae displays considerable potential for antigenic variation as shown in human experimental studies. various surface antigens can change either by antigenic variation using reca-dependent recombination schemes (e.g. pile antigenic variation) or, alternatively, through phase variation (on/off switching) in a reca-independent fashion (e.g. opa and lipooligosaccharide phase variation). pile antigenic variation has been well documented over the years. however, with the availability ...200919396954
identification of conserved antigens for early serodiagnosis of relapsing fever borrelia.borrelia hermsii is a blood-borne pathogen transmitted by the argasid tick ornithodoros hermsi. since spirochaete clearance in mice is associated with an igm-mediated response, an immunoproteomic analysis was used to identify proteins reactive with igm. we report that igm from both mice and human patients infected with b. hermsii not only reacted with the previously identified variable membrane proteins but also identified candidate antigens including heat-shock proteins, an adhesin protein, abc ...200919443544
roles for phagocytic cells and complement in controlling relapsing fever infection.relapsing fever spirochetes, such as borrelia hermsii, proliferate to high levels in their hosts' bloodstream until production of igm against borrelial surface proteins promotes bacterial clearance. the mechanisms by which b. hermsii survives in host blood, as well as the immune mediators that control this infection, remain largely unknown. it has been hypothesized that b. hermsii is naturally resistant to killing by the alternative pathway of complement activation as a result of its ability to ...200919458267
borrelia burgdorferi bb0426 encodes a 2'-deoxyribosyltransferase that plays a central role in purine salvage.borrelia burgdorferi is an obligate parasite with a limited genome that severely narrows its metabolic and biosynthetic capabilities. thus survival of this spirochaete in an arthropod vector and mammalian host requires that it can scavenge amino acids, fatty acids and nucleosides from a blood meal or various host tissues. additionally, the utilization of ribonucleotides for dna synthesis is further complicated by the lack of a ribonucleotide reductase for the conversion of nucleoside-5'-diphosph ...200919460093
chlamydia trachomatis-infected patients display variable antibody profiles against the nine-member polymorphic membrane protein family.genomic analysis of the chlamydiaceae has revealed a multigene family encoding large, putatively autotransported polymorphic membrane proteins (pmps) with nine members in the sexually transmitted pathogen chlamydia trachomatis. while various pathogenesis-related functions are emerging for the pmps, observed genotypic and phenotypic variation among several chlamydial pmps in various chlamydia species has led us to hypothesize that the pmp gene repertoire is the basis of a previously undetected me ...200919487469
generation of antigenic variants via gene conversion: evidence for recombination fitness selection at the locus level in anaplasma marginale.multiple bacterial and protozoal pathogens utilize gene conversion to generate antigenically variant surface proteins to evade immune clearance and establish persistent infection. both the donor alleles that encode the variants following recombination into an expression site and the donor loci themselves are under evolutionary selection: the alleles that encode variants that are sufficiently antigenically unique yet retain growth fitness and the loci that allow efficient recombination. we examin ...200919487473
understanding tropism and immunopathological mechanisms of relapsing fever spirochaetes.mice infected with relapsing fever (rf) spirochaetes survive recurrent waves of high-level bacteraemia with little, if any, clinical complications or tissue injury. in the absence of b-cells, peak bacteraemia does not resolve, resulting in multi-organ complications. during peak bacteraemia, large amounts of interleukin-10 (il-10) are produced in blood and tissues. in mice unable to clear peak bacteraemia, exogenous il-10 greatly reduced the clinical manifestations, serum levels of cxcl13, cerebr ...200919489924
genetic variation at the vlse locus of borrelia burgdorferi within ticks and mice over the course of a single transmission cycle.the lyme disease spirochete, borrelia burgdorferi, causes a persistent infection in the vertebrate host even though infected animals mount an active immune response against the spirochete. one strategy used by the spirochete to evade vertebrate host immunity is to vary the structure and expression of outer membrane antigens. the vlse locus represents the best-studied example of antigenic variation in b. burgdorferi. during vertebrate host infection, recombination between the active vlse locus an ...200312867452
igm in microbial infections: taken for granted?much has been learned about the structure, function, and production of igm, since the antibody's initial characterization. it is widely accepted that igm provides a first line of defense during microbial infections, prior to the generation of adaptive, high-affinity igg responses that are important for long-lived immunity and immunological memory. although igm responses are commonly used as a measure of exposure to infectious diseases, it is perhaps surprising that the role of and requirement fo ...200919539648
the evolved functions of cd1 during infection.cd1 proteins display lipid antigens to t cell receptors. studies using cd1d tetramers and cd1d-deficient mice provide important insight into the immunological functions of invariant nk t cells (inkt) during viral and bacterial infections. however, the mouse cd1 locus is atypical because it encodes only cd1d, whereas most mammalian species have retained many cd1 genes. viewed from the perspective that cd1 is a diverse gene family that activates several of classes of t cells, new insights into lip ...200919541469
in silico analysis of the cyclophilin repertoire of apicomplexan parasites.abstract:200919555495
identification of the determinant conferring permissive substrate usage in the telomere resolvase, rest.linear genome stability requires specialized telomere replication and protection mechanisms. a common solution to this problem in non-eukaryotes is the formation of hairpin telomeres by telomere resolvases (also known as protelomerases). these enzymes perform a two-step transesterification on replication intermediates to generate hairpin telomeres using an active site similar to that of tyrosine recombinases and type ib topoisomerases. unlike phage telomere resolvases, the telomere resolvase fro ...200919561077
