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Sample records for fever spirochete borrelia

  1. First isolation of the relapsing fever spirochete, Borrelia hermsii, from a domestic dog

    PubMed Central

    Kelly, Ashley L.; Raffel, Sandra J.; Fischer, Robert J.; Bellinghausen, Michael; Stevenson, Connie; Schwan, Tom G.

    2014-01-01

    In North America, tick-borne relapsing fever of humans is most frequently caused by infection with the spirochete Borrelia hermsii. Prior to our investigation, this spirochete was not known to infect dogs although another species, Borrelia turicatae, has been isolated from domestic canids in Florida and Texas. A clinically ill dog in Washington, USA, was spirochetemic upon examination. Spirochetes were isolated from the dog’s serum and examined by PCR and multi-locus sequence typing. DNA sequences for 7 loci all typed the spirochete as B. hermsii and a member of genomic group II of this species. Therefore, companion dogs that reside in rustic cabins in higher elevation forests are at risk of infection with B. hermsii. PMID:24252262

  2. Susceptibility of Various Species of Rodents to the Relapsing Fever Spirochete, Borrelia hermsii.

    PubMed

    Burgdorfer, W; Mavros, A J

    1970-09-01

    In a study to determine susceptibility to Borrelia hermsii of various rodents commonly found in or near places where human cases of relapsing fever occurred, chipmunks (Eutamias amoenus), pine squirrels (Tamiasciurus hudsonicus richardsoni), flying squirrels (Glaucomys sabrinus), Columbian ground squirrels (Spermophilus columbianus columbianus), golden-mantled ground squirrels (S. lateralis tescorum), wood rats (Neotoma cinerea cinerea), white-footed deer mice (Peromyscus maniculatus), and meadow voles (Microtus pennsylvanicus) were exposed to spirochetes either by bites of infected Ornithodoros hermsi or by injection of infectious tick suspensions. Daily microscopic examination of blood samples revealed that pine squirrels, chipmunks, and meadow voles responded with spirochetemias of various degrees and length. Pine squirrels were most susceptible and experienced long-lasting and severe spirochetemias accompanied by typical signs of illness. Flying squirrels, Columbian ground squirrels, golden-mantled ground squirrels, wood rats, and white-footed deer mice did not develop demonstrable spirochetal infection. PMID:16557828

  3. Susceptibility of Various Species of Rodents to the Relapsing Fever Spirochete, Borrelia hermsii

    PubMed Central

    Burgdorfer, Willy; Mavros, Anthony J.

    1970-01-01

    In a study to determine susceptibility to Borrelia hermsii of various rodents commonly found in or near places where human cases of relapsing fever occurred, chipmunks (Eutamias amoenus), pine squirrels (Tamiasciurus hudsonicus richardsoni), flying squirrels (Glaucomys sabrinus), Columbian ground squirrels (Spermophilus columbianus columbianus), golden-mantled ground squirrels (S. lateralis tescorum), wood rats (Neotoma cinerea cinerea), white-footed deer mice (Peromyscus maniculatus), and meadow voles (Microtus pennsylvanicus) were exposed to spirochetes either by bites of infected Ornithodoros hermsi or by injection of infectious tick suspensions. Daily microscopic examination of blood samples revealed that pine squirrels, chipmunks, and meadow voles responded with spirochetemias of various degrees and length. Pine squirrels were most susceptible and experienced long-lasting and severe spirochetemias accompanied by typical signs of illness. Flying squirrels, Columbian ground squirrels, golden-mantled ground squirrels, wood rats, and white-footed deer mice did not develop demonstrable spirochetal infection. Images PMID:16557828

  4. Detection of a Borrelia miyamotoi sensu lato relapsing-fever group spirochete from Ixodes pacificus in California.

    PubMed

    Mun, Jeomhee; Eisen, Rebecca J; Eisen, Lars; Lane, Robert S

    2006-01-01

    We investigated whether host-seeking nymphs and adults of the western blacklegged tick, Ixodes pacificus Cooley & Kohls, the primary vector of Lyme disease spirochetes in far-western North America, are infected naturally with relapsing-fever group spirochetes in Mendocino County, California. Relapsing-fever group borreliae were detected in four (1.7%) of 234 nymphal and two (0.7%) of 282 adult host-seeking I. pacificus ticks by polymerase chain reaction and sequence analysis of the 16S rRNA and flagellin genes, respectively, exhibiting 99 and 98.5% sequence homology to Borrelia miyamotoi Fukunaga. Phylogenetic analysis based on these two genes revealed that the borreliae detected in these ticks belong to the relapsing-fever group and that these are closely related to, if not identical with, B. miyamotoi. PMID:16506458

  5. Tick Surveillance for Relapsing Fever Spirochete Borrelia miyamotoi in Hokkaido, Japan

    PubMed Central

    Konnai, Satoru; Ohashi, Kazuhiko; Nakao, Minoru; Ito, Takuya; Andoh, Masako; Maeda, Ken; Watarai, Masahisa; Sato, Kozue; Kawabata, Hiroki

    2014-01-01

    During 2012–2013, a total of 4325 host-seeking adult ticks belonging to the genus Ixodes were collected from various localities of Hokkaido, the northernmost island of Japan. Tick lysates were subjected to real-time PCR assay to detect borrelial infection. The assay was designed for specific detection of the Relapsing fever spirochete Borrelia miyamotoi and for unspecific detection of Lyme disease-related spirochetes. Overall prevalence of B. miyamotoi was 2% (71/3532) in Ixodes persulcatus, 4.3% (5/117) in Ixodes pavlovskyi and 0.1% (1/676) in Ixodes ovatus. The prevalence in I. persulcatus and I. pavlovskyi ticks were significantly higher than in I. ovatus. Co-infections with Lyme disease-related spirochetes were found in all of the tick species. During this investigation, we obtained 6 isolates of B. miyamotoi from I. persulcatus and I. pavlovskyi by culture in BSK-M medium. Phylogenetic trees of B. miyamotoi inferred from each of 3 housekeeping genes (glpQ, 16S rDNA, and flaB) demonstrated that the Hokkaido isolates were clustered with Russian B. miyamotoi, but were distinguishable from North American and European B. miyamotoi. A multilocus sequence analysis using 8 genes (clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA) suggested that all Japanese B. miyamotoi isolates, including past isolates, were genetically clonal, although these were isolated from different tick and vertebrate sources. From these results, B. miyamotoi-infected ticks are widely distributed throughout Hokkaido. Female I. persulcatus are responsible for most human tick-bites, thereby I. persulcatus is likely the most important vector of indigenous relapsing fever from tick bites in Hokkaido. PMID:25111141

  6. Detection of relapsing fever spirochetes (Borrelia hermsii and Borrelia coriaceae) in free-ranging mule deer (Odocoileus hemionus) from Nevada, United States.

    PubMed

    Nieto, Nathan C; Teglas, Mike B; Stewart, Kelley M; Wasley, Tony; Wolff, Peregrine L

    2012-02-01

    Surveillance of mule deer (Odocoileus hemionus, Rafinesque, 1917) populations for tick-borne diseases has helped define the distribution of these pathogens and their subsequent risk of transmission to humans and domestic animals. We surveyed three mule deer herds across the state of Nevada for infection with relapsing fever Borrelia spp. spirochetes. Bacterial prevalence varied by the county where deer were sampled but Borrelia spirochetes were detected in 7.7% of all deer sampled. Infected deer were identified in every location from which mule deer samples were obtained. Sequencing of the Borrelia intergenic spacer gene (IGS) revealed that one individual was infected with Borrelia coriaceae and all others were infected with Borrelia hermsii. The vector of B. hermsii, Ornithodoros hermsi (Acari: Argasidae, Wheeler, Herms, and Meyer, 1935), feeds primarily on wild rodents and has not been identified infesting deer. Additionally, Ornithodoros coriaceus (Acari: Argasidae, Koch, 1844), which readily feeds on deer and is frequently infected with B. coriaceae, has not been shown to be a competent vector for B. hermsii. Our data represent the first sylvatic evidence of B. hermsii infection in mule deer. Additionally, our data provide evidence that infection with relapsing fever spirochetes in Nevada is wide ranging in the state's deer populations.

  7. Variable Tick Protein in Two Genomic Groups of the Relapsing Fever Spirochete Borrelia hermsii in Western North America

    PubMed Central

    Porcella, Stephen F.; Raffel, Sandra J.; Anderson, Donald E.; Gilk, Stacey D.; Bono, James L.; Schrumpf, Merry E.; Schwan, Tom G.

    2005-01-01

    Borrelia hermsii is the primary cause of tick-borne relapsing fever in North America. When its tick vector, Ornithodoros hermsi, acquires these spirochetes from the blood of an infected mammal, the bacteria switch their outer surface from one of many bloodstream variable major proteins (Vmps) to a unique protein, Vtp (Vsp33). Vtp may be critical for successful tick transmission of B. hermsii; however, the gene encoding this protein has been described previously in only one isolate. Here we identified and sequenced the vtp gene in 31 isolates of B. hermsii collected over 40 years from localities throughout much of its known geographic distribution. Seven major Vtp types were found. Little or no sequence variation existed within types, but between them significant variation was observed, similar to the pattern of diversity described for the outer surface protein C (OspC) gene in Lyme disease spirochetes. The pattern of sequence relatedness among the Vtp types was incongruent in two branches compared to two genomic groups identified among the isolates by multilocus sequence typing of the 16S rRNA, flaB, gyrB, and glpQ genes. Therefore, both horizontal transfer and recombination within and between the two genomic groups were responsible for some of the variation observed in the vtp gene. O. hermsi ticks were capable of transmitting spirochetes in the newly identified genomic group. Therefore, given the longevity of the tick vector and persistent infection of spirochetes in ticks, these arthropods rather than mammals may be the likely host where the exchange of spirochetal DNA occurs. PMID:16177341

  8. Endemic Foci of the Tick-Borne Relapsing Fever Spirochete Borrelia crocidurae in Mali, West Africa, and the Potential for Human Infection

    PubMed Central

    Schwan, Tom G.; Anderson, Jennifer M.; Lopez, Job E.; Fischer, Robert J.; Raffel, Sandra J.; McCoy, Brandi N.; Safronetz, David; Sogoba, Nafomon; Maïga, Ousmane; Traoré, Sékou F.

    2012-01-01

    Background Tick-borne relapsing fever spirochetes are maintained in endemic foci that involve a diversity of small mammals and argasid ticks in the genus Ornithodoros. Most epidemiological studies of tick-borne relapsing fever in West Africa caused by Borrelia crocidurae have been conducted in Senegal. The risk for humans to acquire relapsing fever in Mali is uncertain, as only a few human cases have been identified. Given the high incidence of malaria in Mali, and the potential to confuse the clinical diagnosis of these two diseases, we initiated studies to determine if there were endemic foci of relapsing fever spirochetes that could pose a risk for human infection. Methodology/Principal Findings We investigated 20 villages across southern Mali for the presence of relapsing fever spirochetes. Small mammals were captured, thin blood smears were examined microscopically for spirochetes, and serum samples were tested for antibodies to relapsing fever spirochetes. Ornithodoros sonrai ticks were collected and examined for spirochetal infection. In total, 11.0% of the 663 rodents and 14.3% of the 63 shrews tested were seropositive and 2.2% of the animals had active spirochete infections when captured. In the Bandiagara region, the prevalence of infection was higher with 35% of the animals seropositive and 10% infected. Here also Ornithodoros sonrai were abundant and 17.3% of 278 individual ticks tested were infected with Borrelia crocidurae. Fifteen isolates of B. crocidurae were established and characterized by multi-locus sequence typing. Conclusions/Significance The potential for human tick-borne relapsing fever exists in many areas of southern Mali. PMID:23209863

  9. Detection and genetic characterization of relapsing fever spirochete Borrelia miyamotoi in Estonian ticks.

    PubMed

    Geller, Julia; Nazarova, Lidia; Katargina, Olga; Järvekülg, Lilian; Fomenko, Natalya; Golovljova, Irina

    2012-01-01

    During the years 2008-2010 I. ricinus and I. persulcatus ticks were collected from 64 sites in mainland Estonia and on the island Saaremaa. Presence of B. miyamotoi was found in 0.9% (23/2622) of ticks. The prevalence in I. persulcatus and I. ricinus ticks differed significantly, 2.7% (15/561) and 0.4% (8/2061), respectively. The highest prevalence rates were in found South-Eastern Estonia in an area of I. persulcatus and I. ricinus sympatry and varied from 1.4% (1/73) to 2.8% (5/178). Co-infections with B. burgdorferi s.l. group spirochetes and tick-borne encephalitis virus were also revealed. Genetic characterization of partial 16S rRNA, p66 and glpQ genes demonstrated that Estonian sequences belong to two types of B. miyamotoi and cluster with sequences from Europe and the European part of Russia, as well as with sequences from Siberia, Asia and Japan, here designated as European and Asian types, respectively. Estonian sequences of the European type were obtained from I. ricinus ticks only, whereas the Asian type of B. miyamotoi was shown for both tick species in the sympatric regions.

  10. Detection and Genetic Characterization of Relapsing Fever Spirochete Borrelia miyamotoi in Estonian Ticks

    PubMed Central

    Geller, Julia; Nazarova, Lidia; Katargina, Olga; Järvekülg, Lilian; Fomenko, Natalya; Golovljova, Irina

    2012-01-01

    During the years 2008–2010 I. ricinus and I. persulcatus ticks were collected from 64 sites in mainland Estonia and on the island Saaremaa. Presence of B. miyamotoi was found in 0.9% (23/2622) of ticks. The prevalence in I. persulcatus and I. ricinus ticks differed significantly, 2.7% (15/561) and 0.4% (8/2061), respectively. The highest prevalence rates were in found South-Eastern Estonia in an area of I. persulcatus and I. ricinus sympatry and varied from 1.4% (1/73) to 2.8% (5/178). Co-infections with B. burgdorferi s.l. group spirochetes and tick-borne encephalitis virus were also revealed. Genetic characterization of partial 16S rRNA, p66 and glpQ genes demonstrated that Estonian sequences belong to two types of B. miyamotoi and cluster with sequences from Europe and the European part of Russia, as well as with sequences from Siberia, Asia and Japan, here designated as European and Asian types, respectively. Estonian sequences of the European type were obtained from I. ricinus ticks only, whereas the Asian type of B. miyamotoi was shown for both tick species in the sympatric regions. PMID:23251652

  11. Periplasmic Flagellar Export Apparatus Protein, FliH, Is Involved in Post-Transcriptional Regulation of FlaB, Motility and Virulence of the Relapsing Fever Spirochete Borrelia hermsii

    PubMed Central

    Guyard, Cyril; Raffel, Sandra J.; Schrumpf, Merry E.; Dahlstrom, Eric; Sturdevant, Daniel; Ricklefs, Stacy M.; Martens, Craig; Hayes, Stanley F.; Fischer, Elizabeth R.; Hansen, Bryan T.; Porcella, Stephen F.; Schwan, Tom G.

    2013-01-01

    Spirochetes are bacteria characterized in part by rotating periplasmic flagella that impart their helical or flat-wave morphology and motility. While most other bacteria rely on a transcriptional cascade to regulate the expression of motility genes, spirochetes employ post-transcriptional mechanism(s) that are only partially known. In the present study, we characterize a spontaneous non-motile mutant of the relapsing fever spirochete Borrelia hermsii that was straight, non-motile and deficient in periplasmic flagella. We used next generation DNA sequencing of the mutant’s genome, which when compared to the wild-type genome identified a 142 bp deletion in the chromosomal gene encoding the flagellar export apparatus protein FliH. Immunoblot and transcription analyses showed that the mutant phenotype was linked to the posttranscriptional deficiency in the synthesis of the major periplasmic flagellar filament core protein FlaB. Despite the lack of FlaB, the amount of FlaA produced by the fliH mutant was similar to the wild-type level. The turnover of the residual pool of FlaB produced by the fliH mutant was comparable to the wild-type spirochete. The non-motile mutant was not infectious in mice and its inoculation did not induce an antibody response. Trans-complementation of the mutant with an intact fliH gene restored the synthesis of FlaB, a normal morphology, motility and infectivity in mice. Therefore, we propose that the flagellar export apparatus protein regulates motility of B. hermsii at the post-transcriptional level by influencing the synthesis of FlaB. PMID:24009690

  12. Relapsing Fever Borreliae: A Global Review.

    PubMed

    Cutler, Sally J

    2015-12-01

    Relapsing fever borreliae were notorious and feared infectious agents that earned their place in history through their devastating impact as causes of both epidemic and endemic infection. They are now considered more as an oddity, and their burden of infection is largely overshadowed by other infections such as malaria, which presents in a similar clinical way. Despite this, they remain the most common bacterial infection in some developing countries. Transmitted by soft ticks or lice, these fascinating spirochetes have evolved a myriad of mechanisms to survive within their diverse environments. PMID:26593261

  13. Characterization of a Novel Relapsing Fever Spirochete in the Midgut, Coxal Fluid, and Salivary Glands of the Bat Tick Carios kelleyi

    PubMed Central

    Raffel, Sandra J.; Schrumpf, Merry E.; Gill, James S.; Piesman, Joseph

    2009-01-01

    Abstract 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 with a Borrelia-specific monoclonal antibody were observed microscopically in the coxal fluid and salivary glands from one tick. These data confirm the presence of a novel species of relapsing fever spirochete in bat ticks and the potential for new enzootic foci for endemic relapsing fever that warrants further investigation. The name Borrelia johnsonii is proposed for this novel spirochete in honor of Dr. Russell C. Johnson. PMID:19281412

  14. Relapsing Fever Spirochetes Retain Infectivity After Prolonged in vitro Cultivation

    PubMed Central

    Schrumpf, Merry E.; Raffel, Sandra J.; Policastro, Paul F.; Porcella, Stephen F.; Schwan, Tom G.

    2008-01-01

    Abstract Borrelia hermsii and Borrelia burgdorferi, two closely related spirochetes, are the etiological agents of tick-borne relapsing fever and Lyme disease, respectively. Previous studies have shown the loss of infectivity of B. burgdorferi is associated with in vitro cultivation. This diminished infectivity of B. burgdorferi has occurred as early as three in vitro passages, and the loss of plasmids have been observed with these less virulent to noninfective cultures. The effects of long-term in vitro cultivation on B. hermsii have not been investigated. However, understanding the degree of genomic degradation during in vitro cultivation is important for investigating pathogenic mechanisms of spirochetes. In this study, we analyzed the effects of continuous in vitro cultivation on the genomic composition and infectivity of B. hermsii and B. turicatae. We report that all seven isolates of B. hermsii and the one isolate of B. turicatae examined retained infectivity in mice after 1 year of continuous in vitro cultivation. Furthermore, there were few apparent differences in the plasmid profiles after long-term cultivation. Two isolates of B. hermsii remained infective after high passage despite losing a portion of the 200-kb linear plasmid containing the fhbA gene encoding the factor H binding protein. Also, sequence analysis of multiple B. hermsii isolates demonstrated two types of fhbA with complete congruence with the two genomic groups of B. hermsii spirochetes. Therefore, these results suggest that relapsing fever spirochetes are genetically stable during in vitro cultivation, and the fhbA-containing segment of DNA that is lost during cultivation is not required for infection. PMID:18637723

  15. Borrelia burgdorferi Spirochetes Induce Mast Cell Activation and Cytokine Release

    PubMed Central

    Talkington, Jeffrey; Nickell, Steven P.

    1999-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, is introduced into human hosts via tick bites. Among the cell types present in the skin which may initially contact spirochetes are mast cells. Since spirochetes are known to activate a variety of cell types in vitro, we tested whether B. burgdorferi spirochetes could activate mast cells. We report here that freshly isolated rat peritoneal mast cells or mouse MC/9 mast cells cultured in vitro with live or freeze-thawed B. burgdorferi spirochetes undergo low but detectable degranulation, as measured by [5-3H] hydroxytryptamine release, and they synthesize and secrete the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In contrast to findings in previous studies, where B. burgdorferi-associated activity was shown to be dependent upon protein lipidation, mast cell TNF-α release was not induced by either lipidated or unlipidated recombinant OspA. This activity was additionally shown to be protease sensitive and surface expressed. Finally, comparisons of TNF-α-inducing activity in known low-, intermediate-, and high-passage B. burgdorferi B31 isolates demonstrated passage-dependent loss of activity, indicating that the activity is probably plasmid encoded. These findings document the presence in low-passage B. burgdorferi spirochetes of a novel lipidation-independent activity capable of inducing cytokine release from host cells. PMID:10024550

  16. Absence of lipopolysaccharide in the Lyme disease spirochete, Borrelia burgdorferi.

    PubMed Central

    Takayama, K; Rothenberg, R J; Barbour, A G

    1987-01-01

    We were unable to demonstrate the presence of the classic enterobacterium-type lipopolysaccharide in the cells of the Lyme disease spirochete, Borrelia burgdorferi B31. This finding was primarily based on chemical analysis and the absence of free lipid A upon mild acid hydrolysis of the appropriate cell extracts. These results do not preclude the possible existence of an unusual lipopolysaccharide-like compound(s) in B. burgdorferi. Images PMID:3623705

  17. Global ecology and epidemiology of Borrelia garinii spirochetes

    PubMed Central

    Comstedt, Pär; Jakobsson, Tobias; Bergström, Sven

    2011-01-01

    Lyme borreliosis (LB) is a tick-transmitted infectious disease caused by Borrelia burgdorferi sensu lato (s. l.). In Europe, three different Borrelia species are the main causative agents of LB: B. burgdorferi sensu stricto (s.s.), Borrelia afzelii, and Borrelia garinii. The latter depends heavily on birds as its main reservoir hosts. In fact, birds can act both as biological carriers of Borrelia and transporters of infected ticks. The seasonal migration of many bird species not only aid in the spread of B. garinii to new foci but also influence the high level of diversity found within this species. B. garinii have been isolated not only from terrestrial birds in Europe, but also from seabirds worldwide, and homology between isolates in these two different infection cycles suggests an overlap and exchange of strains. In addition, it has been shown that birds can maintain and spread B. garinii genotypes associated with LB in humans. This review article discusses the importance of birds in the ecology and epidemiology of B. garinii spirochetes. PMID:22957111

  18. A Novel Surface Antigen of Relapsing Fever Spirochetes Can Discriminate between Relapsing Fever and Lyme Borreliosis▿ † ‡

    PubMed Central

    Lopez, Job E.; Schrumpf, Merry E.; Nagarajan, Vijayaraj; Raffel, Sandra J.; McCoy, Brandi N.; Schwan, Tom G.

    2010-01-01

    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 locus was amplified and sequenced from 39 isolates of B. hermsii that had been acquired from western North America. bipA was also expressed as a recombinant fusion protein. Serum samples from mice and patients infected with B. hermsii or B. burgdorferi were used to confirm the immunogenicity of the recombinant protein in patients infected with relapsing fever spirochetes. Lastly, in silico and experimental analysis indicated that BipA is a surface-exposed lipoprotein in B. hermsii. These findings enhance the capabilities of diagnosing infection with relapsing fever spirochetes. PMID:20147497

  19. Louse-borne relapsing fever (Borrelia recurrentis) in an Eritrean refugee arriving in Switzerland, August 2015.

    PubMed

    Goldenberger, D; Claas, G J; Bloch-Infanger, C; Breidthardt, T; Suter, B; Martínez, M; Neumayr, A; Blaich, A; Egli, A; Osthoff, M

    2015-08-13

    We report an imported case of louse-borne relapsing fever in a young adult Eritrean refugee who presented with fever shortly after arriving in Switzerland. Analysis of blood smears revealed spirochetes identified as Borrelia recurrentis by 16S rRNA gene sequencing. We believe that louse-borne relapsing fever may be seen more frequently in Europe as a consequence of a recent increase in refugees from East Africa travelling to Europe under poor hygienic conditions in confined spaces.

  20. Cotransmission of Divergent Relapsing Fever Spirochetes by Artificially Infected Ornithodoros hermsi▿†

    PubMed Central

    Policastro, Paul F.; Raffel, Sandra J.; Schwan, Tom G.

    2011-01-01

    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 immersion in culture suspensions of several GGI and GGII isolates. We tested for spirochetes in ticks by immunofluorescence microscopy and in mouse blood by quantitative PCR of the vtp locus to differentiate spirochete genotypes. The immersed larval ticks were capable of spirochete transmission to mice at the first nymphal feeding. Tick infection with mixed cultures of isolates DAH (vtp-6) (GGI) and MTW-2 (vtp-5) (GGII) resulted in ticks that caused spirochetemias in mice consisting of MTW-2 or both DAH and MTW-2. These findings show that this soft tick species can acquire B. hermsii by immersion in spirochete suspensions, that GGI and GGII isolates can coinfect the tick vector by this method, and that these spirochetes can be cotransmitted to a rodent host. PMID:21965393

  1. Arthritis severity and spirochete burden are determined by serotype in the Borrelia turicatae-mouse model of Lyme disease.