complement factor h binding by different lyme disease and relapsing fever borrelia in animals and human.borreliae employ multiple immune evasive strategies such as binding to complement regulatory proteins [factor h (fh) and factor h like-1 (fhl1)], differential regulation of surface membrane proteins, antigenic variation, and binding of plasminogen/plasmin and matrix metalloproteinases. as a complement regulatory subunit, fh serves as a cofactor for the factor i-mediated cleavage of c3b. fh binding by borrelia has been correlated with pathogenesis as well as with host diversity. here we show the ...200919604355
comparative analysis of the properties and ligand binding characteristics of cspz, a factor h binding protein, derived from borrelia burgdorferi isolates of human origin.borrelia burgdorferi cspz (bbh06/bbcrasp-2) binds the complement regulatory protein factor h (fh) and additional unidentified serum proteins. the goals of this study were to assess the ligand binding capability of cspz orthologs derived from an extensive panel of human lyme disease isolates and to further define the molecular basis of the interaction between fh and cspz. while most b. burgdorferi cspz orthologs analyzed bound fh, specific, naturally occurring polymorphisms, most of which cluster ...200919620346
bacterial pathogens modulate an apoptosis differentiation program in human neutrophils.human polymorphonuclear leukocytes (pmns or neutrophils) are essential to the innate immune response against bacterial pathogens. recent evidence suggests that pmn apoptosis facilitates resolution of inflammation during bacterial infection. although progress has been made toward understanding apoptosis in neutrophils, very little is known about transcriptional regulation of this process during bacterial infection. to gain insight into the molecular processes that facilitate resolution of infecti ...200312960399
tick-borne relapsing fever caused by borrelia hermsii, montana.five persons contracted tick-borne relapsing fever after staying in a cabin in western montana. borrelia hermsii was isolated from the blood of two patients, and ornithodoros hermsi ticks were collected from the cabin, the first demonstration of this bacterium and tick in montana. relapsing fever should be considered when patients who reside or have vacationed in western montana exhibit a recurring febrile illness.200314519254
cd21/35 promotes protective immunity to streptococcus pneumoniae through a complement-independent but cd19-dependent pathway that regulates pd-1 expression.humoral immunity to t cell-independent type 2 ags (ti-2 ag) is critical for protection against encapsulated bacteria such as streptococcus pneumoniae. the cd21/35 receptor is thought to promote protective humoral immunity to encapsulated bacteria by enabling complement-decorated capsular polysaccharides to coligate the cd21/35-cd19 signaling complex with the b cell ag receptor (bcr), thereby enhancing ag-specific b cell activation. however, ab responses to s. pneumoniae type 3 capsular polysacch ...200919710450
sequence diversity of treponema pallidum subsp. pallidum tprk in human syphilis lesions and rabbit-propagated isolates.the tprk gene of treponema pallidum subsp. pallidum, the causative agent of venereal syphilis, belongs to a 12-member gene family and encodes a protein with a predicted cleavable signal sequence and predicted transmembrane domains. except for the nichols type strain, all rabbit-propagated isolates of t. pallidum examined thus far are comprised of mixed populations of organisms with heterogeneous tprk sequences. we show that tprk sequences in treponemes obtained directly from syphilis patients ar ...200314563860
platelet activation by a relapsing fever spirochaete results in enhanced bacterium-platelet interaction via integrin alphaiibbeta3 activation.borrelia hermsii, a spirochaete responsible for relapsing fever in humans, grows to high density in the bloodstream and causes thrombocytopenia. we show here that b. hermsii binds to human platelets. extended culture in bacteriological medium resulted in both diminished infectivity in vivo and diminished platelet binding in vitro. platelet binding was promoted by the platelet integrin alphaiibbeta3: the bacterium bound to purified integrin alphaiibbeta3, and bacterial binding to platelets was di ...200111136454
generation of b cell memory to the bacterial polysaccharide alpha-1,3 dextran.b1b b cells generate a novel form of memory and provide ab mediated-protection to persisting bacterial pathogens. to understand how b1b b cells establish memory to polysaccharide ags, we studied an oligoclonal b cell response to alpha-1,3 dextran (dex) expressed on enterobacter cloacae. b cells specific for dex enrich in the marginal zone (mz) and b1b b cell populations. after e. cloacae immunization, mz b cells were responsible for the generation of initial peak dex-specific ab titers, whereas, ...200919841173
structure-function investigation of vsp serotypes of the spirochete borrelia hermsii.relapsing fever (rf) spirochetes are notable for multiphasic antigenic variation of polymorphic outer membrane lipoproteins, a phenomenon responsible for immune evasion. an additional role in tissue localization is suggested by the finding that isogenic serotypes 1 (bt1) and 2 (bt2) of the rf spirochete borrelia turicatae, which differ only in the vsp they express, exhibit marked differences in clinical disease severity and tissue localization during infection.200919888463
evidence that two atp-dependent (lon) proteases in borrelia burgdorferi serve different functions.the canonical atp-dependent protease lon participates in an assortment of biological processes in bacteria, including the catalysis of damaged or senescent proteins and short-lived regulatory proteins. borrelia spirochetes are unusual in that they code for two putative atp-dependent lon homologs, lon-1 and lon-2. borrelia burgdorferi, the etiologic agent of lyme disease, is transmitted through the blood feeding of ixodes ticks. previous work in our laboratory reported that b. burgdorferi lon-1 i ...200919956677
identical strains of borrelia hermsii in mammal and bird. 200919961706
genetic control of the innate immune response to borrelia hermsii influences the course of relapsing fever in inbred strains of mice.host susceptibility to infection is controlled in large measure by the genetic makeup of the host. spirochetes of the genus borrelia include nearly 40 species of vector-borne spirochetes that are capable of infecting a wide range of mammalian hosts, causing lyme disease and relapsing fever. relapsing fever is associated with high-level bacteremia, as well as hematologic manifestations, such as thrombocytopenia (i.e., low platelet numbers) and anemia. to facilitate studies of genetic control of s ...201019995898
central role of the holliday junction helicase ruvab in vlse recombination and infectivity of borrelia burgdorferi.antigenic variation plays a vital role in the pathogenesis of many infectious bacteria and protozoa including borrelia burgdorferi, the causative agent of lyme disease. vlse, a 35 kda surface-exposed lipoprotein, undergoes antigenic variation during b. burgdorferi infection of mammalian hosts, and is believed to be a critical mechanism by which the spirochetes evade immune clearance. random, segmental recombination between the expressed vlse gene and adjacent vls silent cassettes generates a lar ...200919997622