    PubMed Central

    Pennington, P M; Allred, C D; West, C S; Alvarez, R; Barbour, A G

    1997-01-01

    Immunodeficient mice infected with Borrelia turicatae, a relapsing fever agent, have a disorder that resembles disseminated Lyme disease. Two serotypes, A and B, differed in their arthritogenicity in both CB-17 SCID and C3H SCID mice. In CB-17 SCID mice infected with serotype A or B, arthritis was assessed by measurement of tibiotarsal diameter, functional ability on a beam walk test, and microscopic assessment of joint inflammation. Serotype B-infected mice had greater joint swelling, functional disability, and leukocytic infiltration in the joints than serotype A-infected mice. Joint swelling and disability peaked at 2 weeks of infection and then decreased, while leukocyte infiltration in the joints persisted. To investigate the basis for the differences in arthritogenicity of serotypes A and B, spirochete burdens in infected mice were measured by quantitative PCR of spirochete DNA in joints, direct immunofluorescence of spirochetes in joints, and counts of spirochetes in the blood. At 2 weeks of infection there were seven times more spirochetes in the joints of serotype B-infected mice than in those of serotype A-infected mice, measured by both quantitative PCR and direct enumeration. Although serotypes A and B had the same infectivity and growth rate in vivo, serotype B spirochetes were eightfold more abundant in the blood than serotype A spirochetes and produced greater fatality in newborn mice. These findings indicate that differences in disease severity in mice infected with serotype A or B are attributable to differences in the spirochete burden in the joints and blood. PMID:8975925

  2. Refractoriness of the western fence lizard (Sceloporus occidentalis) to the Lyme disease group spirochete Borrelia bissettii.

    PubMed

    Lane, R S; Mun, J; Eisen, L; Eisen, R J

    2006-08-01

    The western fence lizard, Sceloporus occidentalis, is refractory to experimental infection with Borrelia burgdorferi sensu stricto, one of several Lyme disease spirochetes pathogenic for humans. Another member of the Lyme disease spirochete complex, Borrelia bissettii, is distributed widely throughout North America and a similar, if not identical, spirochete has been implicated as a human pathogen in southern Europe. To determine the susceptibility of S. occidentalis to B. bissettii, 6 naïve lizards were exposed to the feeding activities of Ixodes pacificus nymphs experimentally infected with this spirochete. None of the lizards developed spirochetemias detectable by polymerase chain reaction for up to 8 wk post-tick feeding, infected nymphs apparently lost their B. bissettii infections within 1-2 wk after engorgement, and xenodiagnostic L. pacificus larvae that co-fed alongside infected nymphs did not acquire and maintain spirochetes. In contrast, 3 of 4 naïve deer mice (Peromyscus maniculatus) exposed similarly to feeding by 1 or more B. bissettii-infected nymphs developed patent infections within 4 wk. These and previous findings suggest that the complement system of S. occidentalis typically destroys B. burgdorferi sensu lato spirochetes present in tissues of attached and feeding I. pacificus nymphs, thereby potentially reducing the probability of transmission of these bacteria to humans or other animals by the resultant adult ticks. PMID:16995383

  3. Susceptibility of the western fence lizard (Sceloporus occidentalis) to the Lyme borreliosis spirochete (Borrelia burgdorferi).

    PubMed

    Lane, R S

    1990-01-01

    Attempts to infect juvenile and adult western fence lizards (Sceloporus occidentalis) with the Lyme borreliosis spirochete (Borrelia burgdorferi) were largely unsuccessful. Spirochetes could not be isolated from the blood and various tissues of 14 lizards 21-32 days after they had been inoculated ip (n = 8) or sc (n = 6) with 10(6) or 10(8) B. burgdorferi representing 3 tick isolates, although 1 lizard apparently developed a transitory spirochetemia lasting 2 days. Similarly, spirochetes could not be detected in the blood or tissues of 5 lizards fed upon by 2- greater than 8 infected larvae or nymphs of the western black-legged tick (Ixodes pacificus). Sixty-five blood samples from 59 lizards in an endemic area and various tissues from 20 of the same lizards were also assayed for B. burgdorferi with negative results. The implications of these findings for the maintenance of this spirochete in natural foci are discussed. PMID:2301709

  4. Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the antibiotic Tigecycline

    PubMed Central

    Brorson, Øystein; Brorson, Sverre-Henning; Scythes, John; MacAllister, James; Wier, Andrew; Margulis, Lynn

    2009-01-01

    Persistence of tissue spirochetes of Borrelia burgdorferi as helices and round bodies (RBs) explains many erythema-Lyme disease symptoms. Spirochete RBs (reproductive propagules also called coccoid bodies, globular bodies, spherical bodies, granules, cysts, L-forms, sphaeroplasts, or vesicles) are induced by environmental conditions unfavorable for growth. Viable, they grow, move and reversibly convert into motile helices. Reversible pleiomorphy was recorded in at least six spirochete genera (>12 species). Penicillin solution is one unfavorable condition that induces RBs. This antibiotic that inhibits bacterial cell wall synthesis cures neither the second “Great Imitator” (Lyme borreliosis) nor the first: syphilis. Molecular-microscopic techniques, in principle, can detect in animals (insects, ticks, and mammals, including patients) helices and RBs of live spirochetes. Genome sequences of B. burgdorferi and Treponema pallidum spirochetes show absence of >75% of genes in comparison with their free-living relatives. Irreversible integration of spirochetes at behavioral, metabolic, gene product and genetic levels into animal tissue has been documented. Irreversible integration of spirochetes may severely impair immunological response such that they persist undetected in tissue. We report in vitro inhibition and destruction of B. burgdorferi (helices, RBs = “cysts”) by the antibiotic Tigecycline (TG; Wyeth), a glycylcycline protein-synthesis inhibitor (of both 30S and 70S ribosome subunits). Studies of the pleiomorphic life history stages in response to TG of both B. burgdorferi and Treponema pallidum in vivo and in vitro are strongly encouraged. PMID:19843691

  5. Beta-Amyloid Deposition and Alzheimer's Type Changes Induced by Borrelia Spirochetes

    SciTech Connect

    Miklossy,J.; Kis, A.; Radenovic, A.; Miller, L.; Forro, L.; Martins, R.; Reiss, K.; Darbinian, N.; Darekar, P.; et al.

    2006-01-01

    The pathological hallmarks of Alzheimer's disease (AD) consist of {beta}-amyloid plaques and neurofibrillary tangles in affected brain areas. The processes, which drive this host reaction are unknown. To determine whether an analogous host reaction to that occurring in AD could be induced by infectious agents, we exposed mammalian glial and neuronal cells in vitro to Borrelia burgdorferi spirochetes and to the inflammatory bacterial lipopolysaccharide (LPS). Morphological changes analogous to the amyloid deposits of AD brain were observed following 2-8 weeks of exposure to the spirochetes. Increased levels of {beta}-amyloid presursor protein (A{beta}PP) and hyperphosphorylated tau were also detected by Western blots of extracts of cultured cells that had been treated with spirochetes or LPS. These observations indicate that, by exposure to bacteria or to their toxic products, host responses similar in nature to those observed in AD may be induced.

  6. Tick-borne Relapsing Fever and Borrelia hermsii, Los Angeles County, California, USA

    PubMed Central

    Raffel, Sandra J.; Schrumpf, Merry E.; Webster, Larry S.; Marques, Adriana R.; Spano, Robyn; Rood, Michael; Burns, Joe; Hu, Renjie

    2009-01-01

    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 showed the presence of O. hermsi ticks infected with B. hermsii and the presence of rodents that were seropositive for the spirochete. We determined that this tick-borne disease is endemic to the San Gabriel Mountains near the greater Los Angeles metropolitan area. PMID:19624916

  7. TLR1/TLR2 heterodimers play an important role in the recognition of Borrelia spirochetes.

    PubMed

    Oosting, Marije; Ter Hofstede, Hadewych; Sturm, Patrick; Adema, Gosse J; Kullberg, Bart-Jan; van der Meer, Jos W M; Netea, Mihai G; Joosten, Leo A B

    2011-01-01

    After infection with Borrelia species, the risk for developing Lyme disease varies significantly between individuals. Recognition of Borrelia by the immune system is mediated by pattern recognition receptors (PRRs), such as TLRs. While TLR2 is the main recognition receptor for Borrelia spp., little is known about the role of TLR1 and TLR6, which both can form functionally active heterodimers with TLR2. Here we investigated the recognition of Borrelia by both murine and human TLR1 and TLR6. Peritoneal macrophages from TLR1- and TLR6- gene deficient mice were isolated and exposed to Borrelia. Human PBMCs were stimulated with Borrelia with or without specific TLR1 and TLR6 blocking using specific antibodies. Finally, the functional consequences of TLR polymorphisms on Borrelia-induced cytokine production were assessed. Splenocytes isolated from both TLR1-/- and TLR6-/- mice displayed a distorted Th1/Th2 cytokine balance after stimulation with B.burgdorferi, while no differences in pro-inflammatory cytokine production were observed. In contrast, blockade of TLR1 with specific neutralizing antibodies led to decreased cytokine production by human PBMCs after exposure to B.burgdorferi. Blockade of human TLR6 did not lead to suppression of cytokine production. When PBMCs from healthy individuals bearing polymorphisms in TLR1 were exposed to B.burgdorferi, a remarkably decreased in vitro cytokine production was observed in comparison to wild-type controls. TLR6 polymorphisms lead to a minor modified cytokine production. This study indicates a dominant role for TLR1/TLR2 heterodimers in the induction of the early inflammatory response by Borrelia spirochetes in humans. PMID:21998742

  8. Hypothetical Protein BB0569 Is Essential for Chemotaxis of the Lyme Disease Spirochete Borrelia burgdorferi

    PubMed Central

    Zhang, Kai; Liu, Jun; Charon, Nyles W.

    2015-01-01

    ABSTRACT The Lyme disease spirochete Borrelia burgdorferi has five putative methyl-accepting chemotaxis proteins (MCPs). In this report, we provide evidence that a hypothetical protein, BB0569, is essential for the chemotaxis of B. burgdorferi. While BB0569 lacks significant homology to the canonical MCPs, it contains a conserved domain (spanning residues 110 to 170) that is often evident in membrane-bound MCPs such as Tar and Tsr of Escherichia coli. Unlike Tar and Tsr, BB0569 lacks transmembrane regions and recognizable HAMP and methylation domains and is similar to TlpC, a cytoplasmic chemoreceptor of Rhodobacter sphaeroides. An isogenic mutant of BB0569 constantly runs in one direction and fails to respond to attractants, indicating that BB0569 is essential for chemotaxis. Immunofluorescence, green fluorescent protein (GFP) fusion, and cryo-electron tomography analyses demonstrate that BB0569 localizes at the cell poles and is required for chemoreceptor clustering at the cell poles. Protein cross-linking studies reveal that BB0569 forms large protein complexes with MCP3, indicative of its interactions with other MCPs. Interestingly, analysis of B. burgdorferi mcp mutants shows that inactivation of either mcp2 or mcp3 reduces the level of BB0569 substantially and that such a reduction is caused by protein turnover. Collectively, these results demonstrate that the domain composition and function of BB0569 are similar in some respects to those of TlpC but that these proteins are different in their cellular locations, further highlighting that the chemotaxis of B. burgdorferi is unique and different from the Escherichia coli and Salmonella enterica paradigm. IMPORTANCE Spirochete chemotaxis differs substantially from the Escherichia coli and Salmonella enterica paradigm, and the basis for controlling the rotation of the bundles of periplasmic flagella at each end of the cell is unknown. In recent years, Borrelia burgdorferi, the causative agent of Lyme disease, has

  9. Serodiagnosis of Louse-Borne Relapsing Fever with Glycerophosphodiester Phosphodiesterase (GlpQ) from Borrelia recurrentis

    PubMed Central

    Porcella, Stephen F.; Raffel, Sandra J.; Schrumpf, Merry E.; Schriefer, Martin E.; Dennis, David T.; Schwan, Tom G.

    2000-01-01

    Human louse-borne relapsing fever occurs in sporadic outbreaks in central and eastern Africa that are characterized by significant morbidity and mortality. Isolates of the causative agent, Borrelia recurrentis, were obtained from the blood of four patients during a recent epidemic of the disease in southern Sudan. The glpQ gene, encoding glycerophosphodiester phosphodiesterase, from these isolates was sequenced and compared with the glpQ sequences obtained from other relapsing-fever spirochetes. Previously we showed that GlpQ of Borrelia hermsii is an immunogenic protein with utility as a serological test antigen for discriminating tick-borne relapsing fever from Lyme disease. In the present work, we cloned and expressed the glpQ gene from B. recurrentis and used recombinant GlpQ in serological tests. Acute- and convalescent-phase serum samples obtained from 42 patients with louse-borne relapsing fever were tested with an indirect immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) that used whole cells of B. recurrentis and with immunoblotting to whole-cell lysates of the spirochete and Escherichia coli producing recombinant GlpQ. The geometric mean titers of the acute- and convalescent-phase serum samples measured by IFA were 1:83 and 1:575, respectively. The immunoblot analysis identified a high level of reactivity and seroconversion to GlpQ, and the assay was more sensitive than the whole-cell IFA and ELISA using purified, recombinant histidine-tagged GlpQ. Serum antibodies to GlpQ and other antigens persisted for 27 years in one patient. We conclude that assessment of anti-GlpQ antibodies will allow serological confirmation of louse-borne relapsing fever and determination of disease prevalence. PMID:11015364

  10. Use of T7 RNA polymerase to direct expression of outer Surface Protein A (OspA) from the Lyme disease Spirochete, Borrelia burgdorferi

    NASA Technical Reports Server (NTRS)

    Dunn, John J.; Lade, Barbara N.

    1991-01-01

    The OspA gene from a North American strain of the Lyme disease Spirochete, Borrelia burgdorferi, was cloned under the control of transciption and translation signals from bacteriophage T7. Full-length OspA protein, a 273 amino acid (31kD) lipoprotein, is expressed poorly in Escherichia coli and is associated with the insoluble membrane fraction. In contrast, a truncated form of OspA lacking the amino-terminal signal sequence which normally would direct localization of the protein to the outer membrane is expressed at very high levels (less than or equal to 100 mg/liter) and is soluble. The truncated protein was purified to homogeneity and is being tested to see if it will be useful as an immunogen in a vaccine against Lyme disease. Circular dichroism and fluorescence spectroscopy was used to characterize the secondary structure and study conformational changes in the protein. Studies underway with other surface proteins from B burgdorferi and a related spirochete, B. hermsii, which causes relapsing fever, leads us to conclude that a strategy similar to that used to express the truncated OspA can provide a facile method for producing variations of Borrelia lipoproteins which are highly expressed in E. coli and soluble without exposure to detergents.

  11. Reservoir competence of Microtus pennsylvanicus (Rodentia: Cricetidae) for the Lyme disease spirochete, Borrelia burgdorferi

    USGS Publications Warehouse

    Markowski, D.; Ginsberg, H.S.; Hyland, K.E.; Hu, R.

    1998-01-01

    The reservoir competence of the meadow vole, Microtus pennsylvanicus Ord, for the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner was established on Patience Island, RI. Meadow voles were collected from 5 locations throughout Rhode Island. At 4 of the field sites, M. pennsylvanicus represented only 4.0% (n = 141) of the animals captured. However, on Patience Island, M. pennsylvanicus was the sole small mammal collected (n = 48). Of the larval Ixodes scapularis Say obtained from the meadow voles on Patience Island, 62% (n = 78) was infected with B. burgdorferi. Meadow voles from all 5 locations were successfully infected with B. burgdorferi in the laboratory and were capable of passing the infection to xenodiagnostic I. scapularis larvae for 9 wk. We concluded that M. pennsylvanicus was physiologically capable of maintaining B. burgdorferi infection. However, in locations where Peromyscus leucopus (Rafinesque) is abundant, the role of M. pennsylvanicus as a primary reservoir for B. burgdorferi was reduced.

  12. Spotted fever group rickettsiae or Borrelia burgdorferi in Ixodes cookei (Ixodidae) in Connecticut.

    PubMed Central

    Magnarelli, L A; Swihart, R K

    1991-01-01

    Immatures and females of Ixodes cookei, a hard-bodied tick, were collected from woodchucks and other mammals in the northeastern United States and examined for spotted fever group rickettsiae and Borrelia burgdorferi. Of the 93 nymphs analyzed by a hemolymph test, 4 (4.3%) harbored rickettsiae. Six (15%) of 40 females were also infected. All infected ticks were collected from woodchucks in Connecticut. Indirect fluorescent antibody staining of midgut tissues from 128 nymphs revealed B. burgdorferi in two (1.6%) ticks, whereas larval and female ticks were negative. Further consideration should be given to I. cookei as a possible vector of spotted fever group rickettsiae or spirochetes that cause Lyme borreliosis. PMID:1885748

  13. Distribution and molecular analysis of Lyme disease spirochetes, Borrelia burgdorferi, isolated from ticks throughout California.

    PubMed Central

    Schwan, T G; Schrumpf, M E; Karstens, R H; Clover, J R; Wong, J; Daugherty, M; Struthers, M; Rosa, P A

    1993-01-01

    Previous studies describing the occurrence and molecular characteristics of Lyme disease spirochetes, Borrelia burgdorferi, from California have been restricted primarily to isolates obtained from the north coastal region of this large and ecologically diverse state. Our objective was to look for and examine B. burdorferi organisms isolated from Ixodes pacificus ticks collected from numerous regions spanning most parts of California where this tick is found. Thirty-one isolates of B. burgdorferi were examined from individual or pooled I. pacificus ticks collected from 25 counties throughout the state. One isolate was obtained from ticks collected at Wawona Campground in Yosemite National Park, documenting the occurrence of the Lyme disease spirochete in an area of intensive human recreational use. One isolate from an Ixodes neotomae tick from an additional county was also examined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot analysis, agarose gel electrophoresis, Southern blot analysis, and the polymerase chain reaction were used to examine the molecular and genetic determinants of these uncloned, low-passage-number isolates. All of the isolates were identified as B. burgdorferi by their protein profiles and reactivities with monoclonal and polyclonal antibodies, and all the isolates were typed by the polymerase chain reaction as North American-type spirochetes (B. burgdorferi sensu stricto). Although products of the ospAB locus were identified in protein analyses in all of the isolates, several isolates contained deleted forms of this locus that would result in the expression of chimeric OspA-OspB proteins. The analysis of OspC demonstrated that this protein was widely conserved among the isolates but was also quite variable in its molecular mass and the amount of it that was expressed. Images PMID:8308101

  14. Genetic control of the innate immune response to Borrelia hermsii influences the course of relapsing fever in inbred strains of mice.

    PubMed

    Benoit, Vivian M; Petrich, Annett; Alugupalli, Kishore R; Marty-Roix, Robin; Moter, Annette; Leong, John M; Boyartchuk, Victor L

    2010-02-01

    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 susceptibility to Borrelia hermsii infection, we performed a systematic analysis of the course of infection using immunocompetent and immunocompromised inbred strains of mice. Our analysis revealed that sensitivity to B. hermsii infections is genetically controlled. In addition, whereas the role of adaptive immunity to relapsing fever-causing spirochetes is well documented, we found that innate immunity contributes significantly to the reduction of bacterial burden. Similar to human infection, the progression of the disease in mice was associated with thrombocytopenia and anemia. Histological and fluorescence in situ hybridization (FISH) analysis of infected tissues indicated that red blood cells (RBCs) were removed by tissue-resident macrophages, a process that could lead to anemia. Spirochetes in the spleen and liver were often visualized associated with RBCs, lending support to the hypothesis that direct interaction of B. hermsii spirochetes with RBCs leads to clearance of bacteria from the bloodstream by tissue phagocytes. PMID:19995898

  15. Neutrophil extracellular traps entrap and kill Borrelia burgdorferi sensu stricto spirochetes and are not affected by Ixodes ricinus tick saliva.

    PubMed

    Menten-Dedoyart, Catherine; Faccinetto, Céline; Golovchenko, Maryna; Dupiereux, Ingrid; Van Lerberghe, Pierre-Bernard; Dubois, Sophie; Desmet, Christophe; Elmoualij, Benaissa; Baron, Frédéric; Rudenko, Nataliia; Oury, Cécile; Heinen, Ernst; Couvreur, Bernard

    2012-12-01

    Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. They are transmitted mainly by Ixodes ricinus ticks. After a few hours of infestation, neutrophils massively infiltrate the bite site. They can kill Borrelia via phagocytosis, oxidative burst, and hydrolytic enzymes. However, factors in tick saliva promote propagation of the bacteria in the host even in the presence of a large number of neutrophils. The neutrophil extracellular trap (NET) consists in the extrusion of the neutrophil's own DNA, forming traps that can retain and kill bacteria. The production of reactive oxygen species is apparently associated with the onset of NETs (NETosis). In this article, we describe NET formation at the tick bite site in vivo in mice. We show that Borrelia burgdorferi sensu stricto spirochetes become trapped and killed by NETs in humans and that the bacteria do not seem to release significant nucleases to evade this process. Saliva from I. ricinus did not affect NET formation by human neutrophils or its stability. However, it greatly decreased neutrophil reactive oxygen species production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation. Finally, round bodies trapped in NETs were observed, some of them staining as live bacteria. This observation could help contribute to a better understanding of the early steps of Borrelia invasion and erythema migrans formation after tick bite. PMID:23109724

  16. Complex Population Structure of Lyme Borreliosis Group Spirochete Borrelia garinii in Subarctic Eurasia

    PubMed Central

    Comstedt, Pär; Asokliene, Loreta; Eliasson, Ingvar; Olsen, Björn; Wallensten, Anders; Bunikis, Jonas; Bergström, Sven

    2009-01-01

    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 of representative collections of this spirochete's samples, as well as of the lack of reliable measure of the genetic heterogeneity of its strains. As a prerequisite for understanding the epidemiological correlates of the complex maintenance of B. garinii, the present study sought to assess the diversity and phylogenetic relationships of this species' strains from its natural hosts and patients with Lyme borreliosis from subarctic Eurasia. We used sequence typing of the partial rrs-rrl intergenic spacer (IGS) of archived and prospective samples of B. garinii from I. uriae ticks collected predominantly on Commander Islands in North Pacific, as well as on the islands in northern Sweden and arctic Norway. We also typed B. garinii samples from patients with Lyme borreliosis and I. ricinus ticks infesting migratory birds in southern Sweden, or found questing in selected sites on the islands in the Baltic Sea and Lithuania. Fifty-two (68%) of 77 B. garinii samples representing wide geographical range and associated with I. ricinus and infection of humans contributed 12 (60%) of total 20 identified IGS variants. In contrast, the remaining 25 (32%) samples recovered from I. uriae ticks from a few islands accounted for as many as 10 (50%) IGS types, suggesting greater local diversity of B. garinii maintained by seabirds and their ticks. Two IGS variants of the spirochete in common for both tick species were found in I. ricinus larvae from migratory birds, an indication that B

  17. Reservoir competence of native North American birds for the Lyme disease spirochete, Borrelia burgdorferi

    USGS Publications Warehouse

    Ginsberg, H.S.; Buckley, P.A.; Balmforth, M.G.; Zhioua, E.; Mitra, Siddhartha; Buckley, F.G.

    2005-01-01

    Reservoir competence of the Lyme disease spirochete, Borrelia burgdorferi, was tested for six species of native North American birds: American Robin, Gray Catbird, Brown Thrasher, Eastern Towhee, Song Sparrow, and Northern Cardinal. Wild birds collected by mistnetting on Fire Island, NY, were held in a field lab in cages over water, and locally collected larval ticks were placed on the birds, harvested from the water after engorgement, and tested for infection by DFA after molting to the nymphal stage. American Robins were competent reservoirs, infecting 16.1% of larvae applied to wild-caught birds, compared to 0% of control ticks placed on uninfected lab mice. Robins that were previously infected in the lab by nymphal feeding infected 81.8% of applied larvae. Wild-caught Song Sparrows infected 4.8% of applied larvae, and 21.1% when infected by nymphal feeding. Results suggest moderate levels of reservoir competence for Northern Cardinals, lower levels for Gray Catbirds, and little evidence of reservoir competence for Eastern Towhees or Brown Thrashers. Lower infection rates in larvae applied to wild-caught birds compared to birds infected in the lab suggest that infected birds display temporal variability in infectiousness to larval ticks. Engorged larvae drop from birds abundantly during daylight hours, so the abundance of these bird species in the peridomestic environment suggests that they might contribute infected ticks to lawns and gardens.

  18. The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi.

    PubMed

    Novak, Elizabeth A; Sultan, Syed Z; Motaleb, Md A

    2014-01-01

    In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease.

  19. Novel relapsing fever Borrelia detected in African penguins (Spheniscus demersus) admitted to two rehabilitation centers in South Africa.

    PubMed

    Yabsley, Michael J; Parsons, Nola J; Horne, Elizabeth C; Shock, Barbara C; Purdee, Michaelle

    2012-03-01

    The African penguin, Spheniscus demersus, the only penguin species that breeds in Africa, is endangered, and several diseases including avian malaria, babesiosis, and aspergillosis are common in some populations. From 2002 to 2010, spirochetes morphologically consistent with Borrelia were observed on thin blood smears from 115 of 8,343 (1.4%) African penguins admitted to rehabilitation centers in the Western Cape and Eastern Cape provinces of South Africa. Prevalence rates were significantly higher among chicks and juveniles compared with adults and for birds sampled during the summer months of October to February compared with winter months. The majority of infected birds were ultimately released, despite lack of antibiotic treatment; however, at least one bird is believed to have died of borreliosis based on characteristic gross and microscopic lesions. Analysis of partial flaB gene sequences indicated this was a relapsing fever Borrelia most similar to a Borrelia sp. detected in soft ticks from a seabird colony in Japan. This represents the fourth report of a relapsing fever Borrelia sp. in an avian species and highlights the need for additional studies of potentially pathogenic organisms infecting the African penguin in South Africa. PMID:21870246

  20. Novel relapsing fever Borrelia detected in African penguins (Spheniscus demersus) admitted to two rehabilitation centers in South Africa.