size conversion of a linear plasmid in the relapsing fever agent borrelia duttonii.borreliae have genomes composed of both linear and circular replicons. we have characterized the organization of linear dna molecules from the borrelia duttonii strain ly. it contains a linear one megabase chromosome and 12 linear plasmids of 11 to 200 kb in size. a variant of the strain obtained after successive in vitro cultivation in bskii medium had a 69 kb molecule instead of the 44 kb linear plasmid. no detectable differences in the growth rates and cellular structures were found. southern ...200011220682
identification and molecular characterization of a cyclic-di-gmp effector protein, plza (bb0733): additional evidence for the existence of a functional cyclic-di-gmp regulatory network in the lyme disease spirochete, borrelia burgdorferi.the borrelia burgdorferi rrp1 protein is a diguanylate cyclase that controls a regulon consisting of approximately 10% of the total genome. because rrp1 lacks a dna-binding domain, its regulatory capability is most likely mediated through the production of bis-(3'-5')-cyclic dimeric gmp (c-di-gmp). c-di-gmp binds to and activates the regulatory activity of proteins that harbor a pilz domain. the occurrence of a pilz domain within a protein is not in and of itself sufficient to convey c-di-gmp bi ...201020030712
identification and molecular characterization of a cyclic-di-gmp effector protein, plza (bb0733): additional evidence for the existence of a functional cyclic-di-gmp regulatory network in the lyme disease spirochete, borrelia burgdorferi.the borrelia burgdorferi rrp1 protein is a diguanylate cyclase that controls a regulon consisting of approximately 10% of the total genome. because rrp1 lacks a dna-binding domain, its regulatory capability is most likely mediated through the production of bis-(3'-5')-cyclic dimeric gmp (c-di-gmp). c-di-gmp binds to and activates the regulatory activity of proteins that harbor a pilz domain. the occurrence of a pilz domain within a protein is not in and of itself sufficient to convey c-di-gmp bi ...201020030712
toll-like receptors--sentries in the b-cell response.toll-like receptors (tlr) play a central role in the initiation of the innate immune response to pathogens. upon recognition of molecular motifs specific for microbial molecules tlr mediate pro-inflammatory cytokine secretion and enhance antigen presentation; in b cells they further promote expansion, class switch recombination and immunoglobulin secretion. as a result of their adjuvant properties, tlr ligands have become an integral component of antimicrobial vaccines. in spite of this, little ...200920067531
a novel surface antigen of relapsing fever spirochetes can discriminate between relapsing fever and lyme borreliosis.in a previous immunoproteome analysis of borrelia hermsii, candidate antigens that bound igm antibodies from mice and patients infected with relapsing fever spirochetes were identified. one candidate that was identified is a hypothetical protein with a molecular mass of 57 kda that we have designated borrelia immunogenic protein a (bipa). this protein was further investigated as a potential diagnostic antigen for b. hermsii given that it is absent from the borrelia burgdorferi genome. the bipa l ...201020147497
leptospiral endostatin-like protein a is a bacterial cell surface receptor for human plasminogen.the spirochete leptospira interrogans is a highly invasive pathogen of worldwide public health importance. studies from our laboratories and another have demonstrated that l. interrogans can acquire host plasminogen on its surface. exogenous plasminogen activators can then convert bound plasminogen into the functionally active protease plasmin. in this study, we extend upon those observations and report that leptospiral endostatin-like protein a (lena) binds human plasminogen in a dose-dependent ...201020160016
genomic content of neisseria species.the physical properties of most bacterial genomes are largely unexplored. we have previously demonstrated that the strict human pathogen neisseria gonorrhoeae is polyploid, carrying an average of three chromosome copies per cell and only maintaining one pair of replication forks per chromosome (d. m. tobiason and h. s. seifert, plos biol. 4:1069-1078, 2006). we are following up this initial report to test several predictions of the polyploidy model of gonococcal chromosome organization. we demon ...201020172999
identification of residues within ligand-binding domain 1 (lbd1) of the borrelia burgdorferi ospc protein required for function in the mammalian environment.borrelia burgdorferi outer surface protein c (ospc) is required for the establishment of infection in mammals. however, its precise function remains controversial. the biologically active form of ospc appears to be a homodimer. alpha helix 1 and 1' of the apposing monomers form a solvent-accessible pocket at the dimeric interface that presents a putative ligand-binding domain (lbd1). here we employ site-directed and allelic-exchange mutagenesis to test the hypothesis that lbd1 is a determinant o ...201020199597
molecular characterization of the interaction of borrelia parkeri and borrelia turicatae with human complement regulators.in north america, tick-borne relapsing fever is caused by the species borrelia hermsii, b. parkeri, and b. turicatae, which are transmitted to humans through the bite of the respective infected tick vectors. here we describe the identification and functional characterization of a surface lipoprotein of b. parkeri, designated bpca, that binds the human complement regulators factor h and factor h-related protein 1 and, simultaneously, the host protease plasminogen. in contrast, the homologous b. t ...201020231403
induction of distinct neurologic disease manifestations during relapsing fever requires t lymphocytes.relapsing fever borreliosis is a multisystemic infection characterized primarily by bacteremia but can extend to the cns. the incidence of cns disease manifestations in humans depends on the infecting relapsing fever borrelia species. in the murine model of borrelia hermsii infection we found high incidence of distinct signs of cns disease that ranged from a flaccid tail to complete paralysis of hind limbs. infiltration of large number of t cells into the spinal cord of b. hermsii-infected mice ...201020382883