    PubMed

    Yabsley, Michael J; Parsons, Nola J; Horne, Elizabeth C; Shock, Barbara C; Purdee, Michaelle

    2012-03-01

    The African penguin, Spheniscus demersus, the only penguin species that breeds in Africa, is endangered, and several diseases including avian malaria, babesiosis, and aspergillosis are common in some populations. From 2002 to 2010, spirochetes morphologically consistent with Borrelia were observed on thin blood smears from 115 of 8,343 (1.4%) African penguins admitted to rehabilitation centers in the Western Cape and Eastern Cape provinces of South Africa. Prevalence rates were significantly higher among chicks and juveniles compared with adults and for birds sampled during the summer months of October to February compared with winter months. The majority of infected birds were ultimately released, despite lack of antibiotic treatment; however, at least one bird is believed to have died of borreliosis based on characteristic gross and microscopic lesions. Analysis of partial flaB gene sequences indicated this was a relapsing fever Borrelia most similar to a Borrelia sp. detected in soft ticks from a seabird colony in Japan. This represents the fourth report of a relapsing fever Borrelia sp. in an avian species and highlights the need for additional studies of potentially pathogenic organisms infecting the African penguin in South Africa.

  1. Lyme disease and relapsing fever Borrelia elongate through zones of peptidoglycan synthesis that mark division sites of daughter cells.

    PubMed

    Jutras, Brandon Lyon; Scott, Molly; Parry, Bradley; Biboy, Jacob; Gray, Joe; Vollmer, Waldemar; Jacobs-Wagner, Christine

    2016-08-16

    Agents that cause Lyme disease, relapsing fever, leptospirosis, and syphilis belong to the phylum Spirochaetae-a unique lineage of bacteria most known for their long, spiral morphology. Despite the relevance to human health, little is known about the most fundamental aspects of spirochete growth. Here, using quantitative microscopy to track peptidoglycan cell-wall synthesis, we found that the Lyme disease spirochete Borrelia burgdorferi displays a complex pattern of growth. B. burgdorferi elongates from discrete zones that are both spatially and temporally regulated. In addition, some peptidoglycan incorporation occurs along the cell body, with the notable exception of a large region at the poles. Newborn cells inherit a highly active zone of peptidoglycan synthesis at midcell that contributes to elongation for most of the cell cycle. Concomitant with the initiation of nucleoid separation and cell constriction, second and third zones of elongation are established at the 1/4 and 3/4 cellular positions, marking future sites of division for the subsequent generation. Positioning of elongation zones along the cell is robust to cell length variations and is relatively precise over long distances (>30 µm), suggesting that cells ‟sense" relative, as opposed to absolute, cell length to establish zones of peptidoglycan synthesis. The transition from one to three zones of peptidoglycan growth during the cell cycle is also observed in relapsing fever Borrelia. However, this mode of growth does not extend to representative species from other spirochetal genera, suggesting that this distinctive growth mode represents an evolutionary divide in the spirochete phylum. PMID:27506799

  2. Blood-Borne Candidatus Borrelia algerica in a Patient with Prolonged Fever in Oran, Algeria.

    PubMed

    Fotso Fotso, Aurélien; Angelakis, Emmanouil; Mouffok, Nadjet; Drancourt, Michel; Raoult, Didier

    2015-11-01

    To improve the knowledge base of Borrelia in north Africa, we tested 257 blood samples collected from febrile patients in Oran, Algeria, between January and December 2012 for Borrelia species using flagellin gene polymerase chain reaction sequencing. A sequence indicative of a new Borrelia sp. named Candidatus Borrelia algerica was detected in one blood sample. Further multispacer sequence typing indicated this Borrelia sp. had 97% similarity with Borrelia crocidurae, Borrelia duttonii, and Borrelia recurrentis. In silico comparison of Candidatus B. algerica spacer sequences with those of Borrelia hispanica and Borrelia garinii revealed 94% and 89% similarity, respectively. Candidatus B. algerica is a new relapsing fever Borrelia sp. detected in Oran. Further studies may help predict its epidemiological importance.

  3. Distribution of the Lyme Disease Spirochete Borrelia burgdorferi in Naturally and Experimentally Infected Western Gray Squirrels (Sciurus griseus)

    PubMed Central

    Jensen, Kelly; Salkeld, Daniel J.; Lane, Robert S.

    2010-01-01

    Abstract The dynamics of Borrelia burgdorferi infections within its natural hosts are poorly understood. We necropsied four wild-caught western gray squirrels (Sciurus griseus) that were acquired during a previous study that evaluated the reservoir competence of this rodent for the Lyme disease spirochete. One animal was infected experimentally, whereas the others were infected in the wild before capture. To investigate dissemination of B. burgdorferi and concurrent histopathologic lesions in different tissues, blood specimens, synovial and cerebrospinal fluid, ear-punch biopsies, and diverse tissue samples from skin and various organs were taken and examined by culture, polymerase chain reaction, and histology. Borrelia-positive cultures were obtained from three of the squirrels, that is, from skin biopsies (7 of 20 samples), ear-punch biopsies (2 of 8), and one (1 of 5) lymph node. Sequencing of amplicons confirmed B. burgdorferi sensu stricto (s.s.) infection in 9 of 10 culture-positive samples and in DNA extracted from all 10 positive cultures. The experimentally infected squirrel yielded most of the positive samples. In contrast, bodily fluids, all other organ specimens from these animals, and all samples from one naturally infected squirrel were negative for Borrelia for both assays. None of the necropsied squirrels exhibited specific clinical signs associated with B. burgdorferi. Similarly, necropsy and histological examination of tissues indicated the presence of underlying infectious processes, none of which could be ascribed conclusively to B. burgdorferi infection. Based on these results, obtained from a small number of animals investigated at a single time point, we suggest that B. burgdorferi s.s. infection in S. griseus may result in rather localized dissemination of spirochetes, and that mild or nonclinical disease might be more common after several months of infection duration. Since spirochetes could be detected in squirrels 7–21 months

  4. Borrelia burgdorferi Sensu Lato Spirochetes in Wild Birds in Northwestern California: Associations with Ecological Factors, Bird Behavior and Tick Infestation

    PubMed Central

    Newman, Erica A.; Eisen, Lars; Eisen, Rebecca J.; Fedorova, Natalia; Hasty, Jeomhee M.; Vaughn, Charles; Lane, Robert S.

    2015-01-01

    Although Borrelia burgdorferi sensu lato (s.l.) are found in a great diversity of vertebrates, most studies in North America have focused on the role of mammals as spirochete reservoir hosts. We investigated the roles of birds as hosts for subadult Ixodes pacificus ticks and potential reservoirs of the Lyme disease spirochete B. burgdorferi sensu stricto (s.s.) in northwestern California. Overall, 623 birds representing 53 species yielded 284 I. pacificus larvae and nymphs. We used generalized linear models and zero-inflated negative binomial models to determine associations of bird behaviors, taxonomic relationships and infestation by I. pacificus with borrelial infection in the birds. Infection status in birds was best explained by taxonomic order, number of infesting nymphs, sampling year, and log-transformed average body weight. Presence and counts of larvae and nymphs could be predicted by ground- or bark-foraging behavior and contact with dense oak woodland. Molecular analysis yielded the first reported detection of Borrelia bissettii in birds. Moreover, our data suggest that the Golden-crowned Sparrow (Zonotrichia atricapilla), a non-resident species, could be an important reservoir for B. burgdorferi s.s. Of 12 individual birds (9 species) that carried B. burgdorferi s.l.-infected larvae, no birds carried the same genospecies of B. burgdorferi s.l. in their blood as were present in the infected larvae removed from them. Possible reasons for this discrepancy are discussed. Our study is the first to explicitly incorporate both taxonomic relationships and behaviors as predictor variables to identify putative avian reservoirs of B. burgdorferi s.l. Our findings underscore the importance of bird behavior to explain local tick infestation and Borrelia infection in these animals, and suggest the potential for bird-mediated geographic spread of vector ticks and spirochetes in the far-western United States. PMID:25714376

  5. Borrelia burgdorferi sensu lato spirochetes in wild birds in northwestern California: associations with ecological factors, bird behavior and tick infestation.

    PubMed

    Newman, Erica A; Eisen, Lars; Eisen, Rebecca J; Fedorova, Natalia; Hasty, Jeomhee M; Vaughn, Charles; Lane, Robert S

    2015-01-01

    Although Borrelia burgdorferi sensu lato (s.l.) are found in a great diversity of vertebrates, most studies in North America have focused on the role of mammals as spirochete reservoir hosts. We investigated the roles of birds as hosts for subadult Ixodes pacificus ticks and potential reservoirs of the Lyme disease spirochete B. burgdorferi sensu stricto (s.s.) in northwestern California. Overall, 623 birds representing 53 species yielded 284 I. pacificus larvae and nymphs. We used generalized linear models and zero-inflated negative binomial models to determine associations of bird behaviors, taxonomic relationships and infestation by I. pacificus with borrelial infection in the birds. Infection status in birds was best explained by taxonomic order, number of infesting nymphs, sampling year, and log-transformed average body weight. Presence and counts of larvae and nymphs could be predicted by ground- or bark-foraging behavior and contact with dense oak woodland. Molecular analysis yielded the first reported detection of Borrelia bissettii in birds. Moreover, our data suggest that the Golden-crowned Sparrow (Zonotrichia atricapilla), a non-resident species, could be an important reservoir for B. burgdorferi s.s. Of 12 individual birds (9 species) that carried B. burgdorferi s.l.-infected larvae, no birds carried the same genospecies of B. burgdorferi s.l. in their blood as were present in the infected larvae removed from them. Possible reasons for this discrepancy are discussed. Our study is the first to explicitly incorporate both taxonomic relationships and behaviors as predictor variables to identify putative avian reservoirs of B. burgdorferi s.l. Our findings underscore the importance of bird behavior to explain local tick infestation and Borrelia infection in these animals, and suggest the potential for bird-mediated geographic spread of vector ticks and spirochetes in the far-western United States.

  6. Divergence of Borrelia burgdorferi sensu lato spirochetes could be driven by the host: diversity of Borrelia strains isolated from ticks feeding on a single bird

    PubMed Central

    2014-01-01

    Background The controversy surrounding the potential impact of birds in spirochete transmission dynamics and their capacity to serve as a reservoir has existed for a long time. The majority of analyzed bird species are able to infect larval ticks with Borrelia. Dispersal of infected ticks due to bird migration is a key to the establishment of new foci of Lyme borreliosis. The dynamics of infection in birds supports the mixing of different species, the horizontal exchange of genetic information, and appearance of recombinant genotypes. Methods Four Borrelia burgdorferi sensu lato strains were cultured from Ixodes minor larvae and four strains were isolated from Ixodes minor nymphs collected from a single Carolina Wren (Thryothorus ludovicianus). A multilocus sequence analysis that included 16S rRNA, a 5S-23S intergenic spacer region, a 16S-23S internal transcribed spacer, flagellin, p66, and ospC separated 8 strains into 3 distinct groups. Additional multilocus sequence typing of 8 housekeeping genes, clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA was used to resolve the taxonomic status of bird-associated strains. Results Results of analysis of 14 genes confirmed that the level of divergence among strains is significantly higher than what would be expected for strains within a single species. The presence of cross-species recombination was revealed: Borrelia burgdorferi sensu stricto housekeeping gene nifS was incorporated into homologous locus of strain, previously assigned to B. americana. Conclusions Genetically diverse Borrelia strains are often found within the same tick or same vertebrate host, presenting a wide opportunity for genetic exchange. We report the cross-species recombination that led to incorporation of a housekeeping gene from the B. burgdorferi sensu stricto strain into a homologous locus of another bird-associated strain. Our results support the hypothesis that recombination maintains a majority of sequence polymorphism within Borrelia

  7. The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia

    PubMed Central

    2013-01-01

    Background Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi, affects both the peripheral and the central nervous systems. Radiculitis or nerve root inflammation, which can cause pain, sensory loss, and weakness, is the most common manifestation of peripheral LNB in humans. We previously reported that rhesus monkeys infected with B. burgdorferi develop radiculitis as well as inflammation in the dorsal root ganglia (DRG), with elevated levels of neuronal and satellite glial cell apoptosis in the DRG. We hypothesized that B. burgdorferi induces inflammatory mediators in glial and neuronal cells and that this inflammatory milieu precipitates glial and neuronal apoptosis. Methods To model peripheral neuropathy in LNB we incubated normal rhesus DRG tissue explants with live B. burgdorferi ex vivo and identified immune mediators, producer cells, and verified the presence of B. burgdorferi in tissue sections by immunofluorescence staining and confocal microscopy. We also set up primary cultures of DRG cells from normal adult rhesus macaques and incubated the cultures with live B. burgdorferi. Culture supernatants were subjected to multiplex ELISA to detect immune mediators, while the cells were evaluated for apoptosis by the in situ TUNEL assay. A role for inflammation in mediating apoptosis was assessed by evaluating the above phenomena in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone. As Schwann cells ensheath the dorsal roots of the DRG, we evaluated the potential of live B. burgdorferi to induce inflammatory mediators in human Schwann cell (HSC) cultures. Results Rhesus DRG tissue explants exposed to live B. burgdorferi showed localization of CCL2 and IL-6 in sensory neurons, satellite glial cells and Schwann cells while IL-8 was seen in satellite glial cells and Schwann cells. Live B. burgdorferi induced elevated levels of IL-6, IL-8 and CCL2 in HSC and DRG cultures and apoptosis of sensory

  8. Large linear plasmids of Borrelia species that cause relapsing fever.

    PubMed

    Miller, Shelley Campeau; Porcella, Stephen F; Raffel, Sandra J; Schwan, Tom G; Barbour, Alan G

    2013-08-01

    Borrelia species of relapsing fever (RF) and Lyme disease (LD) lineages have linear chromosomes and both linear and circular plasmids. Unique to RF species, and little characterized to date, are large linear plasmids of ∼160 kb, or ∼10% of the genome. By a combination of Sanger and next-generation methods, we determined the sequences of large linear plasmids of two New World species: Borrelia hermsii, to completion of its 174-kb length, and B. turicatae, partially to 114 kb of its 150 kb. These sequences were then compared to corresponding sequences of the Old World species B. duttonii and B. recurrentis and to plasmid sequences of LD Borrelia species. The large plasmids were largely colinear, except for their left ends, about 27 kb of which was inverted in New World species. Approximately 60% of the B. hermsii lp174 plasmid sequence was repetitive for 6 types of sequence, and half of its open reading frames encoded hypothetical proteins not discernibly similar to proteins in the database. The central ∼25 kb of all 4 linear plasmids was syntenic for orthologous genes for plasmid maintenance or partitioning in Borrelia species. Of all the sequenced linear and circular plasmids in Borrelia species, the large plasmid's putative partition/replication genes were most similar to those of the 54-kb linear plasmids of LD species. Further evidence for shared ancestry was the observation that two of the hypothetical proteins were predicted to be structurally similar to the LD species' CspA proteins, which are encoded on the 54-kb plasmids.

  9. Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia

    PubMed Central

    Toledo, Alvaro; Monzón, Javier D.; Coleman, James L.; Garcia-Monco, Juan C.; Benach, Jorge L.

    2015-01-01

    The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease. PMID:25870274

  10. Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia.

    PubMed

    Toledo, Alvaro; Monzón, Javier D; Coleman, James L; Garcia-Monco, Juan C; Benach, Jorge L

    2015-04-28

    The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.

  11. OspA immunization decreases transmission of Borrelia burgdorferi spirochetes from infected Peromyscus leucopus mice to larval Ixodes scapularis ticks.

    PubMed

    Tsao, J; Barbour, A G; Luke, C J; Fikrig, E; Fish, D

    2001-01-01

    Recombinant outer surface protein A (OspA) vaccination of wild animal reservoirs has potential application for reducing Borrelia burgdorferi transmission in nature and subsequent risk of human infection. As a major reservoir host, the white-footed mouse (Peromyscus leucopus) is a candidate for a vaccination program designed to reduce infection prevalence in vector ticks. In this study we characterized the effect of various levels of immunization with recombinant OspA-glutathione transferase fusion protein on transmission dynamics from infected P. leucopus to larval ticks. Control mice were vaccinated with glutathione transferase alone. All mice were experimentally infected with B. burgdorferi before vaccination. The immune responses of the immunized mice were assessed by enzyme-linked immunosorbent assay for antibodies to OspA. Transmission of B. burgdorferi from infected mice was determined by xenodiagnosis with uninfected larval ticks. Spirochetes in ticks were counted by direct immunofluorescence assay. The concentration of antibody to OspA increased with each OspA vaccination but most markedly after the first and second vaccinations. In comparison with control mice, there was reduced transmission by OspA-vaccinated mice to uninfected ticks. One, two, or three doses of OspA reduced infection prevalence in xenodiagnostic ticks by 48%, 92%, or 99% and the numbers of spirochetes per tick by 84%, 98%, or 99%, respectively. This study suggests that vaccination of P. leucopus with OspA could reduce transmission to the tick vector in nature despite prior infection of the reservoir host.

  12. Temporal Changes in Outer Surface Proteins A and C of the Lyme Disease-Associated Spirochete, Borrelia burgdorferi, during the Chain of Infection in Ticks and Mice

    PubMed Central

    Schwan, Tom G.; Piesman, Joseph

    2000-01-01

    The Lyme disease-associated spirochete, Borrelia burgdorferi, is maintained in enzootic cycles involving Ixodes ticks and small mammals. Previous studies demonstrated that B. burgdorferi expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed ticks. However, after ticks feed on blood, some spirochetes stop making OspA and express OspC. Our current work examined the timing and frequency of OspA and OspC expression by B. burgdorferi in infected Ixodes scapularis nymphs as they fed on uninfected mice and in uninfected I. scapularis larvae and nymphs as they first acquired spirochetes from infected mice. Smears of midguts from previously infected ticks were prepared at 12- or 24-h intervals following attachment through repletion at 96 h, and spirochetes were stained for immunofluorescence for detection of antibodies to OspA and OspC. As shown previously, prior to feeding spirochetes in nymphs expressed OspA but not OspC. During nymphal feeding, however, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became detectable. In fact, spirochetes rapidly began to express OspC, with the greatest proportion of spirochetes having this protein at 48 h of attachment and then with the proportion decreasing significantly by the time that the ticks had completed feeding. In vitro cultivation of the spirochete at different temperatures showed OspC to be most abundant when the spirochetes were grown at 37°C. Yet, the synthesis of this protein waned with continuous passage at this temperature. Immunofluorescence staining of spirochetes in smears of midguts from larvae and nymphs still attached or having completed feeding on infected mice demonstrated that OspA but not OspC was produced by these spirochetes recently acquired from mice. Therefore, the temporal synthesis of OspC by spirochetes only in feeding ticks that were infected prior to the blood meal suggests that this surface protein is involved in

  13. Purine Salvage Pathways among Borrelia Species▿

    PubMed Central

    Pettersson, Jonas; Schrumpf, Merry E.; Raffel, Sandra J.; Porcella, Stephen F.; Guyard, Cyril; Lawrence, Kevin; Gherardini, Frank C.; Schwan, Tom G.

    2007-01-01

    Genome sequencing projects on two relapsing fever spirochetes, Borrelia hermsii and Borrelia turicatae, revealed differences in genes involved in purine metabolism and salvage compared to those in the Lyme disease spirochete Borrelia burgdorferi. The relapsing fever spirochetes contained six open reading frames that are absent from the B. burgdorferi genome. These genes included those for hypoxanthine-guanine phosphoribosyltransferase (hpt), adenylosuccinate synthase (purA), adenylosuccinate lyase (purB), auxiliary protein (nrdI), the ribonucleotide-diphosphate reductase alpha subunit (nrdE), and the ribonucleotide-diphosphate reductase beta subunit (nrdF). Southern blot assays with multiple Borrelia species and isolates confirmed the presence of these genes in the relapsing fever group of spirochetes but not in B. burgdorferi and related species. TaqMan real-time reverse transcription-PCR demonstrated that the chromosomal genes (hpt, purA, and purB) were transcribed in vitro and in mice. Phosphoribosyltransferase assays revealed that, in general, B. hermsii exhibited significantly higher activity than did the B. burgdorferi cell lysate, and enzymatic activity was observed with adenine, hypoxanthine, and guanine as substrates. B. burgdorferi showed low but detectable phosphoribosyltransferase activity with hypoxanthine even though the genome lacks a discernible ortholog to the hpt gene in the relapsing fever spirochetes. B. hermsii incorporated radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did B. burgdorferi. This complete pathway for purine salvage in the relapsing fever spirochetes may contribute, in part, to these spirochetes achieving high cell densities in blood. PMID:17502392

  14. Geographic uniformity of the Lyme disease spirochete (Borrelia burgdorferi) and its shared history with tick vector (Ixodes scapularis) in the Northeastern United States.

    PubMed

    Qiu, Wei-Gang; Dykhuizen, Daniel E; Acosta, Michael S; Luft, Benjamin J

    2002-03-01

    Over 80% of reported cases of Lyme disease in the United States occur in coastal regions of northeastern and mid-Atlantic states. The genetic structure of the Lyme disease spirochete (Borrelia burgdorferi) and its main tick vector (Ixodes scapularis) was studied concurrently and comparatively by sampling natural populations of I. scapularis ticks along the East Coast from 1996 to 1998. Borrelia is genetically highly diverse at the outer surface protein ospC. Since Borrelia is highly clonal, the ospC alleles can be used to define clones. A newly designed reverse line blotting (RLB) assay shows that up to 10 Borrelia clones can infect a single tick. The clone frequencies in Borrelia populations are the same across the Northeast. On the other hand, I. scapularis populations show strong regional divergence (among northeastern, mid-Atlantic, and southern states) as well as local differentiation. The high genetic diversity within Borrelia populations and the disparity in the genetic structure between Borrelia and its tick vector are likely consequences of strong balancing selection on local Borrelia clones. Demographically, both Borrelia and I. scapularis populations in the Northeast show the characteristics of a species that has recently expanded from a population bottleneck. Major geological and ecological events, such as the last glacial maximum (18,000 years ago) and the modern-day expansion of tick habitats, are likely causes of the observed "founder effects" for the two organisms in the Northeast. We therefore conclude that the genetic structure of B. burgdorferi has been intimately shaped by the natural history of its main vector, the northern lineage of I. scapularis ticks. PMID:11901105

  15. Plaques of Alzheimer's disease originate from cysts of Borrelia burgdorferi, the Lyme disease spirochete.

    PubMed

    MacDonald, Alan B

    2006-01-01

    Here is hypothesized a truly revolutionary notion that rounded cystic forms of Borrelia burgdorferi are the root cause of the rounded structures called plaques in the Alzheimer brain. Rounded "plaques' in high density in brain tissue are emblematic of Alzheimer's disease (AD). Plaques may be conceptualized as rounded "pock mark-like" areas of brain tissue injury. In this century, in brain tissue of AD, plaques are Amyloid Plaques according to the most up to date textbooks. In the last century, however, Dr. Alois Alzheimer did not require amyloid as the pathogenesis for either the disease or for the origin of its plaques. Surely, amyloid is an event in AD, but it may not be the primal cause of AD. Indeed in plaques, amyloid is regularly represented by the "congophilic core" structure which is so named because the waxy amyloid material binds the congo red stain and is congophilic. However an accepted subset of plaques in AD is devoid of a congophilic amyloid core region (these plaques "cotton wool" type plaques, lack a central congophilic core structure). Furthermore, there is "plaque diversity" in Alzheimer's; small, medium and large plaques parallel variable cystic diameters for Borrelia burgdorferi. Perturbations of AD plaque structure (i.e. young plaques devoid of a central core and older plaques with or without a central core structure) offer room for an alternate pathway for explanation of ontogeny of the plaque structures. If amyloid is not required to initiate all of the possible plaques in Alzheimer's, is it possible that amyloid just a by product of a more fundamental primal path to dementia? If a byproduct status is assigned to amyloid in the realm of plaque formation, then is amyloid also an epiphenomenon rather than a primary pathogenesis for Alzheimer's disease. In the "anatomy is destiny" model, cysts of borrelia are always round. Why then not accept roundness as a fundamental "structure determines function" argument for the answer to the mystery of

  16. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    SciTech Connect

    Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

    2012-03-14

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

  17. A phylogenomic and molecular marker based proposal for the division of the genus Borrelia into two genera: the emended genus Borrelia containing only the members of the relapsing fever Borrelia, and the genus Borreliella gen. nov. containing the members of the Lyme disease Borrelia (Borrelia burgdorferi sensu lato complex).

    PubMed

    Adeolu, Mobolaji; Gupta, Radhey S

    2014-06-01

    The genus Borrelia contains two groups of organisms: the causative agents of Lyme disease and their relatives and the causative agents of relapsing fever and their relatives. These two groups are morphologically indistinguishable and are difficult to distinguish biochemically. In this work, we have carried out detailed comparative genomic analyses on protein sequences from 38 Borrelia genomes to identify molecular markers in the forms of conserved signature inserts/deletions (CSIs) that are specifically found in the Borrelia homologues, and conserved signature proteins (CSPs) which are uniquely present in Borrelia species. Our analyses have identified 31 CSIs and 82 CSPs that are uniquely shared by all sequenced Borrelia species, providing molecular markers for this group of organisms. In addition, our work has identified 7 CSIs and 21 CSPs which are uniquely found in the Lyme disease Borrelia species and eight CSIs and four CSPs that are specific for members of the relapsing fever Borrelia group. Additionally, 38 other CSIs, in proteins which are uniquely found in Borrelia species, also distinguish these two groups of Borrelia. The identified CSIs and CSPs provide novel and highly specific molecular markers for identification and distinguishing between the Lyme disease Borrelia and the relapsing fever Borrelia species. We also report the results of average nucleotide identity (ANI) analysis on Borrelia genomes and phylogenetic analysis for these species based upon 16S rRNA sequences and concatenated sequences for 25 conserved proteins. These analyses also support the distinctness of the two Borrelia clades. On the basis of the identified molecular markers, the results from ANI and phylogenetic studies, and the distinct pathogenicity profiles and arthropod vectors used by different Borrelia spp. for their transmission, we are proposing a division of the genus Borrelia into two separate genera: an emended genus Borrelia, containing the causative agents of relapsing

  18. Prevalence of the Lyme Disease Spirochete, Borrelia burgdorferi, in Blacklegged Ticks, Ixodes scapularis at Hamilton-Wentworth, Ontario

    PubMed Central

    Scott, John D.; Anderson, John F.; Durden, Lance A.; Smith, Morgan L.; Manord, Jodi M.; Clark, Kerry L.

    2016-01-01

    Lyme disease has emerged as a major health concern in Canada, where the etiological agent, Borrelia burgdorferi sensu lato (s.l.), a spirochetal bacterium, is typically spread by the bite of certain ticks. This study explores the presence of B. burgdorferi s.l. in blacklegged ticks, Ixodes scapularis, collected at Dundas, Ontario (a locality within the region of Hamilton-Wentworth). Using passive surveillance, veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and cats with no history of travel. Additionally, I. scapularis specimens were submitted from local residents and collected by flagging. Overall, 12 (41%) of 29 blacklegged ticks were infected with B. burgdorferi s.l. Using polymerase chain reaction (PCR) and DNA sequencing, two borrelial amplicons were characterized as B. burgdorferi sensu stricto (s.s.), a genospecies pathogenic to humans and certain domestic animals. Notably, three different vertebrate hosts each had two engorged I. scapularis females removed on the same day and, likewise, one cat had three repeat occurrences of this tick species. These multiple infestations suggest that a population of I. scapularis may be established in this area. The local public health unit has been underreporting the presence of B. burgdorferi s.l.-infected I. scapularis in the area encompassing Dundas. Our findings raise concerns about the need to erect tick warning signs in parkland areas. Veterinarians, medical professionals, public health officials, and the general public must be vigilant that Lyme disease-carrying blacklegged ticks pose a public health risk in the Dundas area and the surrounding Hamilton-Wentworth region. PMID:27226771

  19. Whole-Genome Sequences of Borrelia bissettii Borrelia valaisiana and Borrelia spielmanii

    SciTech Connect

    Schutzer S. E.; Dunn J.; Fraser-Liggett C. M.; Qiu W.-G.; Kraiczy P.; Mongodin E. F.; Luft B. J.; Casjens S. R.

    2012-01-01

    It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127.

  20. Spirochetes in the spleen of a patient with chronic Lyme disease.

    PubMed

    Cimmino, M A; Azzolini, A; Tobia, F; Pesce, C M

    1989-01-01

    A 54-year-old man had intermittent evening fever, arthralgia, transient erythematous macular eruption on the skin, and splenomegaly of two year's duration. Immunofluorescence tests for Borrelia burgdorferi serum antibodies had positive results, but G-penicillin treatment was ineffective. Splenectomy with lymph node biopsy was performed to rule out lymphoproliferative disorders. Borrelia-like spirochetes were identified histologically in the spleen; this finding was consistent with persistence of B. burgdorferi organisms in inner organs in chronic Lyme disease.

  1. A comparative study of mammalian and reptilian alternative pathway of complement-mediated killing of the Lyme disease spirochete (Borrelia burgdorferi).

    PubMed

    Kuo, M M; Lane, R S; Giclas, P C

    2000-12-01

    The potential bactericidal activity of the alternative complement pathway of mammalian and reptilian sera to Borrelia burgdorferi sensu stricto (s.s.) was evaluated in vitro. Complement-mediated killing was observed when cultured spirochetes were inoculated into sera from the western fence lizard (Sceloporus occidentalis) and from the southern alligator lizard (Elgaria multicarinata), but not when they were inoculated into serum from either the deer mouse (Peromyscus maniculatus) or from humans. Spirochetes were still alive after 4 hr in lizard serum that had been preheated at 56 C for 30 min to inactivate complement. Furthermore, when lizard serum was chelated with 10 mM ethylenediaminetetraacetic acid to block all complement activation, borreliacidal activity was arrested. When lizard serum was chelated with 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid plus 4 mM MgCl2 to block only classical complement pathway activation, >85% of spirochetes were immobilized within 1 hr. Differences in B. burgdorferi s.s. mortality were not observed when chelators with or without MgCl2 were added to serum from either deer mice or humans. Proteins comprising the alternative complement pathway are responsible for the borreliacidal activity observed in the blood of S. occidentalis and E. multicarinata. PMID:11191895

  2. Borrelia miyamotoi–Associated Neuroborreliosis in Immunocompromised Person

    PubMed Central

    Lobenstein, Sabine; Hermann, Beate; Margos, Gabriele; Fingerle, Volker

    2016-01-01

    Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi–induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods. PMID:27533748

  3. Borrelia miyamotoi-Associated Neuroborreliosis in Immunocompromised Person.

    PubMed

    Boden, Katharina; Lobenstein, Sabine; Hermann, Beate; Margos, Gabriele; Fingerle, Volker

    2016-09-01

    Borrelia miyamotoi is a newly recognized human pathogen in the relapsing fever group of spirochetes. We investigated a case of B. miyamotoi infection of the central nervous system resembling B. burgdorferi-induced Lyme neuroborreliosis and determined that this emergent agent of central nervous system infection can be diagnosed with existing methods. PMID:27533748

  4. Occurrence of Borrelia burgdorferi Sensu Lato in Ixodes ricinus Ticks with First Identification of Borrelia miyamotoi in Vojvodina, Serbia.

    PubMed

    Potkonjak, Aleksandar; Kleinerman, Gabriela; Gutiérrez, Ricardo; Savić, Sara; Vračar, Vuk; Nachum-Biala, Yaarit; Jurišić, Aleksandar; Rojas, Alicia; Petrović, Aleksandra; Ivanović, Ivana; Harrus, Shimon; Baneth, Gad

    2016-10-01

    Lyme borreliosis is the most common tick-borne infectious disease in Eurasia. Borrelia miyamotoi is the only known relapsing fever Borrelia group spirochete transmitted by Ixodes species. The aim of this study was to investigate the presence of Lyme Borrelia spp. and relapsing fever Borrelia spp. in Ixodes ricinus ticks collected from dogs and the vegetation from different parts of Vojvodina, Serbia. A total of 71 Ixodes ricinus ticks were collected and screened for the presence of Lyme Borrelia spp. group and relapsing fever Borrelia spp. by real-time PCR for the Borrelia flagellin B (flaB) gene followed by DNA sequencing of PCR products. Species identification was verified by PCR of the outer surface protein A (ospA) gene for Lyme Disease Borrelia spp. and by PCR of the glycerophosphodiester phosphodiesterase (glpQ) gene for relapsing fever Borrelia spp. Lyme Borrelia spp. were found in 15/71 (21.13%) of the ticks evaluated and included B. luisitaniae (11.3%), B. afzelii (7%), B. valaisiana (1.4%), and B. garinii (1.4%). Borrelia miyamotoi, from the relapsing fever Borrelia complex, was found, for the first time in Serbia, in one (1.4%) nymph collected from the environment. Co-infections between Borrelia species in ticks were not detected. These results suggest that the dominance of species within B. burgdorferi s.l. complex in I. ricinus ticks may vary over time and in different geographic regions. Further systematic studies of Borrelia species in vectors and reservoir hosts are needed to understand eco-epidemiology of these zoonotic infections and how to prevent human infection in the best way.

  5. Occurrence of Borrelia burgdorferi Sensu Lato in Ixodes ricinus Ticks with First Identification of Borrelia miyamotoi in Vojvodina, Serbia.

    PubMed

    Potkonjak, Aleksandar; Kleinerman, Gabriela; Gutiérrez, Ricardo; Savić, Sara; Vračar, Vuk; Nachum-Biala, Yaarit; Jurišić, Aleksandar; Rojas, Alicia; Petrović, Aleksandra; Ivanović, Ivana; Harrus, Shimon; Baneth, Gad

    2016-10-01

    Lyme borreliosis is the most common tick-borne infectious disease in Eurasia. Borrelia miyamotoi is the only known relapsing fever Borrelia group spirochete transmitted by Ixodes species. The aim of this study was to investigate the presence of Lyme Borrelia spp. and relapsing fever Borrelia spp. in Ixodes ricinus ticks collected from dogs and the vegetation from different parts of Vojvodina, Serbia. A total of 71 Ixodes ricinus ticks were collected and screened for the presence of Lyme Borrelia spp. group and relapsing fever Borrelia spp. by real-time PCR for the Borrelia flagellin B (flaB) gene followed by DNA sequencing of PCR products. Species identification was verified by PCR of the outer surface protein A (ospA) gene for Lyme Disease Borrelia spp. and by PCR of the glycerophosphodiester phosphodiesterase (glpQ) gene for relapsing fever Borrelia spp. Lyme Borrelia spp. were found in 15/71 (21.13%) of the ticks evaluated and included B. luisitaniae (11.3%), B. afzelii (7%), B. valaisiana (1.4%), and B. garinii (1.4%). Borrelia miyamotoi, from the relapsing fever Borrelia complex, was found, for the first time in Serbia, in one (1.4%) nymph collected from the environment. Co-infections between Borrelia species in ticks were not detected. These results suggest that the dominance of species within B. burgdorferi s.l. complex in I. ricinus ticks may vary over time and in different geographic regions. Further systematic studies of Borrelia species in vectors and reservoir hosts are needed to understand eco-epidemiology of these zoonotic infections and how to prevent human infection in the best way. PMID:27574731

  6. Population structure of the lyme borreliosis spirochete Borrelia burgdorferi in the western black-legged tick (Ixodes pacificus) in Northern California.

    PubMed

    Girard, Yvette A; Travinsky, Bridgit; Schotthoefer, Anna; Fedorova, Natalia; Eisen, Rebecca J; Eisen, Lars; Barbour, Alan G; Lane, Robert S

    2009-11-01

    Factors potentially contributing to the lower incidence of Lyme borreliosis (LB) in the far-western than in the northeastern United States include tick host-seeking behavior resulting in fewer human tick encounters, lower densities of Borrelia burgdorferi-infected vector ticks in peridomestic environments, and genetic variation among B. burgdorferi spirochetes to which humans are exposed. We determined the population structure of B. burgdorferi in over 200 infected nymphs of the primary bridging vector to humans, Ixodes pacificus, collected in Mendocino County, CA. This was accomplished by sequence typing the spirochete lipoprotein ospC and the 16S-23S rRNA intergenic spacer (IGS). Thirteen ospC alleles belonging to 12 genotypes were found in California, and the two most abundant, ospC genotypes H3 and E3, have not been detected in ticks in the Northeast. The most prevalent ospC and IGS biallelic profile in the population, found in about 22% of ticks, was a new B. burgdorferi strain defined by ospC genotype H3. Eight of the most common ospC genotypes in the northeastern United States, including genotypes I and K that are associated with disseminated human infections, were absent in Mendocino County nymphs. ospC H3 was associated with hardwood-dominated habitats where western gray squirrels, the reservoir host, are commonly infected with LB spirochetes. The differences in B. burgdorferi population structure in California ticks compared to the Northeast emphasize the need for a greater understanding of the genetic diversity of spirochetes infecting California LB patients. PMID:19783741

  7. Interaction of the Lyme Disease Spirochete Borrelia burgdorferi with Brain Parenchyma Elicits Inflammatory Mediators from Glial Cells as Well as Glial and Neuronal Apoptosis

    PubMed Central

    Ramesh, Geeta; Borda, Juan T.; Dufour, Jason; Kaushal, Deepak; Ramamoorthy, Ramesh; Lackner, Andrew A.; Philipp, Mario T.

    2008-01-01

    Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often manifests by causing neurocognitive deficits. As a possible mechanism for Lyme neuroborreliosis, we hypothesized that B. burgdorferi induces the production of inflammatory mediators in the central nervous system with concomitant neuronal and/or glial apoptosis. To test our hypothesis, we constructed an ex vivo model that consisted of freshly collected slices from brain cortex of a rhesus macaque and allowed live B. burgdorferi to penetrate the tissue. Numerous transcripts of genes that regulate inflammation as well as oligodendrocyte and neuronal apoptosis were significantly altered as assessed by DNA microarray analysis. Transcription level increases of 7.43-fold (P = 0.005) for the cytokine tumor necrosis factor-α and 2.31-fold (P = 0.016) for the chemokine interleukin (IL)-8 were also detected by real-time-polymerase chain reaction array analysis. The immune mediators IL-6, IL-8, IL-1β, COX-2, and CXCL13 were visualized in glial cells in situ by immunofluorescence staining and confocal microscopy. Concomitantly, significant proportions of both oligodendrocytes and neurons undergoing apoptosis were present in spirochete-stimulated tissues. IL-6 production by astrocytes in addition to oligodendrocyte apoptosis were also detected, albeit at lower levels, in rhesus macaques that had received in vivo intraparenchymal stereotaxic inoculations of live B. burgdorferi. These results provide proof of concept for our hypothesis that B. burgdorferi produces inflammatory mediators in the central nervous system, accompanied by glial and neuronal apoptosis. PMID:18832582

  8. Interaction of the Lyme disease spirochete Borrelia burgdorferi with brain parenchyma elicits inflammatory mediators from glial cells as well as glial and neuronal apoptosis.

    PubMed

    Ramesh, Geeta; Borda, Juan T; Dufour, Jason; Kaushal, Deepak; Ramamoorthy, Ramesh; Lackner, Andrew A; Philipp, Mario T

    2008-11-01

    Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often manifests by causing neurocognitive deficits. As a possible mechanism for Lyme neuroborreliosis, we hypothesized that B. burgdorferi induces the production of inflammatory mediators in the central nervous system with concomitant neuronal and/or glial apoptosis. To test our hypothesis, we constructed an ex vivo model that consisted of freshly collected slices from brain cortex of a rhesus macaque and allowed live B. burgdorferi to penetrate the tissue. Numerous transcripts of genes that regulate inflammation as well as oligodendrocyte and neuronal apoptosis were significantly altered as assessed by DNA microarray analysis. Transcription level increases of 7.43-fold (P = 0.005) for the cytokine tumor necrosis factor-alpha and 2.31-fold (P = 0.016) for the chemokine interleukin (IL)-8 were also detected by real-time-polymerase chain reaction array analysis. The immune mediators IL-6, IL-8, IL-1beta, COX-2, and CXCL13 were visualized in glial cells in situ by immunofluorescence staining and confocal microscopy. Concomitantly, significant proportions of both oligodendrocytes and neurons undergoing apoptosis were present in spirochete-stimulated tissues. IL-6 production by astrocytes in addition to oligodendrocyte apoptosis were also detected, albeit at lower levels, in rhesus macaques that had received in vivo intraparenchymal stereotaxic inoculations of live B. burgdorferi. These results provide proof of concept for our hypothesis that B. burgdorferi produces inflammatory mediators in the central nervous system, accompanied by glial and neuronal apoptosis. PMID:18832582

  9. Borrelia miyamotoi Disease: Neither Lyme Disease Nor Relapsing Fever.

    PubMed

    Telford, Sam R; Goethert, Heidi K; Molloy, Philip J; Berardi, Victor P; Chowdri, Hanumara Ram; Gugliotta, Joseph L; Lepore, Timothy J

    2015-12-01

    Borrelia miyamotoi disease (BMD) is a newly recognized borreliosis globally transmitted by ticks of the Ixodes persulcatus species complex. Once considered to be a tick symbiont with no public health implications, B miyamotoi is increasingly recognized as the agent of a nonspecific febrile illness often misdiagnosed as acute Lyme disease without rash, or as ehrlichiosis. The frequency of its diagnosis in the northeastern United States is similar to that of human granulocytic ehrlichiosis. A diagnosis of BMD is confirmed by polymerase chain reaction analysis of acute blood samples, or by seroconversion using a recombinant glycerophosphodiester phosphodiesterase enzyme immunoassay. BMD is successfully treated with oral doxycycline or amoxicillin. PMID:26593262

  10. Borrelia miyamotoi Disease: Neither Lyme Disease Nor Relapsing Fever.

    PubMed

    Telford, Sam R; Goethert, Heidi K; Molloy, Philip J; Berardi, Victor P; Chowdri, Hanumara Ram; Gugliotta, Joseph L; Lepore, Timothy J

    2015-12-01

    Borrelia miyamotoi disease (BMD) is a newly recognized borreliosis globally transmitted by ticks of the Ixodes persulcatus species complex. Once considered to be a tick symbiont with no public health implications, B miyamotoi is increasingly recognized as the agent of a nonspecific febrile illness often misdiagnosed as acute Lyme disease without rash, or as ehrlichiosis. The frequency of its diagnosis in the northeastern United States is similar to that of human granulocytic ehrlichiosis. A diagnosis of BMD is confirmed by polymerase chain reaction analysis of acute blood samples, or by seroconversion using a recombinant glycerophosphodiester phosphodiesterase enzyme immunoassay. BMD is successfully treated with oral doxycycline or amoxicillin.

  11. Diversity and Distribution of Borrelia hermsii

    PubMed Central

    Raffel, Sandra J.; Schrumpf, Merry E.; Porcella, Stephen F.

    2007-01-01

    Borrelia hermsii is the most common cause of tickborne relapsing fever in North America. DNA sequences of the 16S–23S rDNA noncoding intergenic spacer (IGS) region were determined for 37 isolates of this spirochete. These sequences distinguished the 2 genomic groups of B. hermsii identified previously with other loci. Multiple IGS genotypes were identified among isolates from an island, which suggested that birds might play a role in dispersing these spirochetes in nature. In support of this theory, all stages of the tick vector Ornithodoros hermsi fed successfully on birds in the laboratory and advanced in their life cycle. B. hermsii produced a detectable spirochetemia in 1 chicken inoculated subcutaneously. Additional work is warranted to explore the role of birds as enzootic hosts for this relapsing fever spirochete. PMID:17552097

  12. Expression of the Tick-Associated Vtp Protein of Borrelia hermsii in a Murine Model of Relapsing Fever

    PubMed Central

    Marcsisin, Renee A.; Lewis, Eric R. G.; Barbour, Alan G.

    2016-01-01

    Borrelia hermsii, a spirochete and cause of relapsing fever, is notable for its immune evasion by multiphasic antigenic variation within its vertebrate host. This is based on a diverse repertoire of surface antigen genes, only one of which is expressed at a time. Another major surface protein, the Variable Tick Protein (Vtp), is expressed in the tick vector and is invariable at its genetic locus. Given the limited immune systems of ticks, the finding of considerable diversity among the Vtp proteins of different strains of B. hermsii was unexpected. We investigated one explanation for this diversity of Vtp proteins, namely expression of the protein in mammals and a consequent elicitation of a specific immune response. Mice were infected with B. hermsii of either the HS1 or CC1 strain, which have antigenically distinctive Vtp proteins but otherwise have similar repertoires of the variable surface antigens. Subsequently collected sera were examined for antibody reactivities against Vtp and other antigens using Western blot analysis, dot blot, and protein microarray. Week-6 sera of infected mice contained antibodies that were largely specific for the Vtp of the infecting strain and were not attributable to antibody cross-reactivities. The antibody responses of the mice infected with different strains were otherwise similar. Further evidence of in vivo expression of the vtp gene was from enumeration of cDNA sequence reads that mapped to a set of selected B. hermsii genes. This measure of transcription of the infecting strain’s vtp gene was ~10% of that for the abundantly-expressed, serotype-defining variable antigen gene but similar to that of genes known for in vivo expression. The findings of Vtp expression in a vertebrate host and elicitation of a specific anti-Vtp antibody response support the view that balancing selection by host adaptive immunity accounts in part for the observed diversity of Vtp proteins. PMID:26918760

  13. Louse-borne relapsing fever in a refugee from Somalia arriving in Belgium.

    PubMed

    Darcis, Gilles; Hayette, Marie-Pierre; Bontems, Sebastien; Sauvage, Anne-Sophie; Meuris, Christelle; Van Esbroeck, Marjan; Leonard, Philippe

    2016-03-01

    We report a case of louse-borne relapsing fever (LBRF) in a refugee from Somalia who had arrived in Belgium a few days earlier. He complained of myalgia and secondarily presented fever. Blood smears revealed spirochetes later identified as Borrelia recurrentis. LBRF should be considered in countries hosting refugees, particularly those who transit through endemic regions. PMID:27356309

  14. Louse-borne relapsing fever in a refugee from Somalia arriving in Belgium.

    PubMed

    Darcis, Gilles; Hayette, Marie-Pierre; Bontems, Sebastien; Sauvage, Anne-Sophie; Meuris, Christelle; Van Esbroeck, Marjan; Leonard, Philippe

    2016-03-01

    We report a case of louse-borne relapsing fever (LBRF) in a refugee from Somalia who had arrived in Belgium a few days earlier. He complained of myalgia and secondarily presented fever. Blood smears revealed spirochetes later identified as Borrelia recurrentis. LBRF should be considered in countries hosting refugees, particularly those who transit through endemic regions.

  15. Fibronectin-Binding Protein of Borrelia hermsii Expressed in the Blood of Mice with Relapsing Fever

    PubMed Central

    Lewis, Eric R. G.; Marcsisin, Renee A.; Campeau Miller, Shelley A.; Hue, Fong; Phillips, April; AuCoin, David P.

    2014-01-01

    To identify and characterize surface proteins expressed by the relapsing fever (RF) agent Borrelia hermsii in the blood of infected mice, we used a cell-free filtrate of their blood to immunize congenic naive mice. The resultant antiserum was used for Western blotting of cell lysates, and gel slices corresponding to reactive bands were subjected to liquid chromatography-tandem mass spectrometry, followed by a search of the proteome database with the peptides. One of the immunogens was identified as the BHA007 protein, which is encoded by a 174-kb linear plasmid. BHA007 had sequence features of lipoproteins, was surface exposed by the criteria of in situ protease susceptibility and agglutination of Vtp− cells by anti-BHA007 antibodies, and was not essential for in vitro growth. BHA007 elicited antibodies during experimental infection of mice, but immunization with recombinant protein did not confer protection against needle-delivered infection. Open reading frames (ORFs) orthologous to BHA007 were found on large plasmids of other RF species, including the coding sequences for the CihC proteins of Borrelia duttonii and B. recurrentis, but not in Lyme disease Borrelia species. Recombinant BHA007 bound both human and bovine fibronectin with Kd (dissociation constant) values of 22 and 33 nM, respectively, and bound to C4-binding protein with less affinity. The distant homology of BHA007 and its orthologs to BBK32 proteins of Lyme disease species, as well as to previously described BBK32-like proteins in relapsing fever species, indicates that BHA007 is a member of a large family of multifunctional proteins in Borrelia species that bind to fibronectin as well as other host proteins. PMID:24686059

  16. [Ticks Ixodes ricinus (Linnaeus, 1758) from selected municipal forests of the city Poznań and their infection with the spirochetes Borrelia burgdorferi senso lato].

    PubMed

    Nowosad, A; Jenek, J; Głazaczow, A; Wal, M

    1999-01-01

    The results of research (1997-1998) on the occurrence of the spirochetes Borrelia burgdorferi s.l. in ticks Ixodes ricinus (L.) in selected municipal forests of the city of Poznań (localities--districts of Poznań: 1 Debiec, 2 Marcelin, 3 Golecin and Wola, 4 Krzyzowniki and Smochowice, 5 Kiekrz and Strzeszynek, 6 Morasko, 7 Piatkowo, 8 Umultowo, 9 Naramowice and Rózany Młyn, 10 Malta and Antoninek) are presented. A total of 1432 ticks were collected from 10 localities (748 larvae, 590 nymphs, 47 males, and 47 females). Out of this number, 266 specimens were selected at random for further analysis (20 larvae, 160 nymphs, 44 males, and 42 females) which were then tested for the presence of the spirochetes using the PCR technique (tab. I-III, fig. 1). Spirochetes were found in 60 specimens (22.6%). Percentages of infected nymphs and males were similar: 25.6% and 27.3%, respectively. The level of infection of females was lower (14.3%) and of larvae lowest (5.0%). Infected ticks were found in all ten localities, but their proportions differed from site to site and varied from 9.5% (Piatkowo) to 34.6% (Krzyzowniki and Smochowice). Special attention was devoted to those municipal woods where ticks were abundant (Kiekrz and Strzeszynek, as well as Malta and Antoninek, and relatively numerous Debiec) and where their extensiveness of infestation was high (Krzyzowniki and Smochowice: 34.6%; Debiec: 29.6%; Naramowice and Rózany Młyn: 28.6%; Malta and Antoninek: 28.1%; and Golecin and Wola: 26.9%). After summing up all the data from the literature on Wielkopolska and the city of Poznań, the mean extensiveness of infestation in Wielkopolska turns out to be 21.8% and in Poznań slightly higher, 22.2% (tab. IV). The infection levels of the particular developmental stages are different, though: highly variable in nymphs (8.3-25.6%), and more stable in males (22.0-27.3%) and females (22.0-24.5%).

  17. Molecular identification of Borrelia genus in questing hard ticks from Portugal: Phylogenetic characterization of two novel Relapsing Fever-like Borrelia sp.