bacterial lipoproteins can disseminate from the periphery to inflame the brain.the current view is that bacteria need to enter the brain to cause inflammation. however, in mice infected with the spirochete borrelia turicatae, we observed widespread cerebral inflammation despite a paucity of spirochetes in the brain parenchyma at times of high bacteremia. here we studied the possibility that bacterial lipoproteins may be capable of disseminating from the periphery across the blood-brain barrier to inflame the brain. for this we injected normal and infected mice intraperiton ...201020431027
interaction of rickettsia felis with histone h2b facilitates the infection of a tick cell line.haematophagous arthropods are the primary vectors in the transmission of rickettsia, yet the molecular mechanisms mediating the rickettsial infection of arthropods remain elusive. this study utilized a biotinylated protein pull-down assay together with lc-ms/ms to identify interaction between ixodes scapularis histone h2b and rickettsia felis. co-immunoprecipitation of histone with rickettsial cell lysate demonstrated the association of h2b with r. felis proteins, including outer-membrane protei ...201020558510
t-cell-independent immune responses do not require cxc ligand 13-mediated b1 cell migration.the dynamic movement of b cells increases the probability of encountering specific antigen and facilitates cell-cell interactions required for mounting a rapid antibody response. b1a and b1b cells are enriched in the coelomic cavity, contribute to t-cell-independent (ti) antibody responses, and increase in number upon antigen exposure. b1 cell movement is largely governed by cxc ligand 13 (cxcl13), and mice deficient in this chemokine have a severe reduction in peritoneal b1 cells. in this study ...201020584971
invasion of mosquito salivary glands by malaria parasites: prerequisites and defense strategies.the interplay between vector and pathogen is essential for vector-borne disease transmission. dissecting the molecular basis of refractoriness of some vectors may pave the way to novel disease control mechanisms. a pathogen often needs to overcome several physical barriers, such as the peritrophic matrix, midgut epithelium and salivary glands. additionally, the arthropod vector elicites immune responses that can severely limit transmission success. one important step in the transmission of most ...201020621627
interleukin-10 mediated autoregulation of murine b-1 b-cells and its role in borrelia hermsii infection.b cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. however, recent studies indicate that various subsets of b cells can perform regulatory functions mainly through il-10 secretion. here we discovered that peritoneal b-1 (b-1p) cells produce high levels of il-10 upon stimulation with several toll-like receptor (tlr) ligands. high levels of il-10 suppressed b-1p cell proliferation and differentiation response to all tlr ligands stu ...201020625435
topo3alpha influences antigenic variation by monitoring expression-site-associated vsg switching in trypanosoma brucei.homologous recombination (hr) mediates one of the major mechanisms of trypanosome antigenic variation by placing a different variant surface glycoprotein (vsg) gene under the control of the active expression site (es). it is believed that the majority of vsg switching events occur by duplicative gene conversion, but only a few dna repair genes that are central to hr have been assigned a role in this process. gene conversion events that are associated with crossover are rarely seen in vsg switchi ...201020628569
toll-like receptor 2 deficiency results in impaired antibody responses and septic shock during borrelia hermsii infection.overwhelming bacteremia is a leading cause of death. to understand the mechanisms involved in protective antibody and pathological inflammatory responses during bacteremia, we have been studying the murine model of borrelia hermsii infection. toll-like receptor (tlr) signaling plays an important role in generating the rapid anti-b. hermsii antibody responses required for the resolution of bacteremia. using nf-κb reporter assays, we found that b. hermsii activates tlr2 and tlr9. however, tlr2(-/- ...201020696824
an extreme thermophile, thermus thermophilus, is a polyploid bacterium.an extremely thermophilic bacterium, thermus thermophilus hb8, is one of the model organisms for systems biology. its genome consists of a chromosome (1.85 mb), a megaplasmid (0.26 mb) designated ptt27, and a plasmid (9.3 kb) designated ptt8, and the complete sequence is available. we show here that t. thermophilus is a polyploid organism, harboring multiple genomic copies in a cell. in the case of the hb8 strain, the copy number of the chromosome was estimated to be four or five, and the copy n ...201020729360
human granulocytic anaplasmosis: first reported case in canada.human granulocytic anaplasmosis (hga) is a tick-borne rickettsial infection of peripheral blood neutrophils caused by anaplasma phagocytophilum. while this infection is increasingly recognized as endemic throughout much of the united states, no canadian cases have been previously described, despite the agent being identified in canadian ticks. herein we present a case of hga acquired in an urban alberta centre. canadian physicians must be aware of the possibility of tick-borne rickettsial diseas ...200920808448
rapid typing of borrelia burgdorferi sensu lato species in specimens from patients with different manifestations of lyme borreliosis.to further investigate the pathogenic potential of different borrelia burgdorferi genospecies, specimens from 27 patients with different manifestations of lyme borreliosis were analyzed by pcr and reverse line blotting (rlb). in samples from lyme arthritis patients, b. burgdorferi sensu stricto was predominantly identified, while in patients with neuroborreliosis or acrodermatitis, borrelia garinii and borrelia afzelii, respectively, were exclusively detected. the results demonstrate that pcr-rl ...200111230440
evolution and distribution of the ospc gene, a transferable serotype determinant of borrelia burgdorferi.borrelia burgdorferi, an emerging bacterial pathogen, is maintained in nature by transmission from one vertebrate host to another by ticks. one of the few antigens against which mammals develop protective immunity is the highly polymorphic ospc protein, encoded by the ospc gene on the cp26 plasmid. intragenic recombination among ospc genes is known, but the extent to which recombination extended beyond the ospc locus itself is undefined. we accessed and supplemented collections of dna sequences ...201020877579
the innate immune adaptor molecule myd88 restricts west nile virus replication and spread in neurons of the central nervous system.type i interferons (ifn-α/β) control viral infection by triggering the expression of genes that restrict transcription, translation, replication, and assembly. many viruses induce ifn responses after recognition by cytoplasmic or endosomal rna sensors (rig-i-like rna helicases [rlr] and toll-like receptors [tlr]), which signal through the cognate adaptor signaling molecules ips-1, trif, and myd88. recent studies have demonstrated that ips-1-dependent induction of ifn-α/β downstream of rlr recogn ...201020881045
genome copy numbers and gene conversion in methanogenic archaea.previous studies revealed that one species of methanogenic archaea, methanocaldococcus jannaschii, is polyploid, while a second species, methanothermobacter thermoautotrophicus, is diploid. to further investigate the distribution of ploidy in methanogenic archaea, species of two additional genera-methanosarcina acetivorans and methanococcus maripaludis-were investigated. m. acetivorans was found to be polyploid during fast growth (t(d) = 6 h; 17 genome copies) and oligoploid during slow growth ( ...201021097629
genome copy numbers and gene conversion in methanogenic archaea.previous studies revealed that one species of methanogenic archaea, methanocaldococcus jannaschii, is polyploid, while a second species, methanothermobacter thermoautotrophicus, is diploid. to further investigate the distribution of ploidy in methanogenic archaea, species of two additional genera-methanosarcina acetivorans and methanococcus maripaludis-were investigated. m. acetivorans was found to be polyploid during fast growth (t(d) = 6 h; 17 genome copies) and oligoploid during slow growth ( ...201021097629
borrelia burgdorferi and treponema pallidum: a comparison of functional genomics, environmental adaptations, and pathogenic mechanisms. 200111254661
igm production by bone marrow plasmablasts contributes to long-term protection against intracellular bacterial infection.igm responses are well known to occur early postinfection and tend to be short-lived, which has suggested that this ig does not significantly contribute to long-term immunity. in this study, we demonstrate that chronic infection with the intracellular bacterium ehrlichia muris elicits a protective, long-term igm response. moreover, we identified a population of cd138(high)igm(high) b cells responsible for ag-specific igm production in the bone marrow. the igm-secreting cells, which exhibited cha ...201021148037
igm production by bone marrow plasmablasts contributes to long-term protection against intracellular bacterial infection.igm responses are well known to occur early postinfection and tend to be short-lived, which has suggested that this ig does not significantly contribute to long-term immunity. in this study, we demonstrate that chronic infection with the intracellular bacterium ehrlichia muris elicits a protective, long-term igm response. moreover, we identified a population of cd138(high)igm(high) b cells responsible for ag-specific igm production in the bone marrow. the igm-secreting cells, which exhibited cha ...201021148037
c-terminal invariable domain of vlse is immunodominant but its antigenicity is scarcely conserved among strains of lyme disease spirochetes.vlse, the variable surface antigen of borrelia burgdorferi, contains two invariable domains located at the amino and carboxyl terminal ends, respectively, and a central variable domain. in this study, both immunogenicity and antigenic conservation of the c-terminal invariable domain were assessed. mouse antiserum to a 51-mer synthetic peptide (ct) which reproduced the entire sequence of the c-terminal invariable domain of vlse from b. burgdorferi strain b31 was reacted on immunoblots with whole- ...200111292744
bloodmeal size and spirochete acquisition of ornithodoros hermsi (acari: argasidae) during feeding.ornithodoros hermsi wheeler (acari: argasidae) is the vector of borrelia hermsii, the primary cause of tick-borne relapsing fever in north america. this tick is one of the smallest ornithodoros species involved with the biological transmission of spirochetes; yet, the amount of blood ingested while feeding is unknown. therefore, we determined the amount of blood o. hermsi ingested during a bloodmeal to establish its potential for spirochete acquisition while feeding on an infected host. ticks at ...201021175068
intrachromosomal recombination within the vsp locus of mycoplasma bovis generates a chimeric variable surface lipoprotein antigen.a family of 13 related but divergent vsp genes was recently found in the chromosome of the bovine pathogen mycoplasma bovis. the vsp genomic locus was shown to undergo high-frequency rearrangements and to mediate phenotypic switching of variable lipoprotein antigens (vsps) on the mycoplasma cell surface. here we report that the vsp gene repertoire is subject to changes. genetic analysis of m. bovis clonal isolates displaying distinct vsp phenotypes showed that an intergenic recombination event b ...200111349034
analysis of phase-specific gene expression at the single-cell level in the white-opaque switching system of candida albicans.the opportunistic fungal pathogen candida albicans can switch spontaneously and reversibly between different cell forms, a capacity that may enhance adaptation to different host niches and evasion of host defense mechanisms. phenotypic switching has been studied intensively for the white-opaque switching system of strain wo-1. to facilitate the molecular analysis of phenotypic switching, we have constructed homozygous ura3 mutants from strain wo-1 by targeted gene deletion. the two ura3 alleles ...200111371541
activation of myd88 signaling upon staphylococcal enterotoxin binding to mhc class ii molecules.ligands binding to toll-like receptor (tlr), interleukin 1 receptor (il-1r), or ifn-?r1 are known to trigger myd88-mediated signaling, which activates pro-inflammatory cytokine responses. recently we reported that staphylococcal enterotoxins (sea or seb), which bind to mhc class ii molecules on apcs and cross link t cell receptors, activate myd88- mediated pro-inflammatory cytokine responses. we also reported that myd88(-/-) mice were resistant to se- induced toxic shock and had reduced levels o ...201121283748
quantification of ploidy in proteobacteria revealed the existence of monoploid, (mero-)oligoploid and polyploid species.bacteria are generally assumed to be monoploid (haploid). this assumption is mainly based on generalization of the results obtained with the most intensely studied model bacterium, escherichia coli (a gamma-proteobacterium), which is monoploid during very slow growth. however, several species of proteobacteria are oligo- or polyploid, respectively. to get a better overview of the distribution of ploidy levels, genome copy numbers were quantified in four species of three different groups of prote ...201121305010
antigenic variation in plasmodium falciparum malaria involves a highly structured switching pattern.many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. in the human malaria parasite plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populati ...201121408201