    PubMed

    Nunes, Mónica; Parreira, Ricardo; Maia, Carla; Lopes, Nádia; Fingerle, Volker; Vieira, M Luísa

    2016-06-01

    In the last decades, several studies have reported pathogenic species of Borrelia related to those that cause Tick-borne Relapsing Fever (RF), but unexpectedly suggesting their transmission by hard ticks, known vectors of Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species, rather than by soft ticks. This study was designed to update the presence of B. burgdorferi s.l. species in ticks from several districts of mainland Portugal, where Ixodes ricinus had been previously described. Ticks (a total of 2915 specimens) were collected in seven districts throughout the country, and analyzed using molecular methods. Three nested-PCR protocols, targeting the flagellin gene (flaB), the intergenic spacer region (IGS) located between 5S and 23S rRNA, and the glpQ gene, and a conventional PCR targeting the 16S rRNA, were used for Borrelia DNA detection. Borrelia DNA was detected in 3% of the ticks from Braga, Vila Real, Lisboa, Setúbal, Évora and Faro districts. The obtained amplicons were sequenced and analyzed by BLASTn, and 15/63 (24%) matched with homologous sequences from Borrelia lusitaniae and 15/63 (24%) with B. garinii, being these the most prevalent species. DNA from B. burgdorferi sensu stricto (s.s.), B. valaisiana and B. afzelii were detected in 7/63 (11%), 6/63 (10%), and 2/63 (3%) of the specimens, respectively. Unexpectedly, DNA sequence (flaB) analysis from eight (13%) samples, two from Rhipicephalus sanguineus and six from Haemaphysalis punctata tick species, revealed high homology with RF-like Borrelia. Phylogenetic analyses obtained from three genetic markers (16S rRNA, flaB, and glpQ) confirmed their congruent inclusion in a strongly supported RF cluster, where they segregated in two subgroups which differ from the other Relapsing Fever species. Therefore, the results confirm the circulation of multiple species of B. burgdorferi s.l. over a wide geographic range, covering most of the Portuguese mainland territory. Surprisingly, the obtained data

  18. Molecular identification of Borrelia genus in questing hard ticks from Portugal: Phylogenetic characterization of two novel Relapsing Fever-like Borrelia sp.

    PubMed

    Nunes, Mónica; Parreira, Ricardo; Maia, Carla; Lopes, Nádia; Fingerle, Volker; Vieira, M Luísa

    2016-06-01

    In the last decades, several studies have reported pathogenic species of Borrelia related to those that cause Tick-borne Relapsing Fever (RF), but unexpectedly suggesting their transmission by hard ticks, known vectors of Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species, rather than by soft ticks. This study was designed to update the presence of B. burgdorferi s.l. species in ticks from several districts of mainland Portugal, where Ixodes ricinus had been previously described. Ticks (a total of 2915 specimens) were collected in seven districts throughout the country, and analyzed using molecular methods. Three nested-PCR protocols, targeting the flagellin gene (flaB), the intergenic spacer region (IGS) located between 5S and 23S rRNA, and the glpQ gene, and a conventional PCR targeting the 16S rRNA, were used for Borrelia DNA detection. Borrelia DNA was detected in 3% of the ticks from Braga, Vila Real, Lisboa, Setúbal, Évora and Faro districts. The obtained amplicons were sequenced and analyzed by BLASTn, and 15/63 (24%) matched with homologous sequences from Borrelia lusitaniae and 15/63 (24%) with B. garinii, being these the most prevalent species. DNA from B. burgdorferi sensu stricto (s.s.), B. valaisiana and B. afzelii were detected in 7/63 (11%), 6/63 (10%), and 2/63 (3%) of the specimens, respectively. Unexpectedly, DNA sequence (flaB) analysis from eight (13%) samples, two from Rhipicephalus sanguineus and six from Haemaphysalis punctata tick species, revealed high homology with RF-like Borrelia. Phylogenetic analyses obtained from three genetic markers (16S rRNA, flaB, and glpQ) confirmed their congruent inclusion in a strongly supported RF cluster, where they segregated in two subgroups which differ from the other Relapsing Fever species. Therefore, the results confirm the circulation of multiple species of B. burgdorferi s.l. over a wide geographic range, covering most of the Portuguese mainland territory. Surprisingly, the obtained data

  19. Borrelia crocidurae in Ornithodoros ticks from northwestern Morocco: a range extension in relation to climatic change?

    PubMed

    Souidi, Yassine; Boudebouch, Najma; Ezikouri, Sayeh; Belghyti, Driss; Trape, Jean-François; Sarih, M'hammed

    2014-12-01

    Tick-borne relapsing fever (TBRF) is caused by Borrelia spirochetes transmitted to humans by Argasid soft ticks of the genus Ornithodoros. We investigated the presence of Ornithodoros ticks in rodent burrows in nine sites of the Gharb region of northwestern Morocco where we recently documented a high incidence of TBRF in humans. We assessed the Borrelia infection rate by nested PCR and sequencing. All sites investigated were colonized by ticks of the Ornithodoros marocanus complex and a high proportion of burrows (38.4%) were found to be infested. Borrelia infections were observed in 6.8% of the ticks tested. Two Borrelia species were identified by sequencing: B. hispanica and B. crocidurae. The discovery in northwestern Morocco of Ornithodoros ticks infected by B. crocidurae represents a 350 km range extension of this Sahelo-Saharan spirochete in North Africa. The spread of B. crocidurae may be related to the increasing aridity of northwestern Morocco in relation to climate change.

  20. Phylogeny of a relapsing fever Borrelia species transmitted by the hard tick Ixodes scapularis

    PubMed Central

    Barbour, Alan G.

    2014-01-01

    The discovery of Borrelia species that were related to the agents of relapsing fever but were transmitted by hard ticks rather than soft ticks challenged previous taxonomies based largely on microbe-host specificities and geographic considerations. One of these newly-identified organisms is the Borrelia miyamotoi sensu lato strain LB-2001 from North America and transmitted by Ixodes scapularis. This or related strains have been identified as the cause of human disease, but comparatively little is known about their biology or genetics. Using recently acquired chromosome sequence of LB-2001 together with database sequences and additional sequences determined here, I carried out comparisons of the several species of Borrelia, including those in the two major clades: the relapsing fever group of species and the Lyme disease group of species. Phylogenetic inference at the species level was based on four data sets: whole chromosomes of ~1 Mb each, and concatenated sequences of 19 ribosomal protein genes, 3 conserved nucleic acid enzymes (rpoC, recC, and dnaE), and 4 contiguous genes for nucleotide salvage on a large plasmid. Analyses using neighbor-joining, maximum likelihood, and Bayesian methods were largely concordant for each of the trees. They showed that LB-2001 and related hard tick-associated organisms, like B. lonestari, are deeply positioned within the RF group of species and that these organisms did not, as some earlier estimations had suggested, constitute a paraphyletic group. The analyses also provided further evidence that major changes in host ranges and life cycles, such as hard to soft ticks or vice versa, may not correlate well with overall sequence differences. The genetic differences between LB-2001 and B. miyamotoi sensu stricto justify provisional use of the “sensu lato” designation for LB-2001. PMID:24813576

  1. Fatal spirochetosis due to a relapsing fever-like Borrelia sp. in a northern spotted owl.

    PubMed

    Thomas, Nancy J; Bunikis, Jonas; Barbour, Alan G; Wolcott, Mark J

    2002-01-01

    Acute septicemic spirochetosis was diagnosed in an adult male northern spotted owl (Strix occidentalis caurina) found dead in Kittitas County, Washington, USA. Gross necropsy findings included marked enlargement of the liver and spleen and serofibrinous deposits on the serous membranes lining the body cavities and the pericardial and perihepatic sacs. Microscopic observations included macrophage infiltration in the liver and spleen with mild thrombosis and multifocal necrosis, as well as hemorrhage and acute inflammation in the choroid plexus of the brain. No viruses or pathogenic bacteria were isolated from brain, liver, or spleen, and no parasites were found in blood smears or impression smears of the liver. Chlamydial culture attempts were unsuccessful and no chlamydial antibodies were detected in serum. In silver-stained microscopic sections and by transmission electron microscopy of liver, numerous long, thin, spiral-shaped bacteria were seen in the liver, spleen, cerebral ventricles, and within blood vessels in many organs. The organism was identified as a member of the Borrelia genus by sequence analysis of the PCR-amplified 16S rRNA gene. The most closely related species is B. hermsii, an agent of relapsing fever in humans in the western United States. This is the first report of a relapsing fever-related Borrelia in a wild bird. PMID:11838214

  2. Fatal spirochetosis due to a relapsing fever-like Borrelia sp. in northern spotted owl

    USGS Publications Warehouse

    Thomas, N.J.; Bunikis, J.; Barbour, A.G.; Wolcott, M.J.

    2002-01-01

    Acute septicemic spirochetosis was diagnosed in an adult male northern spotted owl (Strix occidentalis caurina) found dead in Kittitas County, Washington, USA. Gross necropsy findings included marked enlargement of the liver and spleen and serofibrinous deposits on the serous membranes lining the body cavities and the pericardial and perihepatic sacs. Microscopic observations included macrophage infiltration in the liver and spleen with mild thrombosis and multifocal necrosis, as well as hemorrhage and acute inflammation in the choroid plexus of the brain. No viruses or pathogenic bacteria were isolated from brain, liver, or spleen, and no parasites were found in blood smears or impression smears of the liver. Chlamydial culture attempts were unsuccessful and no chlamydial antibodies were detected in serum. In silver-stained microscopic sections and by transmission electron microscopy of liver, numerous long, thin, spiral-shaped bacteria were seen in the liver, spleen, cerebral ventricles, and within blood vessels in many organs. The organism was identified as a member of the Borrelia genus by sequence analysis of the PCR-amplified 16S rRNA gene. The most closely related species is B. hermsii, an agent of relapsing fever in humans in the western United States. This is the first report of a relapsing fever-related Borrelia in a wild bird.

  3. Tickborne Relapsing Fever, Bitterroot Valley, Montana, USA

    PubMed Central

    Christensen, Joshua; Fischer, Robert J.; McCoy, Brandi N.; Raffel, Sandra J.

    2015-01-01

    In July 2013, a resident of the Bitterroot Valley in western Montana, USA, contracted tickborne relapsing fever caused by an infection with the spirochete Borrelia hermsii. The patient’s travel history and activities before onset of illness indicated a possible exposure on his residential property on the eastern side of the valley. An onsite investigation of the potential exposure site found the vector, Ornithodoros hermsi ticks, and 1 chipmunk infected with spirochetes, which on the basis of multilocus sequence typing were identical to the spirochete isolated from the patient. Field studies in other locations found additional serologic evidence and an infected tick that demonstrated a wider distribution of spirochetes circulating among the small mammal populations. Our study demonstrates that this area of Montana represents a previously unrecognized focus of relapsing fever and poses a risk for persons of acquiring this tickborne disease. PMID:25625502

  4. Wild turkey (Meleagris gallopavo) as a host of ixodid ticks, lice, and Lyme disease spirochetes (Borrelia burgdorferi sensu lato) in California state parks.

    PubMed

    Lane, Robert S; Kucera, Thomas F; Barrett, Reginald H; Mun, Jeomhee; Wu, Chunling; Smith, Vincent S

    2006-10-01

    Rio Grande wild turkeys (Meleagris gallopavo intermedia) were evaluated as potential hosts of ixodid ticks, lice, and Lyme disease spirochetes (Borrelia burgdorferi sensu lato [s.l.]) in three state parks in Sonoma County, California, USA, during 2003 and 2004. In total, 113 birds were collected, 50 (44.2%) of which were found to be infested by 361 ixodid ticks representing three species: the western black-legged tick (Ixodes pacificus, n=248), the rabbit tick (Haemaphysalis leporispalustris, n=112), and one American dog tick (Dermacentor variabilis). Year-round the prevalence of all ticks combined was unrelated to the age or sex of turkeys, and the prevalence of infestation by I. pacificus (35.4%) was significantly higher than it was for either H. leporispalustris (14.2%) or D. variabilis (0.9%). The proportion of the two prevalent tick species differed significantly by life stage with 86.3% of the I. pacificus and 82.1% of the H. leporispalustris enumerated being nymphs and larvae, respectively. Three species of lice were collected, including the chicken body louse Menacanthus stramineus (12.5% of total), Chelopistes meleagridis (37.5% of total), and Oxylipeurus polytrapezius (50% of total). The records for all three ticks are the first ever from wild turkeys, and those for the lice are the first from this host in the far-western United States. Wild turkeys potentially were exposed to the feeding activities of I. pacificus nymphs infected with B. burgdorferi s.l. as 15% of host-seeking nymphs (n=200) collected in woodlands used by turkeys as roosting or foraging areas were infected mainly with B. burgdorferi sensu stricto (s.s.). However, only one (1%) of 90 turkey blood specimens tested by PCR contained B. burgdorferi s.s., and four in vitro, complement-protein assays demonstrated that domestic turkey serum is moderately bacteriolytic for this spirochete. Taken together, these findings indicate that wild turkeys are important avian hosts of I. pacificus nymphs

  5. Borrelia burgdorferi enzyme-linked immunosorbent assay for discrimination of OspA vaccination from spirochete infection.

    PubMed Central

    Zhang, Y Q; Mathiesen, D; Kolbert, C P; Anderson, J; Schoen, R T; Fikrig, E; Persing, D H

    1997-01-01

    Recombinant Lyme disease vaccines based on purified preparations of outer surface protein A (OspA) have been shown to be effective in preventing transmission of Borrelia burgdorferi in experimental animal models and are now being tested in humans. Since the most widely used screening tests for Lyme disease are based on a whole-cell sonicate of B. burgdorferi, serologic false positivity in vaccinated persons could result from reactivity to OspA within the antigen preparation. In order to avoid serologic false positivity in vaccinated subjects, we developed an immunoassay based on a low-passage-number, naturally occurring variant of B. burgdorferi which lacks the plasmid encoding OspA and OspB. The use of an antigen preparation derived from this organism provided sensitive and specific detection of B. burgdorferi seropositivity in experimental animals and in human Lyme disease cases. The OspA-B-negative enzyme-linked immunosorbent assay (ELISA) also appeared to be capable of discriminating the vaccinated state from vaccine failure and natural infection in experimental animals. Sera from human subjects participating in a vaccine trial gave false-positive results with an ELISA based on an OspA-containing strain, but no such reactivity was observed when the OspA-negative ELISA was used. We conclude that low-passage-number OspA-B-negative isolates in immunoassays may become useful for the immunologic discrimination of the vaccinated state, natural infection, and vaccine failure. PMID:8968914

  6. Laboratory Diagnosis of Tick-Borne African Relapsing Fevers: Latest Developments

    PubMed Central

    Fotso Fotso, Aurélien; Drancourt, Michel

    2015-01-01

    In Africa, relapsing fevers caused by ectoparasite-borne Borrelia species are transmitted by ticks, with the exception of Borrelia recurrentis, which is a louse-borne spirochete. These tropical diseases are responsible for mild to deadly spirochetemia. Cultured Borrelia crocidurae, Borrelia duttonii, and Borrelia hispanica circulate alongside at least six species that have not yet been cultured in vectors. Direct diagnosis is hindered by the use of non-specific laboratory tools. Indeed, microscopic observation of Borrelia spirochaeta in smears of peripheral blood taken from febrile patients lacks sensitivity and specificity. Although best visualized using dark-field microscopy, the organisms can also be detected using Wright–Giemsa or acridine orange stains. PCR-based detection of specific sequences in total DNA extracted from a specimen can be used to discriminate different relapsing fever Borreliae. In our laboratory, we developed a multiplex real-time PCR assay for the specific detection of B. duttonii/recurrentis and B. crocidurae: multispacer sequence typing accurately identified cultured relapsing fever borreliae and revealed diversity among them. Other molecular typing techniques, such as multilocus sequence analysis of tick-borne relapsing fever borreliae, showed the potential risk of human infection in Africa. Recent efforts to culture and sequence relapsing fever borreliae have provided new information for reassessment of the diversity of these bacteria. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been reported as a means of identifying cultured borreliae and of identifying both vectors and vectorized pathogens such as detecting relapsing fever borreliae directly in ticks. The lack of a rapid diagnosis test restricts the management of such diseases. We produced monoclonal antibodies against B. crocidurae in order to develop cheap assays for the rapid detection of relapsing fever borreliae. In this paper, we

  7. Laboratory Diagnosis of Tick-Borne African Relapsing Fevers: Latest Developments.

    PubMed

    Fotso Fotso, Aurélien; Drancourt, Michel

    2015-01-01

    In Africa, relapsing fevers caused by ectoparasite-borne Borrelia species are transmitted by ticks, with the exception of Borrelia recurrentis, which is a louse-borne spirochete. These tropical diseases are responsible for mild to deadly spirochetemia. Cultured Borrelia crocidurae, Borrelia duttonii, and Borrelia hispanica circulate alongside at least six species that have not yet been cultured in vectors. Direct diagnosis is hindered by the use of non-specific laboratory tools. Indeed, microscopic observation of Borrelia spirochaeta in smears of peripheral blood taken from febrile patients lacks sensitivity and specificity. Although best visualized using dark-field microscopy, the organisms can also be detected using Wright-Giemsa or acridine orange stains. PCR-based detection of specific sequences in total DNA extracted from a specimen can be used to discriminate different relapsing fever Borreliae. In our laboratory, we developed a multiplex real-time PCR assay for the specific detection of B. duttonii/recurrentis and B. crocidurae: multispacer sequence typing accurately identified cultured relapsing fever borreliae and revealed diversity among them. Other molecular typing techniques, such as multilocus sequence analysis of tick-borne relapsing fever borreliae, showed the potential risk of human infection in Africa. Recent efforts to culture and sequence relapsing fever borreliae have provided new information for reassessment of the diversity of these bacteria. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been reported as a means of identifying cultured borreliae and of identifying both vectors and vectorized pathogens such as detecting relapsing fever borreliae directly in ticks. The lack of a rapid diagnosis test restricts the management of such diseases. We produced monoclonal antibodies against B. crocidurae in order to develop cheap assays for the rapid detection of relapsing fever borreliae. In this paper, we

  8. [Identification of the immunogenic outer membrane proteins of relapsing fever Borrelia].

    PubMed

    Tabuchi, Norihiko; Murakami, Noritaka; Fukunaga, Masahito

    2013-01-01

    Borrelia duttonii, a causative agent of relapsing fever, is transmitted between the distinct microenvironments of the vector tick, Ornithodoros moubata, and a mammalian host. We identified the total and membrane fraction proteins of B. duttonii strain Ly isolated from a patient in Tanzania by using two-dimensional gel electrophoresis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The analyses of the total and membrane fractions from bacterial cultures incubated at 37°C identified 68 and 15 proteins, respectively. Since spirochaete clearance in mice is associated with an immunoglobulin M (IgM) and immunoglobulin G3 (IgG3)-mediated response, immunoblot analyses were used to identify the proteins reactive with IgM and IgG3 of gerbil serum against B. duttonii strain Ly. The outcome showed that six proteins (antigen p83/100, membrane-associated protein P66 (P66), flagellar filament outer layer protein, hypothetical protein BDU_412, vlp protein gamma subfamily (γ-Vlp) and flagellin (FlaB)) were identified against IgM, and four (antigen p83/100, P66, γ-Vlp and FlaB) of the six proteins also reacted with IgG3. It is believed that these proteins are immunodominant antigens for the host immune response. Some of these immunogenic proteins might be used as molecular diagnostic tools in the study of relapsing fever in Tanzania.

  9. A relapsing fever group Borrelia sp. similar to Borrelia lonestari found among wild sika deer (Cervus nippon yesoensis) and Haemaphysalis spp. ticks in Hokkaido, Japan.

    PubMed

    Lee, Kyunglee; Takano, Ai; Taylor, Kyle; Sashika, Mariko; Shimozuru, Michito; Konnai, Satoru; Kawabata, Hiroki; Tsubota, Toshio

    2014-10-01

    A relapsing fever Borrelia sp. similar to Borrelia lonestari (herein referred to as B. lonestari-like) was detected from wild sika deer (Cervus nippon yesoensis) and Haemaphysalis ticks in the eastern part of Hokkaido, Japan. The total prevalence of this Borrelia sp. in tested deer blood samples was 10.6% using conventional PCR and real-time PCR. The prevalence was significantly higher in deer fawns compared to adults (21.9% and 9.4%, respectively). Additionally, there was significant regional difference between our two sampling areas, Shiretoko and Shibetsu with 17% and 2.8% prevalence, respectively. Regional differences were also found in tick species collected from field and on deer. In the Shiretoko region, Haemaphysalis spp. were more abundant than Ixodes spp., while in Shibetsu, Ixodes spp. were more abundant. Using real-time PCR analysis, B. lonestari-like was detected from 2 out of 290 adult Haemaphysalis spp. ticks and 4 out of 76 pools of nymphs. This is the first report of a B. lonestari-like organism in Haemaphysalis spp. ticks, and the first phylogenetic analysis of this B. lonestari-like organism in Asia. Based on our results, Haemaphysalis spp. are the most likely candidates to act as a vector for B. lonestari-like; furthermore, regional variation of B. lonestari-like prevalence in sika deer may be dependent on the population distribution of these ticks. PMID:25108784

  10. Tickborne Relapsing Fever Diagnosis Obscured by Malaria, Togo

    PubMed Central

    Nordstrand, Annika; Bunikis, Ignas; Larsson, Christer; Tsogbe, Kodjo; Schwan, Tom G.; Nilsson, Mikael

    2007-01-01

    Given the prevalence of relapsing fever (RF) in Senegal, this disease may cause illness and death in other areas of West Africa. We performed a cross-sectional, clinic-based study to investigate the presence of RF in Togo during 2002–2004. Blood samples from patients with fever were examined for RF spirochetes by microscopy, PCR, and DNA sequencing of amplicons and for antibodies to the glycerophosphodiester phosphodiesterase antigen. Although no spirochetes were seen in blood smears, ≈10% of the patients were positive by PCR and ≈13% were seropositive for spirochetes. DNA sequencing demonstrated that Borrelia crocidurae and B. duttonii were present. Most patients were treated for malaria whether or not plasmodia were observed. Thus, many RF patients originally had a misdiagnosis of malaria, which resulted in ineffective treatment. The inability of microscopic analysis to detect spirochetes compared with PCR demonstrates the need for tests with greater sensitivity. PMID:17370524

  11. Insights into Borrelia miyamotoi infection from an untreated case demonstrating relapsing fever, monocytosis and a positive C6 Lyme serology.

    PubMed

    Sudhindra, Praveen; Wang, Guiqing; Schriefer, Martin E; McKenna, Donna; Zhuge, Jian; Krause, Peter J; Marques, Adriana R; Wormser, Gary P

    2016-09-01

    We describe a patient from the United States with PCR- and serology-confirmed Borrelia miyamotoi infection who recovered without antibiotics. Our findings suggest that B. miyamotoi infection may cause relapsing fever, blood monocytosis and antibody reactivity to the C6 peptide. Further studies are required to better define the spectrum of clinical and laboratory findings for this emerging tick-transmitted infection. PMID:27412815

  12. Phylogenetic analysis of the spirochetes.

    PubMed Central

    Paster, B J; Dewhirst, F E; Weisburg, W G; Tordoff, L A; Fraser, G J; Hespell, R B; Stanton, T B; Zablen, L; Mandelco, L; Woese, C R

    1991-01-01

    The 16S rRNA sequences were determined for species of Spirochaeta, Treponema, Borrelia, Leptospira, Leptonema, and Serpula, using a modified Sanger method of direct RNA sequencing. Analysis of aligned 16S rRNA sequences indicated that the spirochetes form a coherent taxon composed of six major clusters or groups. The first group, termed the treponemes, was divided into two subgroups. The first treponeme subgroup consisted of Treponema pallidum, Treponema phagedenis, Treponema denticola, a thermophilic spirochete strain, and two species of Spirochaeta, Spirochaeta zuelzerae and Spirochaeta stenostrepta, with an average interspecies similarity of 89.9%. The second treponeme subgroup contained Treponema bryantii, Treponema pectinovorum, Treponema saccharophilum, Treponema succinifaciens, and rumen strain CA, with an average interspecies similarity of 86.2%. The average interspecies similarity between the two treponeme subgroups was 84.2%. The division of the treponemes into two subgroups was verified by single-base signature analysis. The second spirochete group contained Spirochaeta aurantia, Spirochaeta halophila, Spirochaeta bajacaliforniensis, Spirochaeta litoralis, and Spirochaeta isovalerica, with an average similarity of 87.4%. The Spirochaeta group was related to the treponeme group, with an average similarity of 81.9%. The third spirochete group contained borrelias, including Borrelia burgdorferi, Borrelia anserina, Borrelia hermsii, and a rabbit tick strain. The borrelias formed a tight phylogenetic cluster, with average similarity of 97%. THe borrelia group shared a common branch with the Spirochaeta group and was closer to this group than to the treponemes. A single spirochete strain isolated fromt the shew constituted the fourth group. The fifth group was composed of strains of Serpula (Treponema) hyodysenteriae and Serpula (Treponema) innocens. The two species of this group were closely related, with a similarity of greater than 99%. Leptonema illini

  13. Association of spirochetal infection with Morgellons disease.

    PubMed

    Middelveen, Marianne J; Burugu, Divya; Poruri, Akhila; Burke, Jennie; Mayne, Peter J; Sapi, Eva; Kahn, Douglas G; Stricker, Raphael B

    2013-01-01

    Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted. PMID:24715950

  14. Association of spirochetal infection with Morgellons disease

    PubMed Central

    Stricker, Raphael B

    2013-01-01

    Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted. PMID:24715950

  15. Association of spirochetal infection with Morgellons disease.

    PubMed

    Middelveen, Marianne J; Burugu, Divya; Poruri, Akhila; Burke, Jennie; Mayne, Peter J; Sapi, Eva; Kahn, Douglas G; Stricker, Raphael B

    2013-01-01

    Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted.

  16. The flagellar cytoskeleton of the spirochetes.

    PubMed

    Wolgemuth, Charles W; Charon, Nyles W; Goldstein, Stuart F; Goldstein, Raymond E

    2006-01-01

    The recent discoveries of prokaryotic homologs of all three major eukaryotic cytoskeletal proteins (actin, tubulin, intermediate filaments) have spurred a resurgence of activity in the field of bacterial morphology. In spirochetes, however, it has long been known that the flagellar filaments act as a cytoskeletal protein structure, contributing to their shape and conferring motility on this unique phylum of bacteria. Therefore, revisiting the spirochete cytoskeleton may lead to new paradigms for exploring general features of prokaryotic morphology. This review discusses the role that the periplasmic flagella in spirochetes play in maintaining shape and producing motility. We focus on four species of spirochetes: Borrelia burgdorferi, Treponema denticola, Treponema phagedenis and Leptonema (formerly Leptospira) illini. In spirochetes, the flagella reside in the periplasmic space. Rotation of the flagella in the above species by a flagellar motor induces changes in the cell morphology that drives motility. Mutants that do not produce flagella have a markedly different shape than wild-type cells. PMID:16983197

  17. Associations of passerine birds, rabbits, and ticks with Borrelia miyamotoi and Borrelia andersonii in Michigan, U.S.A.

    PubMed Central

    2012-01-01

    Background Wild birds contribute to maintenance and dissemination of vectors and microbes, including those that impact human, domestic animal, and wildlife health. Here we elucidate roles of wild passerine birds, eastern cottontail rabbits (Sylvilagus floridanus), and Ixodes dentatus ticks in enzootic cycles of two spirochetes, Borrelia miyamotoi and B. andersonii in a region of Michigan where the zoonotic pathogen B. burgdorferi co-circulates. Methods Over a four-year period, wild birds (n = 19,631) and rabbits (n = 20) were inspected for tick presence and ear tissue was obtained from rabbits. Samples were tested for Borrelia spirochetes using nested PCR of the 16S-23S rRNA intergenic spacer region (IGS) and bidirectional DNA sequencing. Natural xenodiagnosis was used to implicate wildlife reservoirs. Results Ixodes dentatus, a tick that specializes on birds and rabbits and rarely bites humans, was the most common tick found, comprising 86.5% of the 12,432 ticks collected in the study. The relapsing fever group spirochete B. miyamotoi was documented for the first time in ticks removed from wild birds (0.7% minimum infection prevalence; MIP, in I. dentatus), and included two IGS strains. The majority of B. miyamotoi-positive ticks were removed from Northern Cardinals (Cardinalis cardinalis). Borrelia andersonii infected ticks removed from birds (1.6% MIP), ticks removed from rabbits (5.3% MIP), and rabbit ear biopsies (5%) comprised twelve novel IGS strains. Six species of wild birds were implicated as reservoirs for B. andersonii. Frequency of I. dentatus larval and nymphal co-feeding on birds was ten times greater than expected by chance. The relatively well-studied ecology of I. scapularis and the Lyme disease pathogen provides a context for understanding how the phenology of bird ticks may impact B. miyamotoi and B. andersonii prevalence and host associations. Conclusions Given the current invasion of I. scapularis, a human biting species that serves as a

  18. Chromosome and Plasmids of the Tick-Borne Relapsing Fever Agent Borrelia hermsii

    PubMed Central

    2016-01-01

    The zoonotic pathogen Borrelia hermsii bears its multiple paralogous genes for variable antigens on several linear plasmids. Application of combined long-read and short-read next-generation sequencing provided complete sequences for antigen-encoding plasmids as well as other linear and circular plasmids and the linear chromosome of the genome. PMID:27284141

  19. Lyme borreliosis spirochetes and spotted fever group rickettsiae in ixodid ticks from Pianosa island, Tuscany Archipelago, Italy.

    PubMed

    Tomassone, L; Grego, E; Auricchio, D; Iori, A; Giannini, F; Rambozzi, L

    2013-02-01

    A study on tick fauna and tick-borne pathogens was undertaken in Pianosa, an island in the Tuscany Archipelago that constitutes an important stopping and nesting point for migratory birds. Ticks were removed from feral cats and a few terrestrial birds, and host-seeking ticks were collected by dragging. A total of 89 ticks were found on animals: 57 Ixodes ventalloi Gil Collado, 1936 and 32 Ixodes acuminatus Neumann, 1901. Host-seeking ticks were 354 Hyalomma spp. larvae and 18 Hyalomma spp. adults, identified as Hyalomma marginatum C.L. Koch, 1844 (n=11) and 7 Hyalomma detritum Schulze, 1919 (n=7). A sample of adult ticks was subjected to molecular analyses to look for Rickettsia spp. and Borrelia burgdorferi sensu lato (s.l.). Sequence analysis of the 5S-23S intergenic spacer region and OspA gene of B. burgdorferi s.l.-positive samples showed the presence of Borrelia spielmanii (n=3; 3.7%, 95% confidence interval [CI] 0.08-10.4) and Borrelia valaisiana (n=13; 13.6%, 95% CI 7.0-23.0) in Ixodes ticks from cats and terrestrial birds. Ixodes spp. were also infected by Rickettsia helvetica (n=19; 23.4%, 95% CI 14.7-34.2). Finally, we detected Rickettsia aeschlimannii in 3 out of 12 host-seeking Hyalomma spp. adults tested (25%, 95% CI 5.5-57.2). Our study shows the presence of several tick-borne pathogens in Pianosa. Hyalomma spp. and Ixodes ticks other than I. ricinus seem to be involved in their epidemiological cycle, and birds could contribute to the pathogen dispersal along their migration routes. This is the first finding of B. spielmanii in Italy. We hypothesize the involvement of peridomestic rodents or hedgehogs in its maintenance in Pianosa.

  20. Mobilifilum chasei: morphology and ecology of a spirochete from an intertidal stratified microbial mat community

    NASA Technical Reports Server (NTRS)

    Margulis, L.; Hinkle, G.; Stolz, J.; Craft, F.; Esteve, I.; Guerrero, R.

    1990-01-01

    Spirochetes were found in the lower anoxiphototrophic layer of a stratified microbial mat (North Pond, Laguna Figueroa, Baja California, Mexico). Ultra-structural analysis of thin sections of field samples revealed spirochetes approximately 0.25 micrometer in diameter with 10 or more periplasmic flagella, leading to the interpretation that these spirochetes bear 10 flagellar insertions on each end. Morphometric study showed these free-living spirochetes greatly resemble certain symbiotic ones, i.e., Borrelia and certain termite spirochetes, the transverse sections of which are presented here. The ultrastructure of this spirochete also resembles Hollandina and Diplocalyx (spirochetes symbiotic in arthropods) more than it does Spirochaeta, the well known genus of mud-dwelling spirochetes. The new spirochete was detected in mat material collected both in 1985 and in 1987. Unique morphology (i.e., conspicuous outer coat of inner membrane, large number of periplasmic flagella) and ecology prompt us to name a new free-living spirochete.

  1. Ixodes ricinus spirochete and European erythema chronicum migrans disease.

    PubMed Central

    Ackermann, R.; Kabatzki, J.; Boisten, H. P.; Steere, A. C.; Grodzicki, R. L.; Hartung, S.; Runne, U.

    1984-01-01

    From three endemic locations of erythema chronicum migrans disease in North Rhine-Westphalia, Germany, we recovered 19 isolates of a spirochete from Ixodes ricinus ticks. The infection rate in adult ticks was 16 percent. The isolated spirochete is immunologically related to the Ixodes dammini spirochete, Borrelia duttoni, and Treponema pallidum. Using indirect immunofluorescence, the sera of 90 patients with erythema chronicum migrans disease showed antibody titers against the isolated spirochete, which correlated with the clinical course. Similarly, antibodies were demonstrated in the sera of 21 patients with acrodermatitis chronica atrophicans. These results suggest an etiologic role for the Ixodes ricinus spriochete in European erythema chronicum migrans disease. Images FIG. 3 PMID:6393609

  2. Lone Star Tick-Infecting Borreliae Are Most Closely Related to the Agent of Bovine Borreliosis

    PubMed Central

    Rich, Stephen M.; Armstrong, Philip M.; Smith, Ronald D.; Telford, Sam R.

    2001-01-01

    Although Borrelia theileri, the agent of bovine borreliosis, was described at the turn of the century (in 1903), its relationship with borreliae causing Lyme disease or relapsing fever remains undescribed. We tested the previously published hypothesis that spirochetes infecting Lone Star ticks (Amblyomma americanum) may comprise B. theileri by analyzing the 16S ribosomal DNAs (rDNAs) and flagellin genes of these spirochetes. B. theileri, the Amblyomma agent, and B. miyamotoi formed a natural group or clade distinct from but most closely related to that of the relapsing fever spirochetes. B. theileri and the Amblyomma agent were 97 and 98% similar at the nucleotide level within the analyzed portions of the 16S rDNA and the flagellin gene respectively, suggesting a recent divergence. The agent of bovine borreliosis might be explored as a surrogate antigen for the as-yet-uncultivatable Amblyomma agent in studies designed to explore the etiology of a Lyme disease-like infection associated with Lone Star ticks. PMID:11158095

  3. Columbian black-tailed deer (Odocoileus hemionus columbianus) as hosts for Borrelia spp. in northern California.

    PubMed

    Lane, Robert S; Mun, Jeomhee; Parker, John M; White, Marshall

    2005-01-01

    The prevalence of infection of Columbian black-tailed deer (Odocoileus hemionus columbianus) with Borrelia spp. was evaluated in an area of northwestern California (USA) where Lyme disease is endemic and the relapsing-fever group spirochete Borrelia coriaceae is enzootic, and in a far-removed comparison area having a disparate climate and lower density of vector ticks. Blood samples collected from both deer herds in 1987, 1988, and from 2000-02 were assayed for borrelial infection with microscopic and molecular methods. Serum specimens from two (5%) of 39 deer from the Dye Creek Preserve in Tehama County versus 13 (20%) of 64 animals from the Hopland Research and Extension Center (HREC) in Mendocino County, California were polymerase chain reaction (PCR) test positive for B. burgdorferi sensu lato. DNA sequencing analyses revealed that eight animals were infected with B. bissettii, six with three unclassified genotypes, and one with B. burgdorferi sensu stricto. One serum sample (2%) from HREC was positive for a relapsing-fever group spirochete that had a 16S rRNA sequence homology of 99% with the C053 type strain of B. coriaceae. Spirochetes undetermined to geno-species were detected in thick-blood drops prepared from three (8%) of 36 deer from the HREC by direct immunofluorescence. Adults of the hippoboscid flies Lipoptena depressa (n=73) and Neolipoptena ferrisi (n=24), the Pacific Coast tick (Dermacentor occidentalis) (n=22), and the western black-legged tick (Ixodes pacificus) (n=1) that had been removed from deer from both study areas in 2002 were PCR test negative for borreliae. The occurrence of diverse borreliae in deer from northern California confounds and, consequently, reduces the utility of borrelial serosurveys for detecting specific genospecies, unless they are complemented by more specific assays (e.g., immunoblotting, PCR/sequencing analysis). PMID:15827217

  4. Columbian black-tailed deer (Odocoileus hemionus columbianus) as hosts for Borrelia spp. in northern California.

    PubMed

    Lane, Robert S; Mun, Jeomhee; Parker, John M; White, Marshall

    2005-01-01

    The prevalence of infection of Columbian black-tailed deer (Odocoileus hemionus columbianus) with Borrelia spp. was evaluated in an area of northwestern California (USA) where Lyme disease is endemic and the relapsing-fever group spirochete Borrelia coriaceae is enzootic, and in a far-removed comparison area having a disparate climate and lower density of vector ticks. Blood samples collected from both deer herds in 1987, 1988, and from 2000-02 were assayed for borrelial infection with microscopic and molecular methods. Serum specimens from two (5%) of 39 deer from the Dye Creek Preserve in Tehama County versus 13 (20%) of 64 animals from the Hopland Research and Extension Center (HREC) in Mendocino County, California were polymerase chain reaction (PCR) test positive for B. burgdorferi sensu lato. DNA sequencing analyses revealed that eight animals were infected with B. bissettii, six with three unclassified genotypes, and one with B. burgdorferi sensu stricto. One serum sample (2%) from HREC was positive for a relapsing-fever group spirochete that had a 16S rRNA sequence homology of 99% with the C053 type strain of B. coriaceae. Spirochetes undetermined to geno-species were detected in thick-blood drops prepared from three (8%) of 36 deer from the HREC by direct immunofluorescence. Adults of the hippoboscid flies Lipoptena depressa (n=73) and Neolipoptena ferrisi (n=24), the Pacific Coast tick (Dermacentor occidentalis) (n=22), and the western black-legged tick (Ixodes pacificus) (n=1) that had been removed from deer from both study areas in 2002 were PCR test negative for borreliae. The occurrence of diverse borreliae in deer from northern California confounds and, consequently, reduces the utility of borrelial serosurveys for detecting specific genospecies, unless they are complemented by more specific assays (e.g., immunoblotting, PCR/sequencing analysis).

  5. Identification of conserved antigens for early serodiagnosis of relapsing fever Borrelia

    PubMed Central

    Lopez, Job E.; Porcella, Stephen F.; Schrumpf, Merry E.; Raffel, Sandra J.; Hammer, Carl H.; Zhao, Ming; Robinson, Mary Ann; Schwan, Tom G.

    2009-01-01

    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 transporter proteins, flagellar proteins, housekeeping proteins, an immune evasion protein, and proteins with unknown function. Furthermore, IgM reactivity to recombinant glycerophosphodiester phosphodiesterase was detected during early spirochaete infection and prior to a detectable IgG response. Lastly, a conserved hypothetical protein was produced in Escherichia coli and tested with immune serum against B. hermsii and Borrelia recurrentis. These results identify a much larger set of immunoreactive proteins, and could help in the early serodiagnosis of this tick-borne infection. PMID:19443544

  6. Outer membrane proteins of pathogenic spirochetes

    PubMed Central

    Cullen, Paul A.; Haake, David A.; Adler, Ben

    2009-01-01

    Pathogenic spirochetes are the causative agents of several important diseases including syphilis, Lyme disease, leptospirosis, swine dysentery, periodontal disease and some forms of relapsing fever. Spirochetal bacteria possess two membranes and the proteins present in the outer membrane are at the site of interaction with host tissue and the immune system. This review describes the current knowledge in the field of spirochetal outer membrane protein (OMP) biology. What is known concerning biogenesis and structure of OMPs, with particular regard to the atypical signal peptide cleavage sites observed amongst the spirochetes, is discussed. We examine the functions that have been determined for several spirochetal OMPs including those that have been demonstrated to function as adhesins, porins or to have roles in complement resistance. A detailed description of the role of spirochetal OMPs in immunity, including those that stimulate protective immunity or that are involved in antigenic variation, is given. A final section is included which covers experimental considerations in spirochetal outer membrane biology. This section covers contentious issues concerning cellular localization of putative OMPs, including determination of surface exposure. A more detailed knowledge of spirochetal OMP biology will hopefully lead to the design of new vaccines and a better understanding of spirochetal pathogenesis. PMID:15449605

  7. "Candidatus Borrelia kalaharica" Detected from a Febrile Traveller Returning to Germany from Vacation in Southern Africa

    PubMed Central

    Wächtler, Martin; Margos, Gabriele; Ruske, Sabine; Jung, Jette; Löscher, Thomas; Wendtner, Clemens; Wieser, Andreas

    2016-01-01

    A 26 year-old female patient presented to the Tropical Medicine outpatient unit of the Ludwig Maximilians-University in Munich with febrile illness after returning from Southern Africa, where she contracted a bite by a large mite-like arthropod, most likely a soft-tick. Spirochetes were detected in Giemsa stained blood smears and treatment was started with doxycycline for suspected tick-borne relapsing fever. The patient eventually recovered after developing a slight Jarisch-Herxheimer reaction during therapy. PCR reactions performed from EDTA-blood revealed a 16S rRNA sequence with 99.4% similarity to both, Borrelia duttonii, and B. parkeri. Further sequences obtained from the flagellin gene (flaB) demonstrated genetic distances of 0.066 and 0.097 to B. parkeri and B. duttonii, respectively. Fragments of the uvrA gene revealed genetic distance of 0.086 to B. hermsii in genetic analysis and only distant relations with classic Old World relapsing fever species. This revealed the presence of a novel species of tick-borne relapsing fever spirochetes that we propose to name “Candidatus Borrelia kalaharica”, as it was contracted from an arthropod bite in the Kalahari Desert belonging to both, Botswana and Namibia, a region where to our knowledge no relapsing fever has been described so far. Interestingly, the novel species shows more homology to New World relapsing fever Borrelia such as B. parkeri or B. hermsii than to known Old World species such as B. duttonii or B. crocidurae. PMID:27031729

  8. Borrelia persica Infection in Immunocompetent Mice - A New Tool to Study the Infection Kinetics In Vivo

    PubMed Central

    Schwarzer, Sandra; Overzier, Evelyn; Hermanns, Walter; Baneth, Gad; Straubinger, Reinhard K.

    2016-01-01

    Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 106, 1 x 104, 1 x 102 and 4 x 100 spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 106, 1 x 104 and 1 x 102 borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 104 and 1 x 102 borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species. PMID:26890814

  9. New infectious spirochete isolated from short-tailed shrews and white-footed mice.

    PubMed

    Anderson, J F; Johnson, R C; Magnarelli, L A; Hyde, F W; Andreadis, T G

    1987-08-01

    A spirochete with two periplasmic flagella was isolated from the blood or tissues of spleens and kidneys from short-tailed shrews (Blarina brevicauda) and white-footed mice (Peromyscus leucopus) in Connecticut and Minnesota. After inoculation, the shrew-mouse spirochete infected Swiss mice and Syrian hamsters. This spirochete is morphologically and serologically distinct from the species of Treponema, Borrelia, Leptospira, and Spirochaeta examined. PMID:3305565

  10. Spirochete motility and morpholgy

    NASA Astrophysics Data System (ADS)

    Charon, Nyles

    2004-03-01

    Spirochetes have a unique structure, and as a result their motility is different from that of other bacteria. These organisms can swim in a highly viscous, gel-like medium, such as that found in connective tissue, that inhibits the motility of most other bacteria. In spirochetes, the organelles for motility, the periplasmic flagella, reside inside the cell within the periplasmic space. A given periplasmic flagellum is attached only at one end of the cell, and depending on the species, may or may not overlap in the center of the cell. The number of periplasmic flagella varies from species to species. These structures have been shown to be directly involved in motility and function by rotating within the periplasmic space (1). The present talk focuses on the spirochete that causes Lyme disease, Borrelia burgdorferi. In many bacterial species, cell shape is usually dictated by the peptidoyglycan layer of the cell wall. In the first part of the talk, results will be presented that the morphology of B. burgdorferi is the result of a complex interaction between the cell cylinder and the internal periplasmic flagella resulting in a cell with a flat-wave morphology. Backward moving, propagating waves enable these bacteria to swim and translate in a given direction. Using targeted mutagenesis, we inactivated the gene encoding the major periplasmic flagellar filament protein FlaB. The resulting flaB mutants not only were non-motile, but were rod-shaped (2). Western blot analysis indicated that flaB was no longer synthesized, and electron microscopy revealed that the mutants were completely deficient in periplasmic flagella. Our results indicate that the periplasmic flagella of B. burgdorferi have a skeletal function. These organelles dynamically interact with the rod-shaped cell cylinder to enable the cell to swim, and to confer in part its flat-wave morphology The latter part of the talk concerns the basis for asymmetrical rotation of the periplasmic flagella of B

  11. Transcriptional Profiling the 150 kb Linear Megaplasmid of Borrelia turicatae Suggests a Role in Vector Colonization and Initiating Mammalian Infection

    PubMed Central

    Wilder, Hannah K.; Raffel, Sandra J.; Barbour, Alan G.; Porcella, Stephen F.; Sturdevant, Daniel E.; Vaisvil, Benjamin; Kapatral, Vinayak; Schmitt, Daniel P.; Schwan, Tom G.; Lopez, Job E.

    2016-01-01

    Adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. While plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. We utilized recent advances in genome sequencing to generate the most complete version of the Borrelia turicatae 150 kb linear megaplasmid (lp150). Additionally, a transcriptional analysis of open reading frames (ORFs) in lp150 was conducted and identified regions that were up-regulated during in vitro cultivation at tick-like growth temperatures (22°C), relative to bacteria grown at 35°C and infected murine blood. Evaluation of the 3’ end of lp150 identified a cluster of ORFs that code for putative surface lipoproteins. With a microbe’s surface proteome serving important roles in pathogenesis, we confirmed the ORFs expression in vitro and in the tick compared to spirochetes infecting murine blood. Transcriptional evaluation of lp150 indicates the plasmid likely has essential roles in vector colonization and/or initiating mammalian infection. These results also provide a much needed transcriptional framework to delineate the molecular mechanisms utilized by relapsing fever spirochetes during their enzootic cycle. PMID:26845332

  12. Blackbirds and song thrushes constitute a key reservoir of Borrelia garinii, the causative agent of borreliosis in Central Europe.

    PubMed

    Taragel'ová, Veronika; Koci, Juraj; Hanincová, Klára; Kurtenbach, Klaus; Derdáková, Markéta; Ogden, Nick H; Literák, Ivan; Kocianová, Elena; Labuda, Milan

    2008-02-01

    Blackbirds (Turdus merula) and song thrushes (Turdus philomelos) were found to carry 95% of all spirochete-infected tick larvae among 40 bird species captured in Central Europe. More than 90% of the infections were typed as Borrelia garinii and Borrelia valaisiana. We conclude that thrushes are key players in the maintenance of these spirochete species in this region of Central Europe.

  13. Tick-borne relapsing fever in North America.

    PubMed

    Dworkin, Mark S; Schwan, Tom G; Anderson, Donald E

    2002-03-01

    Relapsing fever is characterized by recurring episodes of fever and nonspecific symptoms (e.g., headache, myalgia, arthralgia, shaking chills, and abdominal complaints). The illness is caused by an infection from the Borrelia species (spirochetes) that may be acquired through the bite of an infected tick (Ornithodoros species) or contact with the hemolymph of an infected human body louse (Pediculus humanus). In North America, most cases have been acquired in the western United States, southern British Columbia, and few cases have been reported from Mexico. Most cases have been acquired from exposure to rustic tick-infested cabins and caves. This article reviews relapsing fever, especially tick-borne relapsing fever in North America. PMID:11982310

  14. Borrelia persica Infection in Immunocompetent Mice--A New Tool to Study the Infection Kinetics In Vivo.

    PubMed

    Schwarzer, Sandra; Overzier, Evelyn; Hermanns, Walter; Baneth, Gad; Straubinger, Reinhard K

    2016-02-01

    Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 10(6), 1 x 10(4), 1 x 10(2) and 4 x 10(0) spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 10(6), 1 x 10(4) and 1 x 10(2) borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 10(4) and 1 x 10(2) borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species.

  15. The unique paradigm of spirochete motility and chemotaxis

    PubMed Central

    Charon, Nyles W.; Cockburn, Andrew; Li, Chunhao; Liu, Jun; Miller, Kelly A.; Miller, Michael R.; Motaleb, Md.; Wolgemuth, Charles W.

    2013-01-01

    Spirochete motility is enigmatic: It differs from the motility of most other bacteria in that the entire bacterium is involved in translocation in the absence of external appendages. Using the Lyme disease spirochete Borrelia burgdorferi (Bb) as a model system, we explore the current research on spirochete motility and chemotaxis. Bb has periplasmic flagella (PFs) subterminally attached to each end of the protoplasmic cell cylinder, and surrounding the cell is an outer membrane. These internal helically shaped PFs allow the spirochete to swim by generating backward-moving waves by rotation. Exciting advances using cryoelectron microscopy tomography are presented with respect to in situ analysis of cell, PF, and motor structure. In addition, advances in the dynamics of motility, chemotaxis, gene regulation, and the role of motility and chemotaxis in the life cycle of Bb are summarized. The results indicate that the motility paradigms of flagellated bacteria do not apply to these unique bacteria. PMID:22994496

  16. The unique paradigm of spirochete motility and chemotaxis.

    PubMed

    Charon, Nyles W; Cockburn, Andrew; Li, Chunhao; Liu, Jun; Miller, Kelly A; Miller, Michael R; Motaleb, Md A; Wolgemuth, Charles W

    2012-01-01

    Spirochete motility is enigmatic: It differs from the motility of most other bacteria in that the entire bacterium is involved in translocation in the absence of external appendages. Using the Lyme disease spirochete Borrelia burgdorferi (Bb) as a model system, we explore the current research on spirochete motility and chemotaxis. Bb has periplasmic flagella (PFs) subterminally attached to each end of the protoplasmic cell cylinder, and surrounding the cell is an outer membrane. These internal helix-shaped PFs allow the spirochete to swim by generating backward-moving waves by rotation. Exciting advances using cryoelectron tomography are presented with respect to in situ analysis of cell, PF, and motor structure. In addition, advances in the dynamics of motility, chemotaxis, gene regulation, and the role of motility and chemotaxis in the life cycle of Bb are summarized. The results indicate that the motility paradigms of flagellated bacteria do not apply to these unique bacteria.