cross-species hybridization of a borrelia burgdorferi dna array reveals infection- and culture-associated genes of the unsequenced genome of the relapsing fever agent borrelia hermsii.the known genome sequence of borrelia burgdorferi, an agent of lyme borreliosis, was used to study the genetic content and gene expression in b. hermsii, another spirochete pathogen and a cause of relapsing fever. cross-species hybridization of a dna array representing 1628 open reading frames (orf) of b. burgdorferi with genomic dna of b. hermsii indicated that the latter organism has at least 81% of the chromosomal genes and 43% of the plasmid genes of b. burgdorferi. we then carried out quant ...200414731275
genetic transformation of the relapsing fever spirochete borrelia hermsii: stable integration and expression of green fluorescent protein from linear plasmid 200 (lp200).tick-borne relapsing fever (tbrf) is a spirochetal disease caused by at least 15 different borrelia species. it is a serious human health concern in endemic regions of the world. transmission to humans occurs through the bites of infected ornithordoros ticks. in north america, the primary borrelia species associated with human disease are b. hermsii and b. turicatae. direct demonstration of the role of putative tbrf spirochete virulence factors in the disease process has been hindered by the lac ...201121551306
a hypomorphic igh-chain allele affects development of b-cell subsets and favours receptor editing.the quality and quantity of bcr signals impact on cell fate decisions of b lymphocytes. here, we describe novel gene-targeted mice, which in the context of normal vdj recombination show hypomorphic expression of immunoglobulin μ heavy chain (μhc) mrna levels and hence lower pre-bcr and bcr levels. hypomorphic expression of μhc leads to augmented selection processes at all stages of b-cell development, noticeably at the expansion of pre-b cells, the positive selection of immature b lymphocytes in ...201121623346
alveolar septal deposition of immunoglobulin and complement parallels pulmonary hemorrhage in a guinea pig model of severe pulmonary leptospirosis.human patients suffering from leptospirosis present with a diverse array of clinical manifestations, including the more severe and often fatal pulmonary form of the disease. the etiology of pulmonary hemorrhage is unclear. isolates of leptospira acquired from patients suffering from pulmonary hemorrhage were used to develop a guinea pig model of pulmonary hemorrhage. gross findings post-infection confirmed extensive hemorrhage in the lungs and on peritoneal surfaces as the likely cause of death. ...200414982864
focusing homologous recombination: pilin antigenic variation in the pathogenic neisseria.some pathogenic microbes utilize homologous recombination to generate antigenic variability in targets of immune surveillance. these specialized systems rely on the cellular recombination machinery to catalyse dedicated, high-frequency reactions that provide extensive diversity in the genes encoding surface antigens. a description of the specific mechanisms that allow unusually high rates of recombination without deleterious effects on the genome in the well-characterized pilin antigenic variati ...201121812841
[genetic features of borrelia miyamotoi transmitted by ixodes persulcatus].the definition and molecular typing of borrelia miyamotoi transmitted by the ixodes persuccatus ticks was based on the partial sequencing of the 16s rrna, p66, and glpq genes. all the b. miyamotoi analyzed sequences of the 16s rrna, glpq, and p66 gene fragments from i. persulcatus were identical and had 99.9-100% similarity to corresponding genes of the b. miyamotoi strain fr64b isolated in japan. the analyzed amino acid sequences revealed that the 66 protein b. miyamotoi in the site correspondi ...201121786631
nidicolous ticks of small mammals in anaplasma phagocytophilum-enzootic sites in northern california.ixodes spp. tick-borne zoonotic diseases are present across the holarctic in humans, domestic animals, and wildlife. small mammals are reservoirs for the rickettsial pathogen anaplasma phagocytophilum and tick vectors may include catholic-feeding bridge vectors as well as host-specialist or nidicolous ticks. far western north american communities in which a. phagocytophilum is maintained are complex ecologically, with multiple reservoir host and tick species, multiple strains of the bacterial pa ...201121686062
human immune system mice: current potential and limitations for translational research on human antibody responses.it has recently become possible to generate chimeric mice durably engrafted with many components of the human immune system (his mice). we have characterized the maturation and function of the b cell compartment of his mice. the antibody response of his mice to t cell-dependent b cell antigens is limited, and contributing factors may be the general immaturity of the b cell compartment, infrequent helper t cells selected on human mhc class ii antigens, and incomplete reconstitution of secondary l ...201122038527
Acquisition and subsequent transmission of Borrelia hermsii by the soft tick Ornithodoros hermsi.Tick-borne relapsing fever is caused by spirochetes within the genus Borrelia. The hallmark of this disease is recurrent febrile episodes and high spirochete densities in mammalian blood resulting from immune evasion. Between episodes of spirochetemia when bacterial densities are low, it is unknown whether ticks can acquire the spirochetes, become colonized by the bacteria, and subsequently transmit the bacteria once they feed again. We addressed these questions by feeding ticks, Omnithodoros he ...201121845950
b1b lymphocytes confer t cell-independent long-lasting immunity.many microbial pathogens employ antigenic variation as a strategy to evade the immune system, posing a challenge in vaccine development. to understand the requirements for immunity against such pathogens, we studied borrelia hermsii, a relapsing fever bacterium. we found that mice deficient in t, follicular b, marginal zone b, or b1a lymphocytes resolved b. hersmii bacteremia and became resistant to reinfection. the resolution of bacteremia coincided with an expansion and persistence of b1b lymp ...200415357949
B1b lymphocyte-derived antibodies control Borrelia hermsii independent of Fca/µ receptor and in the absence of host cell contact.The critical role of IgM in controlling pathogen burden has been demonstrated in a variety of infection models. In the murine model of Borrelia hermsii infection, IgM is necessary and sufficient for the rapid clearance of bacteremia. Convalescent, but not naïve, B1b cells generate a specific IgM response against B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we show that neither Fca/µR, a high-affinity receptor for IgM, nor IgM-dependent complement activation is requi ...201122139824