  17. Comparison of Growth of Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi Sensu Stricto at Five Different Temperatures

    PubMed Central

    Veinović, Gorana; Ružić-Sabljić, Eva; Strle, Franc; Cerar, Tjaša

    2016-01-01

    Lyme borreliosis is caused by the spirochete Borrelia burgdorferi sensu lato, a fastidious bacterium that replicates slowly and requires special conditions to grow in the laboratory. Borrelia isolation from clinical material is a golden standard for microbiological diagnosis of borrelial infection. Important factors that affect in vitro borrelia growth are temperature of incubation and number of borrelia cells in the sample. The aim of the study was to assess the influence of temperature on borrelia growth and survival by evaluation and comparison of growth of 31 different borrelia strains at five different temperatures and to determine the influence of different inoculums on borrelia growth at different temperatures. Borreliae were cultured in the MKP medium; the initial and final number of spirochetes was determined by dark field microscopy using Neubauer counting chamber. The growth of borrelia was defined as final number of cells/mL after three days of incubation. For all three Borrelia species, the best growth was found at 33°C, followed by 37, 28, and 23°C, while no growth was detected at 4°C (P<0.05). The growth of B. afzelii species was weaker in comparison to the other two species at 23, 28, 33 and 37°C (P<0.05), respectively. There was no statistically significant difference between the growth of B. garinii and B. burgdorferi sensu stricto at 28, 33, and 37°C (P>0.05), respectively. Inoculum had statistically significant influence on growth of all three Borrelia species at all tested temperatures except at 4°C. PMID:27310556

  18. DNA characterization of Lyme disease spirochetes.

    PubMed Central

    Schmid, G. P.; Steigerwalt, A. G.; Johnson, S.; Barbour, A. G.; Steere, A. C.; Robinson, I. M.; Brenner, D. J.

    1984-01-01

    Lyme disease spirochetes (LDS) have phenotypic characteristics of both treponemes and borreliae. To ascertain whether one or more species of LDS exist, as well as their taxonomic status, we determined the DNA base (G + C) content for three strains of LDS, the DNA relatedness of ten strains isolated in the United States or Europe, and the DNA relatedness of LDS to other spirochetes. The G + C content of the three LDS strains was 28.1-29.0 mol%, most similar to those of Borellia hermsii (30.6 mol %) and Treponema hyodysenteriae (25.6 mol %) among the other spirochetes tested. DNA hybridization studies of nine LDS strains to a reference strain isolated from human blood revealed divergence (unpaired bases) within related nucleotide sequences of only 0.0-1.0 percent, indicating the strains were one species. Similarly, relatedness values of seven strains to the reference strain were high: 58-98 percent (mean, 71 percent) in 50 degrees C reactions and 50-93 percent (mean, 69 percent) in 65 degrees C reactions. Labeled DNA from B. hermsii was 30-40 percent related to three Lyme disease spirochete strains in 50 degrees C reactions and 8-10 percent related in 65 degrees C reactions. In contrast, DNA from the reference LDS strain showed relatedness of only 1 percent to DNAs of two leptospires and only 16 percent to DNA from T. hyodysenteriae. We conclude that LDS are a single species, genetically unlike treponemes or leptospires, which belong in the genus Borrelia. PMID:6516455

  19. Investigations on the mode and dynamics of transmission and infectivity of Borrelia burgdorferi sensu stricto and Borrelia afzelii in Ixodes ricinus ticks.

    PubMed

    Crippa, Mara; Rais, Olivier; Gern, Lise

    2002-01-01

    Borrelia burgdorferi sensu lato (sl), the agent of Lyme disease, is transmitted to the host during the blood meal of Ixodes ticks. In most unfed ticks, spirochetes are present in the midgut and migrate during blood feeding to the salivary glands, from which they are transmitted to the host via saliva. In the present study, the efficiency of Ixodes ricinus ticks to transmit B. afzelii and B. burgdorferi sensu stricto (ss) and their infectivity for mice were examined in relation to the duration of the blood meal. In addition, we investigated whether these two Borrelia species can penetrate intact skin. Three modes of infection of mice were studied: tick-bite infection, inoculation of tick homogenates, and transcutaneous infection by topical application of tick homogenates on mouse skin. Transmission of B. burgdorferi sl from I. ricinus nymphs to mouse increased with duration of tick attachment. B. afzelii-infected ticks start to transmit infection earlier (< or = 48 h) than B. burgdorferi ss-infected ticks. As previously shown for B. burgdorferi ss in Ixodes scapularis, B. burgdorferi ss and B. afzelii in unfed I. ricinus were noninfectious for mice when tick homogenates were inoculated. However, the inoculation of homogenates of ticks fed for 24 h readily produced infection in mice. Therefore, B. burgdorferi ss and B. afzelii spirochetes are potentially infectious in the tick before natural transmission can occur. None of the mice (n = 33) became infected by transcutaneous transmission when tick homogenates were applied on mouse skin, showing that B. burgdorferi ss and B. afzelii are unable to penetrate intact skin, in contrast to relapsing fever spirochetes. This study also shows that B. afzelii is transmitted by I. ricinus to the host earlier than B. burgdorferi ss and that I. ricinus seems to be a more efficient vector of B. afzelii than B. burgdorferi ss.

  20. Flagellar motility of the pathogenic spirochetes.

    PubMed

    Wolgemuth, Charles W

    2015-10-01

    Bacterial pathogens are often classified by their toxicity and invasiveness. The invasiveness of a given bacterium is determined by how capable the bacterium is at invading a broad range of tissues in its host. Of mammalian pathogens, some of the most invasive come from a group of bacteria known as the spirochetes, which cause diseases, such as syphilis, Lyme disease, relapsing fever and leptospirosis. Most of the spirochetes are characterized by their distinct shapes and unique motility. They are long, thin bacteria that can be shaped like flat-waves, helices, or have more irregular morphologies. Like many other bacteria, the spirochetes use long, helical appendages known as flagella to move; however, the spirochetes enclose their flagella in the periplasm, the narrow space between the inner and outer membranes. Rotation of the flagella in the periplasm causes the entire cell body to rotate and/or undulate. These deformations of the bacterium produce the force that drives the motility of these organisms, and it is this unique motility that likely allows these bacteria to be highly invasive in mammals. This review will describe the current state of knowledge on the motility and biophysics of these organisms and provide evidence on how this knowledge can inform our understanding of spirochetal diseases. PMID:26481969

  1. Flagellar motility of the pathogenic spirochetes

    PubMed Central

    Wolgemuth, Charles W.

    2016-01-01

    Bacterial pathogens are often classified by their toxicity and invasiveness. The invasiveness of a given bacterium is determined by how capable the bacterium is at invading a broad range of tissues in its host. Of mammalian pathogens, some of the most invasive come from a group of bacteria known as the spirochetes, which cause diseases such as syphilis, Lyme disease, relapsing fever and leptospirosis. Most of the spirochetes are characterized by their distinct shapes and unique motility. They are long, thin bacteria that can be shaped like flat-waves, helices, or have more irregular morphologies. Like many other bacteria, the spirochetes use long, helical appendages known as flagella to move; however, the spirochetes enclose their flagella in the periplasm, the narrow space between the inner and outer membranes. Rotation of the flagella in the periplasm causes the entire cell body to rotate and/or undulate. These deformations of the bacterium produce the force that drives the motility of these organisms, and it is this unique motility that likely allows these bacteria to be highly invasive in mammals. This review will describe the current state of knowledge on the motility and biophysics of these organisms and provide evidence on how this knowledge can inform our understanding of spirochetal diseases. PMID:26481969

  2. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    PubMed Central

    Casjens, Sherwood R.; Mongodin, Emmanuel F.; Qiu, Wei-Gang; Dunn, John J.; Luft, Benjamin J.; Fraser-Liggett, Claire M.; Schutzer, Steve E.

    2011-01-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04. PMID:22123755

  3. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    SciTech Connect

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  4. DNA characterization of the spirochete that causes Lyme disease.

    PubMed Central

    Schmid, G P; Steigerwalt, A G; Johnson, S E; Barbour, A G; Steere, A C; Robinson, I M; Brenner, D J

    1984-01-01

    Lyme disease, a tick-borne disease long recognized in Europe but only recently recognized in the United States, was shown in 1982-1983 to be caused by a spirochete, the Lyme disease spirochete. Whether one or more species of the spirochete exists is unknown, as is its taxonomic status. To answer these questions, we determined (i) the DNA base (guanidine-plus-cytosine) content for five strains; (ii) the DNA relatedness of 10 strains from Europe or the United States (isolated from ticks, humans, and a mouse) by DNA hybridization (hydroxyapatite assay at 50 and 65 degrees C); and (iii) the DNA relatedness to other pathogenic spirochetes. The guanine-plus-cytosine content of the Lyme disease spirochete strains was 27.5 to 29.0 mol%, most similar to those of Borrelia hermsii (30.6 mol%) and Treponema hyodysenteriae (25.6 mol%) among the other spirochetes tested. DNA hybridization studies with 32P-labeled DNA from Lyme disease spirochete strain TLO-005, a human blood isolate, revealed divergence (unpaired bases) within related nucleotide sequences of only 0.0 to 1.0% for all nine Lyme disease spirochete strains tested for relatedness to TLO-005. Relatedness values of seven strains to TLO-005 were 58 to 98% (mean, 71%) in 50 degrees C reactions and 50 to 93% (mean, 69%) in 65 degrees C reactions. Two other strains, from which very low yields of DNA were obtained, showed less relatedness (36 to 50 degrees C, 38 to 47% at 65 degrees C). These were nonetheless considered to belong to the same species because of the low amount of divergence in the sequences related to TLO-005 and the absence of decreased relatedness in reactions done at 65 degrees Celsius compared with those done at 50 degrees Celsius. DNA from strain TLO-005 showed relatedness of 1% to DNAs of two leptospires and 16% relatedness to DNA from T. hyodysenteriae. B. hermsii DNA was 30 to 40% related to three Lyme disease spirochete strains in 50 degrees Celsius reactions. Divergence in these reactions was 16

  5. Isolation and characterization of Borrelia burgdorferi from Illinois Ixodes dammini.

    PubMed

    Nelson, J A; Bouseman, J K; Kitron, U; Callister, S M; Harrison, B; Bankowski, M J; Peeples, M E; Newton, B J; Anderson, J F

    1991-08-01

    Ixodes dammini ticks from two northwestern Illinois sites were found to be infected with Borrelia burgdorferi at rates of 19 and 32%. B. burgdorferi isolates, one from each site, had protein and antigenic patterns similar to those of the B-31 strain. An indirect immunofluorescence method proved to be more sensitive than dark-field microscopy in detection of these spirochetes. A modified BSK medium containing rifampin was found to be more efficient for spirochete isolation than unsupplemented BSK medium. PMID:1761698

  6. Notes from the Field: Tickborne Relapsing Fever Outbreak at an Outdoor Education Camp - Arizona, 2014.

    PubMed

    Jones, Jefferson M; Schumacher, Mare; Peoples, Marie; Souders, Nina; Horn, Kimberly; Fox, Lisa; Scott, Michele; Brady, Shane; Weiss, Joli; Komatsu, Ken; Nieto, Nathan

    2015-06-19

    Tickborne relapsing fever (TBRF) is a bacterial infection characterized by recurring episodes of fever, headache, muscle and joint aches, and nausea. In North America, TBRF primarily is caused by Borrelia hermsii spirochetes transmitted by Ornithodoros hermsii ticks. Once infected, these soft ticks are infectious for life and transmit the spirochete to sleeping humans quickly (possibly within 30 seconds) during short feeds (15-90 minutes). On August 10, 2014, the Coconino County Public Health Services District in Arizona was notified by a local hospital that five high school students who attended the same outdoor education camp had been hospitalized with fever, headache, and myalgias. Hantavirus infection initially was suspected because of reported exposure to rodent droppings, but after detecting spirochetes on peripheral blood smears from all five hospitalized students, TBRF was diagnosed. The camp was instructed to close immediately, and the health department, in collaboration with local university experts, investigated to identify additional cases, determine the cause, and prevent further infections. A total of 11 cases (six confirmed and five probable) were identified.

  7. Accelerated infectivity of tick-transmitted Lyme disease spirochetes to vector ticks.

    PubMed

    Shih, C M; Liu, L P

    1996-09-01

    We determined whether the span of infectivity of Lyme disease spirochetes (Borrelia burgdorferi) to vector ticks varies with the mode of infection in laboratory mice. Noninfected larval deer ticks were permitted to feed on two strains of spirochete-infected mice that had been naturally (via tick bite) and parenterally (via needle injection) infected with B. burgdorferi 2, 4, or 8 weeks earlier, and engorged ticks were dissected and examined for spirochetes by direct immunofluorescence microscopy. After initial infection, spirochetal infectivity to ticks was less efficient in needle-infected mice than in mice infected via tick bites. Tick-transmitted spirochetes develop more rapidly from the skin of infected mice and do not induce a strong antispirochete antibody response during the early stage of infection.

  8. The Epidemiology and Geographic Distribution of Relapsing Fever Borreliosis in West and North Africa, with a Review of the Ornithodoros erraticus Complex (Acari: Ixodida)

    PubMed Central

    Trape, Jean-François; Diatta, Georges; Arnathau, Céline; Bitam, Idir; Sarih, M’hammed; Belghyti, Driss; Bouattour, Ali; Elguero, Eric; Vial, Laurence; Mané, Youssouph; Baldé, Cellou; Pugnolle, Franck; Chauvancy, Gilles; Mahé, Gil; Granjon, Laurent; Duplantier, Jean-Marc

    2013-01-01

    Background Relapsing fever is the most frequent bacterial disease in Africa. Four main vector / pathogen complexes are classically recognized, with the louse Pediculus humanus acting as vector for B. recurrentis and the soft ticks Ornithodoros sonrai, O. erraticus and O. moubata acting as vectors for Borrelia crocidurae, B. hispanica and B. duttonii, respectively. Our aim was to investigate the epidemiology of the disease in West, North and Central Africa. Methods And Findings From 2002 to 2012, we conducted field surveys in 17 African countries and in Spain. We investigated the occurrence of Ornithodoros ticks in rodent burrows in 282 study sites. We collected 1,629 small mammals that may act as reservoir for Borrelia infections. Using molecular methods we studied genetic diversity among Ornithodoros ticks and Borrelia infections in ticks and small mammals. Of 9,870 burrows investigated, 1,196 (12.1%) were inhabited by Ornithodoros ticks. In West Africa, the southern and eastern limits of the vectors and Borrelia infections in ticks and small mammals were 13°N and 01°E, respectively. Molecular studies revealed the occurrence of nine different Ornithodoros species, including five species new for science, with six of them harboring Borrelia infections. Only B. crocidurae was found in West Africa and three Borrelia species were identified in North Africa: B. crocidurae, B. hispanica, and B. merionesi. Conclusions Borrelia Spirochetes responsible for relapsing fever in humans are highly prevalent both in Ornithodoros ticks and small mammals in North and West Africa but Ornithodoros ticks seem absent south of 13°N and small mammals are not infected in these regions. The number of Ornithodoros species acting as vector of relapsing fever is much higher than previously known. PMID:24223812

  9. Prevalence of Borrelia miyamotoi in Ixodes Ticks in Europe and the United States

    PubMed Central

    Crowder, Chris D.; Carolan, Heather E.; Rounds, Megan A.; Honig, Vaclav; Mothes, Benedikt; Haag, Heike; Nolte, Oliver; Luft, Ben J.; Grubhoffer, Libor; Ecker, David J.; Schutzer, Steven E.

    2014-01-01

    Borrelia miyamotoi, a relapsing fever-related spirochete transmitted by Ixodes ticks, has been recently shown to be a human pathogen. To characterize the prevalence of this organism in questing Ixodes ticks, we tested 2,754 ticks for a variety of tickborne pathogens by PCR and electrospray-ionization mass spectrometry. Ticks were collected from California, New York, Connecticut, Pennsylvania, and Indiana in the United States and from Germany and the Czech Republic in Europe from 2008 through 2012. In addition, an isolate from Japan was characterized. We found 3 distinct genotypes, 1 for North America, 1 for Europe, and 1 for Japan. We found B. miyamotoi infection in ticks in 16 of the 26 sites surveyed, with infection prevalence as high as 15.4%. These results show the widespread distribution of the pathogen, indicating an exposure risk to humans in areas where Ixodes ticks reside. PMID:25280366

  10. Detection of Borrelia burgdorferi and Borrelia lonestari in birds in Tennessee.

    PubMed

    Jordan, B E; Onks, K R; Hamilton, S W; Hayslette, S E; Wright, S M

    2009-01-01

    Lyme disease in the United States is caused by the bacterial spirochete Borrelia burgdorferi s.s. (Johnson, Schmid, Hyde, Steigerwalt, and Brenner), which is transmitted by tick vectors Ixodes scapularis (Say) and I. pacificus (Cooley and Kohls). Borrelia lonestari, transmitted by the tick Amblyomma americanum L., may be associated with a related syndrome, southern tick-associated rash illness (STARI). Borrelia lonestari sequences, reported primarily in the southeastern states, have also been detected in ticks in northern states. It has been suggested that migratory birds may have a role in the spread of Lyme disease spirochetes. This study evaluated both migratory waterfowl and nonmigratory wild turkeys (Meleagris gallopavo silvestris, Eastern wild turkey) for B. burgdorferi and B. lonestari DNA sequences. A total of 389 avian blood samples (163 migratory birds representing six species, 125 wild turkeys harvested in habitats shared with migratory birds, 101 wild turkeys residing more distant from migratory flyways) were extracted, amplified, and probed to determine Borrelia presence and species identity. Ninety-one samples were positive for Borrelia spp. Among migratory birds and turkeys collected near migration routes, B. burgdorferi predominated. Among turkeys residing further away from flyways, detection of B. lonestari was more common. All A. americanum ticks collected from these areas were negative for Borrelia DNA; no I. scapularis were found. To our knowledge, this represents the first documentation of B. lonestari among any birds.

  11. Tick-borne Relapsing Fever in Children in the North-west of Iran, Qazvin.

    PubMed

    Ayazi, Parviz; Mahyar, Abolfazl; Oveisi, Sonia; Esmailzadehha, Neda; Nooroozi, Sadralnesa

    2015-01-01

    Relapsing fever is caused by the Borrelia species of spirochetes. Louse-borne epidemics of the disease may happen but the endemic disease is generally transmitted to humans by the bite of an infected tick (Ornithodorus). Clinical and laboratory findings of tick-borne relapsing fever in children in the north-west of Iran, Qazvin, were evaluated. This study was conducted from September 1992 to September 2012. Records from 53 cases of tick-borne relapsing fever (TBRF) were reviewed. In positive cases, febrile illness, and spirochetes were recognized in peripheral blood preparations. Of the 53 children younger than 12 years, fifty two percent were male and about one third (34%) of the patients were in the age range of 7-12 years. The disease is recorded through the whole year but its peak occurs during summer (52.8%) and autumn (32.1%). Sixty eight percent of patients were living in urban areas but had frequent travel to rural area. Thirty two percent of the cases were living in rural areas where their dwellings were close to animal shelters. All (100%) of the 53 subjects were febrile. Travellers to the rural areas with high prevalence of the disease should be attentive of the risk of tick-borne relapsing fever and use suitable control measures. Consequently relapsing fever should be considered when patients who live in or have vacationed in north-west of Iran show a recurring febrile illness. PMID:26445390

  12. Crystal Structure of Neurotropism-Associated Variable Surface Protein 1 (VSP1) of Borrelia Turicatae

    SciTech Connect

    Lawson,C.; Yung, B.; Barbour, A.; Zuckert, W.

    2006-01-01

    Vsp surface lipoproteins are serotype-defining antigens of relapsing fever spirochetes that undergo multiphasic antigenic variation to allow bacterial persistence in spite of an immune response. Two isogenic serotypes of Borrelia turicatae strain Oz1 differ in their Vsp sequences and in disease manifestations in infected mice: Vsp1 is associated with the selection of a neurological niche, while Vsp2 is associated with blood and skin infection. We report here crystal structures of the Vsp1 dimer at 2.7 and 2.2 Angstroms. The structures confirm that relapsing fever Vsp proteins share a common helical fold with OspCs of Lyme disease-causing Borrelia. The fold features an inner stem formed by highly conserved N and C termini and an outer 'dome' formed by the variable central residues. Both Vsp1 and OspC structures possess small water-filled cavities, or pockets, that are lined largely by variable residues and are thus highly variable in shape. These features appear to signify tolerance of the Vsp-OspC fold for imperfect packing of residues at its antigenic surface. Structural comparison of Vsp1 with a homology model for Vsp2 suggests that observed differences in disease manifestation may arise in part from distinct differences in electrostatic surface properties; additional predicted positively charged surface patches on Vsp2 compared to Vsp1 may be sufficient to explain the relative propensity of Vsp2 to bind to acidic glycosaminoglycans.

  13. Seasonal Prevalence of Lyme Disease Spirochetes in a Heterothermic Mammal, the Edible Dormouse (Glis glis)

    PubMed Central

    Fietz, Joanna; Tomiuk, Jürgen; Matuschka, Franz-Rainer

    2014-01-01

    In Europe, dormice serve as competent reservoir hosts for particular genospecies of the tick-borne agent of Lyme disease (LD) and seem to support them more efficiently than do mice or voles. The longevity of edible dormice (Glis glis) and their attractiveness for ticks may result in a predominance of LD spirochetes in ticks questing in dormouse habitats. To investigate the role of edible dormice in the transmission cycle of LD spirochetes, we sampled skin tissue from the ear pinnae of dormice inhabiting five different study sites in south western Germany. Of 501 edible dormice, 12.6% harbored DNA of LD spirochetes. Edible dormice were infected most frequently with the pathogenic LD spirochete Borrelia afzelii. The DNA of B. garinii and B. bavariensis was detected in ca. 0.5% of the examined individuals. No spirochetal DNA was detectable in the skin of edible dormice until July, 6 weeks after they generally start to emerge from their obligate hibernation. Thereafter, the prevalence of spirochetal DNA in edible dormice increased during the remaining period of their 4 to 5 months of activity, reaching nearly 40% in September. Males were more than four times more likely to harbor LD spirochetes than females, and yearlings were almost twice more likely to be infected than adults. The seasonality of the prevalence of LD spirochetes in edible dormice was pronounced and may affect their role as a reservoir host in respect to other hosts. PMID:24705325

  14. Seasonal prevalence of Lyme disease spirochetes in a heterothermic mammal, the edible dormouse (Glis glis).

    PubMed

    Fietz, Joanna; Tomiuk, Jürgen; Matuschka, Franz-Rainer; Richter, Dania

    2014-06-01

    In Europe, dormice serve as competent reservoir hosts for particular genospecies of the tick-borne agent of Lyme disease (LD) and seem to support them more efficiently than do mice or voles. The longevity of edible dormice (Glis glis) and their attractiveness for ticks may result in a predominance of LD spirochetes in ticks questing in dormouse habitats. To investigate the role of edible dormice in the transmission cycle of LD spirochetes, we sampled skin tissue from the ear pinnae of dormice inhabiting five different study sites in south western Germany. Of 501 edible dormice, 12.6% harbored DNA of LD spirochetes. Edible dormice were infected most frequently with the pathogenic LD spirochete Borrelia afzelii. The DNA of B. garinii and B. bavariensis was detected in ca. 0.5% of the examined individuals. No spirochetal DNA was detectable in the skin of edible dormice until July, 6 weeks after they generally start to emerge from their obligate hibernation. Thereafter, the prevalence of spirochetal DNA in edible dormice increased during the remaining period of their 4 to 5 months of activity, reaching nearly 40% in September. Males were more than four times more likely to harbor LD spirochetes than females, and yearlings were almost twice more likely to be infected than adults. The seasonality of the prevalence of LD spirochetes in edible dormice was pronounced and may affect their role as a reservoir host in respect to other hosts.

  15. Forces and Torques on Rotating Spirochete Flagella

    NASA Astrophysics Data System (ADS)

    Yang, Jing; Huber, Greg; Wolgemuth, Charles W.

    2011-12-01

    Spirochetes are a unique group of motile bacteria that are distinguished by their helical or flat-wave shapes and the location of their flagella, which reside within the tiny space between the bacterial cell wall and the outer membrane (the periplasm). In Borrelia burgdorferi, rotation of the flagella produces cellular undulations that drive swimming. How these shape changes arise due to the forces and torques that act between the flagella and the cell body is unknown. It is possible that resistive forces come from friction or from fluid drag, depending on whether or not the flagella are in contact with the cell wall. Here, we consider both of these cases. By analyzing the motion of an elastic flagellum rotating in the periplasmic space, we show that the flagella are most likely separated from the bacterial cell wall by a lubricating layer of fluid. This analysis then provides drag coefficients for rotation and sliding of a flagellum within the periplasm.

  16. Swimming Dynamics of the Lyme Disease Spirochete

    NASA Astrophysics Data System (ADS)

    Vig, Dhruv K.; Wolgemuth, Charles W.

    2012-11-01

    The Lyme disease spirochete, Borrelia burgdorferi, swims by undulating its cell body in the form of a traveling flat wave, a process driven by rotating internal flagella. We study B. burgdorferi’s swimming by treating the cell body and flagella as linearly elastic filaments. The dynamics of the cell are then determined from the balance between elastic and resistive forces and moments. We find that planar, traveling waves only exist when the flagella are effectively anchored at both ends of the bacterium and that these traveling flat waves rotate as they undulate. The model predicts how the undulation frequency is related to the torque from the flagellar motors and how the stiffness of the cell body and flagella affect the undulations and morphology.

  17. Forces and Torques on Rotating Spirochete Flagella

    PubMed Central

    Yang, Jing; Huber, Greg; Wolgemuth, Charles W.

    2012-01-01

    Spirochetes are a unique group of motile bacteria that are distinguished by their helical or flat-wave shapes and the location of their flagella, which reside within the tiny space between the bacterial cell wall and the outer membrane (the periplasm). In Borrelia burgdorferi, rotation of the flagella produces cellular undulations that drive swimming. How these shape changes arise due to the forces and torques that act between the flagella and the cell body is unknown. It is possible that resistive forces come from friction or from fluid drag, depending on whether or not the flagella are in contact with the cell wall. Here, we consider both of these cases. By analyzing the motion of an elastic flagellum rotating in the periplasmic space, we show that the flagella are most likely separated from the bacterial cell wall by a lubricating layer of fluid. This analysis then provides drag coefficients for rotation and sliding of a flagellum within the periplasm. PMID:22243185

  18. Differential associations of Borrelia species with European badgers (Meles meles) and raccoon dogs (Nyctereutes procyonoides) in western Poland.