within-host dynamics of antigenic variation.genomes of some parasites contain dozens of alternative and highly diverged surface antigens, of which only a single one is expressed in any cell. individual cells occasionally change expression of their surface antigen, allowing them to escape immune surveillance. these switches appear to occur in a partly random way, creating a diverse set of antigenic variants. in spite of this diversity, the parasitemia develops as a series of outbreaks, in which each outbreak is dominated by relatively few ...200616461018
cotransmission of divergent relapsing fever spirochetes by artificially infected ornithodoros hermsi.the soft tick ornithodoros hermsi, which ranges in specific arboreal zones of western north america, acts as a vector for the relapsing fever spirochete borrelia hermsii. two genomic groups (genomic group i [ggi] and ggii) of b. hermsii are differentiated by multilocus sequence typing yet are codistributed in much of the vector's range. to test whether the tick vector can be infected via immersion, noninfected, colony-derived o. hermsi larvae were exposed to reduced-humidity conditions before im ...201121965393
antigenic variation with a twist--the borrelia story.a common mechanism of immune evasion in pathogenic bacteria and protozoa is antigenic variation, in which genetic or epigenetic changes result in rapid, sequential shifts in a surface-exposed antigen. in this issue of molecular microbiology, dai et al. provide the most complete description to date of the vlp/vsp antigenic variation system of the relapsing fever spirochaete, borrelia hermsii. this elaborate, plasmid-encoded system involves an expression site that can acquire either variable large ...200616796669
dual binding specificity of a borrelia hermsii-associated complement regulator-acquiring surface protein for factor h and plasminogen discloses a putative virulence factor of relapsing fever spirochetes.tick-borne relapsing fever in north america is primarily caused by the spirochete borrelia hermsii. the pathogen employs multiple strategies, including the acquisition of complement regulators and antigenic variation, to escape innate and humoral immunity. in this study we identified in b. hermsii a novel member of the complement regulator-acquiring surface protein (crasp) family, designated bhcrasp-1, that binds the complement regulators factor h (fh) and fh-related protein 1 (fhr-1) but not fh ...200717513779
programmed cell death 1 suppresses b-1b cell expansion and long-lived igg production in response to t cell-independent type 2 antigens.b-1b cells play a key role in producing abs against t cell-independent type 2 ags. however, the factors regulating ab production by this unique b cell subset are not well understood. in this study, a detailed analysis of the b cell response to 2,4,6-trinitrophenol (tnp)-ficoll was performed using normal mice. tnp-ficoll delivered i.p. or i.v. induced rapid ag-specific b-1b cell activation, expansion, isotype switching, and plasmablast/plasma cell differentiation. ag-specific b-1b cell numbers pe ...201122003198
Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever.Rodents are natural reservoirs for a variety of species of Borrelia that cause relapsing fever (RF) in humans. The murine model of this disease recapitulates many of the clinical manifestations of the human disease and has revealed that T cell-independent antibody responses are required to resolve the bacteremic episodes. However, it is not clear whether such protective humoral responses are mounted in humans. We examined Borrelia hermsii infection in human hematopoietic stem cell-engrafted nono ...201122143787
phenotypic and functional heterogeneity of human memory b cells.memory b cells are more heterogeneous than previously thought. given that b cells play powerful antibody-independent effector functions, it seems reasonable to assume division of labor between distinct memory b cells subpopulations in both protective and pathogenic immune responses. here we review the information emerging regarding the heterogeneity of human memory b cells. a better understanding of this topic should greatly improve our ability to target specific b cell subsets either in vaccine ...200818258454
microbial antigenic variation mediated by homologous dna recombination.pathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. one of the most widely used strategies of immune evasion is antigenic variation, in which immunogenic molecules expressed on the surface of a microorganism are continuously modified. as a consequence, the host is forced to constantly adapt its humoral immune response against this pathogen. an antigenic change thus provides the microorganism with an opport ...201122212019
marginal zone b-cells, a gatekeeper of innate immunity.to maintain the integrity of an organism constantly challenged by pathogens, the immune system is endowed with a variety of cell types. b lymphocytes were initially thought to only play a role in the adaptive branch of immunity. however, a number of converging observations revealed that two b-cell subsets, marginal zone (mz) and b1 cells, exhibit unique developmental and functional characteristics, and can contribute to innate immune responses. in addition to their capacity to mount a local anti ...201122566852
regulatory b cell (b10 cell) expansion during listeria infection governs innate and cellular immune responses in mice.pathogens use numerous methods to subvert host immune responses, including the modulation of host il-10 production by diverse cell types. however, the b cell sources of il-10 and their overall influence on innate and cellular immune responses have not been well characterized during infections. using listeria as a model pathogen, infection drove the acute expansion of a small subset of regulatory b cells (b10 cells) that potently suppress inflammation and autoimmunity through the production of il ...201223275601
regulatory b cell (b10 cell) expansion during listeria infection governs innate and cellular immune responses in mice.pathogens use numerous methods to subvert host immune responses, including the modulation of host il-10 production by diverse cell types. however, the b cell sources of il-10 and their overall influence on innate and cellular immune responses have not been well characterized during infections. using listeria as a model pathogen, infection drove the acute expansion of a small subset of regulatory b cells (b10 cells) that potently suppress inflammation and autoimmunity through the production of il ...201223275601
annotation of protein domains reveals remarkable conservation in the functional make up of proteomes across superkingdoms.the functional repertoire of a cell is largely embodied in its proteome, the collection of proteins encoded in the genome of an organism. the molecular functions of proteins are the direct consequence of their structure and structure can be inferred from sequence using hidden markov models of structural recognition. here we analyze the functional annotation of protein domain structures in almost a thousand sequenced genomes, exploring the functional and structural diversity of proteomes. we find ...201124710297
novel diagnosis of lyme disease: potential for cam intervention.lyme disease (ld) is the most common tick-borne disease in the northern hemisphere, producing a wide range of disabling effects on multiple human targets, including the skin, the nervous system, the joints and the heart. insufficient clinical diagnostic methods, the necessity for prompt antibiotic treatment along with the pervasive nature of infection impel the development and establishment of new clinical diagnostic tools with increased accuracy, sensitivity and specificity. the goal of this ar ...200918955246
novel diagnosis of lyme disease: potential for cam intervention.lyme disease (ld) is the most common tick-borne disease in the northern hemisphere, producing a wide range of disabling effects on multiple human targets, including the skin, the nervous system, the joints and the heart. insufficient clinical diagnostic methods, the necessity for prompt antibiotic treatment along with the pervasive nature of infection impel the development and establishment of new clinical diagnostic tools with increased accuracy, sensitivity and specificity. the goal of this ar ...200918955246
classification and evolutionary history of the single-strand annealing proteins, rect, redbeta, erf and rad52.the dna single-strand annealing proteins (ssaps), such as rect, redbeta, erf and rad52, function in reca-dependent and reca-independent dna recombination pathways. recently, they have been shown to form similar helical quaternary superstructures. however, despite the functional similarities between these diverse ssaps, their actual evolutionary affinities are poorly understood.200211914131
phase and antigenic variation in bacteria.phase and antigenic variation result in a heterogenic phenotype of a clonal bacterial population, in which individual cells either express the phase-variable protein(s) or not, or express one of multiple antigenic forms of the protein, respectively. this form of regulation has been identified mainly, but by no means exclusively, for a wide variety of surface structures in animal pathogens and is implicated as a virulence strategy. this review provides an overview of the many bacterial proteins a ...200415258095
glycolipids as immunostimulating agents.the processing and presentation of lipid antigens by antigen presenting cells (apc) is important for defense against infection, tumor immunosurveillance, and autoimmunity. cd1, a family of cell surface glycoproteins, is responsible for the binding and presentation of lipid antigens to receptors expressed on the surface of t lymphocytes. among the several (glyco)lipids identified to cause t-cell stimulation in complex with cd1, alpha-galactosyl ceramide (alpha-galcer) is one of the most well stud ...200718006319
glycolipids as immunostimulating agents.the processing and presentation of lipid antigens by antigen presenting cells (apc) is important for defense against infection, tumor immunosurveillance, and autoimmunity. cd1, a family of cell surface glycoproteins, is responsible for the binding and presentation of lipid antigens to receptors expressed on the surface of t lymphocytes. among the several (glyco)lipids identified to cause t-cell stimulation in complex with cd1, alpha-galactosyl ceramide (alpha-galcer) is one of the most well stud ...200718006319
functional representation of enzymes by specific peptides.predicting the function of a protein from its sequence is a long-standing goal of bioinformatic research. while sequence similarity is the most popular tool used for this purpose, sequence motifs may also subserve this goal. here we develop a motif-based method consisting of applying an unsupervised motif extraction algorithm (mex) to all enzyme sequences, and filtering the results by the four-level classification hierarchy of the enzyme commission (ec). the resulting motifs serve as specific pe ...200717722976
comparative cryo-electron tomography of pathogenic lyme disease spirochetes.spirochetes of the borrelia burgdorferi sensu lato group, the causative agents of lyme borreliosis, exhibit a complex biology evolved in its zoonotic cycle. cryo-electron tomography was used to investigate structural features of three species, b. burgdorferi, b. garinii and b. afzelii, known to cause different clinical manifestations in humans. all three organisms revealed an overall similar architecture and showed different numbers of periplasmic flagellar filaments, polar periplasmic void regi ...200919210619
complex population structure of lyme borreliosis group spirochete borrelia garinii in subarctic eurasia.borrelia garinii, a causative agent of lyme borreliosis in europe and asia, is naturally maintained in marine and terrestrial enzootic cycles, which primarily involve birds, including seabirds and migratory passerines. these bird groups associate with, correspondingly, ixodes uriae and ixodes ricinus ticks, of which the latter species may bite and transmit the infection to humans. studies of the overlap between these two natural cycles of b. garinii have been limited, in part due to the absence ...200919513109
tick-borne relapsing fever and borrelia hermsii, los angeles county, california, usa.the primary cause of tick-borne relapsing fever in western north america is borrelia hermsii, a rodent-associated spirochete transmitted by the fast-feeding soft tick ornithodoros hermsi. we describe a patient who had an illness consistent with relapsing fever after exposure in the mountains near los angeles, california, usa. the patient's convalescent-phase serum was seropositive for b. hermsii but negative for several other vector-borne bacterial pathogens. investigations at the exposure site ...200919624916
a pattern analysis of gene conversion literature.gene conversion is an important biological process that involves the transfer of genetic (sequence) information from one gene to another. this can have a variety of effects on an organism, both short-term and long-term and both positive and detrimental. in an effort to better understand this process, we searched through over 3,000 abstracts that contain research on gene conversions, tagging the important data and performing an analysis on what we extract. through this we established trends that ...201020148076
a pattern analysis of gene conversion literature.gene conversion is an important biological process that involves the transfer of genetic (sequence) information from one gene to another. this can have a variety of effects on an organism, both short-term and long-term and both positive and detrimental. in an effort to better understand this process, we searched through over 3,000 abstracts that contain research on gene conversions, tagging the important data and performing an analysis on what we extract. through this we established trends that ...201020148076
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