    PubMed

    Wodecka, Beata; Michalik, Jerzy; Lane, Robert S; Nowak-Chmura, Magdalena; Wierzbicka, Anna

    2016-07-01

    European badgers and raccoon dogs and their associated ticks and lice were assayed for the presence of Lyme borreliosis and relapsing fever-group spirochete DNA in western Poland. Analyses of blood, ear-biopsy and liver samples revealed that 25% of 28 raccoon dogs and 12% of 34 badgers were PCR positive for borreliae. Borrelia garinii was the dominant species in raccoon dogs (62.5%), followed by B. afzelii (25%) and B. valaisiana (12.5%). PCR-positive badgers were infected only with B. afzelii. A total of 351 attached ticks was recovered from 23 (82%) of the raccoon dogs and 13 (38%) of the badgers. Using a nested PCR targeting the ITS2 fragments of Ixodes DNA, four Ixodes species were identified: I. ricinus, I. canisuga, I. hexagonus, and one provisionally named I. cf. kaiseri. Ixodes canisuga and I. ricinus prevailed on both host species. The highest infection prevalence was detected in I. ricinus, followed by I. canisuga and I. cf. kaiseri. Borrelia garinii and B. afzelii accounted for 61.6% and 30.1% of the infections detected in all PCR-positive ticks, respectively. Four other Borrelia species (B. burgdorferi sensu stricto, B. valaisiana, B. lusitaniae and B. miyamotoi) were detected only in I. ricinus from raccoon dogs. Moreover, Borrelia DNA, mostly B. garinii, was detected in 57 (81.4%) of 70 Trichodectes melis lice derived from 12 badgers. The detection of B. afzelii in one-half of PCR-positive biopsies reconfirms previous associations of this species with mammalian hosts, whereas the high prevalence of B. garinii in feeding lice and I. ricinus ticks (including larvae) demonstrates that both carnivores serve as hosts for B. garinii. The lack of B. garinii DNA in the tissues of badgers versus its prevalence in raccoon-dog biopsies, however, incriminates only the latter carnivore as a potential reservoir host. PMID:27263838

  19. Differential associations of Borrelia species with European badgers (Meles meles) and raccoon dogs (Nyctereutes procyonoides) in western Poland.

    PubMed

    Wodecka, Beata; Michalik, Jerzy; Lane, Robert S; Nowak-Chmura, Magdalena; Wierzbicka, Anna

    2016-07-01

    European badgers and raccoon dogs and their associated ticks and lice were assayed for the presence of Lyme borreliosis and relapsing fever-group spirochete DNA in western Poland. Analyses of blood, ear-biopsy and liver samples revealed that 25% of 28 raccoon dogs and 12% of 34 badgers were PCR positive for borreliae. Borrelia garinii was the dominant species in raccoon dogs (62.5%), followed by B. afzelii (25%) and B. valaisiana (12.5%). PCR-positive badgers were infected only with B. afzelii. A total of 351 attached ticks was recovered from 23 (82%) of the raccoon dogs and 13 (38%) of the badgers. Using a nested PCR targeting the ITS2 fragments of Ixodes DNA, four Ixodes species were identified: I. ricinus, I. canisuga, I. hexagonus, and one provisionally named I. cf. kaiseri. Ixodes canisuga and I. ricinus prevailed on both host species. The highest infection prevalence was detected in I. ricinus, followed by I. canisuga and I. cf. kaiseri. Borrelia garinii and B. afzelii accounted for 61.6% and 30.1% of the infections detected in all PCR-positive ticks, respectively. Four other Borrelia species (B. burgdorferi sensu stricto, B. valaisiana, B. lusitaniae and B. miyamotoi) were detected only in I. ricinus from raccoon dogs. Moreover, Borrelia DNA, mostly B. garinii, was detected in 57 (81.4%) of 70 Trichodectes melis lice derived from 12 badgers. The detection of B. afzelii in one-half of PCR-positive biopsies reconfirms previous associations of this species with mammalian hosts, whereas the high prevalence of B. garinii in feeding lice and I. ricinus ticks (including larvae) demonstrates that both carnivores serve as hosts for B. garinii. The lack of B. garinii DNA in the tissues of badgers versus its prevalence in raccoon-dog biopsies, however, incriminates only the latter carnivore as a potential reservoir host.

  20. Hide and Seek: How Lyme Disease Spirochetes Overcome Complement Attack

    PubMed Central

    Kraiczy, Peter

    2016-01-01

    Overcoming the first line of the innate immune system is a general hallmark of pathogenic microbes to avoid recognition and to enter the human host. In particular, spirochetes belonging to the Borrelia burgdorferi sensu lato complex have developed various means to counter the immune response and to successfully survive in diverse host environments for a prolonged period of time. In regard to complement resistance, Borrelia utilize a plethora of immune evasion strategies involves capturing of host-derived complement regulators, terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to expeditiously inhibit human complement. Owing to their mode of action, the interacting surface-exposed proteins identified among B. burgdorferi sensu stricto (s.s.), Borrelia afzelii, Borrelia spielmanii, and Borrelia bavariensis can be classified into at least two major categories, namely, molecules that directly interfere with distinct complement components including BBK32, CspA, BGA66, BGA71, and a CD59-like protein or molecules, which indirectly counteract complement activation by binding various complement regulators such as Factor H, Factor H-like protein 1 (FHL-1), Factor H-related proteins FHR-1, FHR-2, or C4Bp. The latter group of genetically and structurally unrelated proteins has been collectively referred to as “complement regulator-acquiring surface proteins” and consists of CspA, CspZ, ErpA, ErpC, ErpP, and the as yet unidentified protein p43. This review focuses on the current knowledge of immune evasion mechanisms exhibited by Lyme disease spirochetes and highlights the role of complement-interfering, infection-associated molecules playing an important part in these processes. Deciphering the immune evasion strategies may provide novel avenues for improved diagnostic approaches and therapeutic interventions. PMID:27725820

  1. Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp

    PubMed Central

    Goc, Anna; Niedzwiecki, Alexandra; Rath, Matthias

    2016-01-01

    Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria. PMID:27570483

  2. Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp.

    PubMed

    Goc, Anna; Niedzwiecki, Alexandra; Rath, Matthias

    2016-01-01

    Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria. PMID:27570483

  3. Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas

    PubMed Central

    Sapi, E.; Balasubramanian, K.; Poruri, A.; Maghsoudlou, J. S.; Socarras, K. M.; Timmaraju, A. V.; Filush, K. R.; Gupta, K.; Shaikh, S.; Theophilus, P. A. S.; Luecke, D. F.; MacDonald, A.; Zelger, B.

    2016-01-01

    Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. However, there is no evidence of the existence of Borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of Borrelia biofilm in infected human skin tissues. Archived skin biopsy tissues from borrelial lymphocytomas (BL) were reexamined for the presence of B. burgdorferi sensu lato using Borrelia-specific immunohistochemical staining (IHC), fluorescent in situ hybridization, combined fluorescent in situ hybridization (FISH)–IHC, polymerase chain reaction (PCR), and fluorescent and atomic force microscopy methods. Our morphological and histological analyses showed that significant amounts of Borrelia-positive spirochetes and aggregates exist in the BL tissues. Analyzing structures positive for Borrelia showed that aggregates, but not spirochetes, expressed biofilm markers such as protective layers of different mucopolysaccharides, especially alginate. Atomic force microscopy revealed additional hallmark biofilm features of the Borrelia/alginate-positive aggregates such as inside channels and surface protrusions. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in human infected skin tissues. PMID:27141311

  4. Fever

    MedlinePlus

    A fever is a body temperature that is higher than normal. It is not an illness. It is part of your body's defense against infection. Most bacteria ... cause infections do well at the body's normal temperature (98.6 F). A slight fever can make ...

  5. Sensitivity of Lyme Borreliosis Spirochetes to Serum Complement of Regular Zoo Animals: Potential Reservoir Competence of Some Exotic Vertebrates.

    PubMed

    Ticha, Lucie; Golovchenko, Maryna; Oliver, James H; Grubhoffer, Libor; Rudenko, Nataliia

    2016-01-01

    Reaction of vertebrate serum complement with different Borrelia burgdorferi sensu lato species is used as a basis in determining reservoir hosts among domesticated and wild animals. Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii were tested for their sensitivity to sera of exotic vertebrate species housed in five zoos located in the Czech Republic. We confirmed that different Borrelia species have different sensitivity to host serum. We found that tolerance to Borrelia infection possessed by hosts might differ among individuals of the same genera or species and is not affected by host age or sex. Of all zoo animals included in our study, carnivores demonstrated the highest apparent reservoir competency for Lyme borreliosis spirochetes. We showed that selected exotic ungulate species are tolerant to Borrelia infection. For the first time we showed the high tolerance of Siamese crocodile to Borrelia as compared to the other studied reptile species. While exotic vertebrates present a limited risk to the European human population as reservoirs for the causative agents of Lyme borreliosis, cases of incidental spillover infection could lead to successful replication of the pathogens in a new host, changing the status of selected exotic species and their role in pathogen emergence or maintenance. The question if being tolerant to pathogen means to be a competent reservoir host still needs an answer, simply because the majority of exotic animals might never be exposed to spirochetes in their natural environment. PMID:26783940

  6. Sensitivity of Lyme Borreliosis Spirochetes to Serum Complement of Regular Zoo Animals: Potential Reservoir Competence of Some Exotic Vertebrates.

    PubMed

    Ticha, Lucie; Golovchenko, Maryna; Oliver, James H; Grubhoffer, Libor; Rudenko, Nataliia

    2016-01-01

    Reaction of vertebrate serum complement with different Borrelia burgdorferi sensu lato species is used as a basis in determining reservoir hosts among domesticated and wild animals. Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii were tested for their sensitivity to sera of exotic vertebrate species housed in five zoos located in the Czech Republic. We confirmed that different Borrelia species have different sensitivity to host serum. We found that tolerance to Borrelia infection possessed by hosts might differ among individuals of the same genera or species and is not affected by host age or sex. Of all zoo animals included in our study, carnivores demonstrated the highest apparent reservoir competency for Lyme borreliosis spirochetes. We showed that selected exotic ungulate species are tolerant to Borrelia infection. For the first time we showed the high tolerance of Siamese crocodile to Borrelia as compared to the other studied reptile species. While exotic vertebrates present a limited risk to the European human population as reservoirs for the causative agents of Lyme borreliosis, cases of incidental spillover infection could lead to successful replication of the pathogens in a new host, changing the status of selected exotic species and their role in pathogen emergence or maintenance. The question if being tolerant to pathogen means to be a competent reservoir host still needs an answer, simply because the majority of exotic animals might never be exposed to spirochetes in their natural environment.

  7. Serologic Evidence for Borrelia hermsii Infection in Rodents on Federally Owned Recreational Areas in California

    PubMed Central

    Payne, Jessica R.; Schwan, Tom G.

    2013-01-01

    Abstract Tick-borne relapsing fever (TBRF) is endemic in mountainous regions of the western United States. In California, the principal agent is the spirochete Borrelia hermsii, which is transmitted by the argasid tick Ornithodoros hermsi. Humans are at risk of TBRF when infected ticks leave an abandoned rodent nest in quest of a blood meal. Rodents are the primary vertebrate hosts for B. hermsii. Sciurid rodents were collected from 23 sites in California between August, 2006, and September, 2008, and tested for serum antibodies to B. hermsii by immunoblot using a whole-cell sonicate and a specific antigen, glycerophosphodiester phosphodiesterase (GlpQ). Antibodies were detected in 20% of rodents; seroprevalence was highest (36%) in chipmunks (Tamias spp). Seroprevalence in chipmunks was highest in the Sierra Nevada (41%) and Mono (43%) ecoregions and between 1900 and 2300 meters elevation (43%). The serological studies described here are effective in implicating the primary vertebrate hosts involved in the maintenance of the ticks and spirochetes in regions endemic for TBRF. PMID:23488454

  8. Elimination of Borrelia burgdorferi from vector ticks feeding on OspA-immunized mice.

    PubMed

    Fikrig, E; Telford, S R; Barthold, S W; Kantor, F S; Spielman, A; Flavell, R A

    1992-06-15

    Although recombinant outer surface protein A (OspA) of Borrelia burgdorferi protects mice against injected Lyme disease spirochetes, the mode of protection has not yet been explored. Indeed, the efficacy of vaccine-induced immunity against a realistic vector-mediated challenge remains unexplored. Accordingly, we determined whether this immunogen protects mice against spirochetes delivered by nymphal Ixodes dammini ticks. Following challenge by tick bite, no spirochetes could be cultured from immunized mice, and no characteristic histopathology was found. The spirochete was not detected in ticks that fed on immunized animals and was present in virtually all ticks that fed on nonimmunized mice. We conclude that OspA-immunized mice are protected from spirochetal infection, at least in part, because the spirochete is destroyed in the infecting tick.

  9. Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy.

    PubMed

    Bockenstedt, Linda K; Gonzalez, David G; Haberman, Ann M; Belperron, Alexia A

    2012-07-01

    An enigmatic feature of Lyme disease is the slow resolution of musculoskeletal symptoms that can continue after treatment, with some patients developing an inflammatory arthritis that becomes refractory to antibiotic therapy. Using intravital microscopy and the mouse model of Lyme borreliosis, we observed that Borrelia burgdorferi antigens, but not infectious spirochetes, can remain adjacent to cartilage for extended periods after antibiotic treatment. B. burgdorferi was not recovered by culture or xenodiagnosis with ticks after antibiotic treatment of WT mice and all but one of the immunodeficient mice with heightened pathogen burden due to impaired TLR responsiveness. Amorphous GFP+ deposits were visualized by intravital microscopy in the entheses of antibiotic-treated mice infected with GFP-expressing spirochetes and on the ear cartilage surface in sites where immunofluorescence staining detected spirochete antigens. Naive mice were not infected by tissue transplants from antibiotic-treated mice even though transplants contained spirochete DNA. Tissue homogenates from antibiotic-treated mice induced IgG reactive with B. burgdorferi antigens after immunization of naive mice and stimulated TNF-α production from macrophages in vitro. This is the first direct demonstration that inflammatory B. burgdorferi components can persist near cartilaginous tissue after treatment for Lyme disease. We propose that these deposits could contribute to the development of antibiotic-refractory Lyme arthritis.

  10. Large Scale Spatial Risk and Comparative Prevalence of Borrelia miyamotoi and Borrelia burgdorferi Sensu Lato in Ixodes pacificus

    PubMed Central

    Padgett, Kerry; Bonilla, Denise; Kjemtrup, Anne; Vilcins, Inger-Marie; Yoshimizu, Melissa Hardstone; Hui, Lucia; Sola, Milagros; Quintana, Miguel; Kramer, Vicki

    2014-01-01

    Borrelia miyamotoi is a newly described emerging pathogen transmitted to people by Ixodes species ticks and found in temperate regions of North America, Europe, and Asia. There is limited understanding of large scale entomological risk patterns of B. miyamotoi and of Borreila burgdorferi sensu stricto (ss), the agent of Lyme disease, in western North America. In this study, B. miyamotoi, a relapsing fever spirochete, was detected in adult (n = 70) and nymphal (n = 36) Ixodes pacificus ticks collected from 24 of 48 California counties that were surveyed over a 13 year period. Statewide prevalence of B. burgdorferi sensu lato (sl), which includes B. burgdorferi ss, and B. miyamotoi were similar in adult I. pacificus (0.6% and 0.8%, respectively). In contrast, the prevalence of B. burgdorferi sl was almost 2.5 times higher than B. miyamotoi in nymphal I. pacificus (3.2% versus 1.4%). These results suggest similar risk of exposure to B. burgdorferi sl and B. miyamotoi from adult I. pacificus tick bites in California, but a higher risk of contracting B. burgdorferi sl than B. miyamotoi from nymphal tick bites. While regional risk of exposure to these two spirochetes varies, the highest risk for both species is found in north and central coastal California and the Sierra Nevada foothill region, and the lowest risk is in southern California; nevertheless, tick-bite avoidance measures should be implemented in all regions of California. This is the first study to comprehensively evaluate entomologic risk for B. miyamotoi and B. burgdorferi for both adult and nymphal I. pacificus, an important human biting tick in western North America. PMID:25333277

  11. Fever

    MedlinePlus

    ... of charts. A fever is defined as a temperature 1° or more above the normal 98.6°. Minor infections may cause mild or short-term temperature elevations. Temperatures of 103° and above are considered ...

  12. Reactivity of human Lyme borreliosis sera with a 39-kilodalton antigen specific to Borrelia burgdorferi.

    PubMed Central

    Simpson, W J; Schrumpf, M E; Schwan, T G

    1990-01-01

    Borrelia burgdorferi is the causative agent of Lyme borreliosis, a spirochetal illness with a variety of acute clinical manifestations that may lead to debilitating neurological and arthritic complications. Diagnosis is difficult because symptoms mimic a variety of unrelated clinical conditions, spirochetes cannot always be isolated from infected patients, and current serological tests are frequently inconclusive because of the presence of cross-reacting non-B. burgdorferi antibodies. To identify antigens specific to B. burgdorferi that could be used in the serodiagnosis of Lyme borreliosis, we screened a Borrelia DNA expression library in Escherichia coli for antigens reactive with human Lyme borreliosis sera. One clone carried a 6.3-kilobase EcoRI chromosomal fragment (pSPR33), which encoded two species-specific antigens with molecular masses of 28 (P28) and 39 (P39) kilodaltons (kDa). These two antigens were immunologically distinct from OspA, OspB, and the 41-kDa flagellin. Ninety-four serum specimens from patients having Lyme borreliosis were tested for reactivity with P39. All of 33 the serum specimens with immunofluorescence assay titers of greater than or equal to 1:256, 13 of 17 serum specimens with titers of 1:128, and 14 of 44 serum specimens with titers of less than or equal to 1:64 reacted with P39. Notably, many sera reactive to P39 did not appear to react with the 41-kDa flagellin. Therefore, antibody to P39 could be mistaken for antibody to the 41-kDa flagellin in tests of human sera by Western blot (immunoblot). Twenty-five control serum specimens, which included sera from syphilitic, relapsing fever, and amyotrophic lateral sclerosis patients as well as from 10 normal individuals, did not react to P39. Our data suggest that P39 may be a useful antigen for the serological confirmation of Lyme borreliosis. Images PMID:2380361

  13. Molecular Typing of Borrelia burgdorferi Sensu Lato: Taxonomic, Epidemiological, and Clinical Implications

    PubMed Central

    Wang, Guiqing; van Dam, Alje P.; Schwartz, Ira; Dankert, Jacob

    1999-01-01

    Borrelia burgdorferi sensu lato, the spirochete that causes human Lyme borreliosis (LB), is a genetically and phenotypically divergent species. In the past several years, various molecular approaches have been developed and used to determine the phenotypic and genetic heterogeneity within the LB-related spirochetes and their potential association with distinct clinical syndromes. These methods include serotyping, multilocus enzyme electrophoresis, DNA-DNA reassociation analysis, rRNA gene restriction analysis (ribotyping), pulsed-field gel electrophoresis, plasmid fingerprinting, randomly amplified polymorphic DNA fingerprinting analysis, species-specific PCR and PCR-based restriction fragment length polymorphism (RFLP) analysis, and sequence analysis of 16S rRNA and other conserved genes. On the basis of DNA-DNA reassociation analysis, 10 different Borrelia species have been described within the B. burgdorferi sensu lato complex: B. burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii, Borrelia japonica, Borrelia andersonii, Borrelia valaisiana, Borrelia lusitaniae, Borrelia tanukii, Borrelia turdi, and Borrelia bissettii sp. nov. To date, only B. burgdorferi sensu stricto, B. garinii, and B. afzelii are well known to be responsible for causing human disease. Different Borrelia species have been associated with distinct clinical manifestations of LB. In addition, Borrelia species are differentially distributed worldwide and may be maintained through different transmission cycles in nature. In this paper, the molecular methods used for typing of B. burgdorferi sensu lato are reviewed. The current taxonomic status of B. burgdorferi sensu lato and its epidemiological and clinical implications, especiallly correlation between the variable clinical presentations and the infecting Borrelia species, are discussed in detail. PMID:10515907

  14. High-prevalence Borrelia miyamotoi infection among [corrected] wild turkeys (Meleagris gallopavo) in Tennessee.

    PubMed

    Scott, M C; Rosen, M E; Hamer, S A; Baker, E; Edwards, H; Crowder, C; Tsao, J I; Hickling, G J

    2010-11-01

    During spring and fall 2009, 60 wild turkeys (Meleagris gallopavo) harvested by Tennessee hunters were surveyed for Borrelia spp. by sampling their blood, tissue, and attached ticks. In both seasons, 70% of turkeys were infested with juvenile Amblyomma americanum; one spring turkey hosted an adult female Ixodes brunneus. Polymerase chain reaction assays followed by DNA sequencing indicated that 58% of the turkeys were positive for the spirochete Borrelia miyamotoi, with tissue testing positive more frequently than blood (P = 0.015). Sequencing of the 16S-23S rRNA intergenic spacer indicated > or = 99% similarity to previously published sequences of the North American strain of this spirochete. Positive turkeys were present in both seasons and from all seven middle Tennessee counties sampled. No ticks from the turkeys tested positive for any Borrelia spp. This is the first report of B. miyamotoi in birds; the transmission pathways and epidemiological significance of this high-prevalence spirochetal infection remain uncertain.

  15. Borrelia burgdorferi tissue morphologies and imaging methodologies.

    PubMed

    MacDonald, A B

    2013-08-01

    This manuscript offers an image presentation of diverse forms of Borrelia burgdorferi spirochetes which are not spiral or corkscrew shaped. Explanations are offered to justify the legitimacy of tissue forms of Borrelia which may confuse the inexperienced microscopic examiner and which may lead to the misdiagnosis of non-spiral forms as artifacts. Images from the author's personal collection of Borrelia burgdorferi images and a few select images of Borrelia burgdorferi from the peer-reviewed published literature are presented. A commentary justifying each of the image profiles and a survey of the imaging modalities utilized provides the reader with a frame of reference. Regularly spiraled Borrelia are rarely seen in solid tissues. A variety of straightened, undulating, and clipped-off profiles are demonstrated, and the structural basis for each image is explained. Tissue examination is a diagnostic tool and a quality control for judging the eradication or the persistence of borreliosis following attempts to eradicate the infection with antibiotic therapy. The presence or absence of chronic Lyme borreliosis may be objectively adjudicated by tissue examinations which demonstrate or which fail to show pathogenic microbes in patients who have received a full course of antibiotics.

  16. Borrelia burgdorferi tissue morphologies and imaging methodologies.

    PubMed

    MacDonald, A B

    2013-08-01

    This manuscript offers an image presentation of diverse forms of Borrelia burgdorferi spirochetes which are not spiral or corkscrew shaped. Explanations are offered to justify the legitimacy of tissue forms of Borrelia which may confuse the inexperienced microscopic examiner and which may lead to the misdiagnosis of non-spiral forms as artifacts. Images from the author's personal collection of Borrelia burgdorferi images and a few select images of Borrelia burgdorferi from the peer-reviewed published literature are presented. A commentary justifying each of the image profiles and a survey of the imaging modalities utilized provides the reader with a frame of reference. Regularly spiraled Borrelia are rarely seen in solid tissues. A variety of straightened, undulating, and clipped-off profiles are demonstrated, and the structural basis for each image is explained. Tissue examination is a diagnostic tool and a quality control for judging the eradication or the persistence of borreliosis following attempts to eradicate the infection with antibiotic therapy. The presence or absence of chronic Lyme borreliosis may be objectively adjudicated by tissue examinations which demonstrate or which fail to show pathogenic microbes in patients who have received a full course of antibiotics. PMID:23479042

  17. Genetics of Borrelia burgdorferi

    PubMed Central

    Brisson, Dustin; Drecktrah, Dan; Eggers, Christian H.; Samuels, D. Scott

    2013-01-01

    The spirochetes in the Borrelia burgdorferi sensu lato genospecies group cycle in nature between tick vectors and vertebrate hosts. The current assemblage of B. burgdorferi sensu lato, of which three species cause Lyme disease in humans, originated from a rapid species radiation that occurred near the origin of the clade. All of these species share a unique genome structure that is highly segmented and predominantly composed of linear replicons. One of the circular plasmids is a prophage that exists as several isoforms in each cell and can be transduced to other cells, likely contributing to an otherwise relatively anemic level of horizontal gene transfer, which nevertheless appears to be adequate to permit strong natural selection and adaptation in populations of B. burgdorferi. Although the molecular genetic toolbox is meager, several antibiotic-resistant mutants have been isolated, and the resistance alleles, as well as some exogenous genes, have been fashioned into markers to dissect gene function. Genetic studies have probed the role of the outer membrane lipoprotein OspC, which is maintained in nature by multiple niche polymorphisms and negative frequency-dependent selection. One of the most intriguing genetic systems in B. burgdorferi is vls recombination, which generates antigenic variation during infection of mammalian hosts. PMID:22974303

  18. Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete

    PubMed Central

    Narasimhan, Sukanya; Rajeevan, Nallakkandi; Liu, Lei; Zhao, Yang O.; Heisig, Julia; Pan, Jingyi; Eppler-Epstein, Rebecca; DePonte, Kathleen; Fish, Durland; Fikrig, Erol

    2014-01-01

    SUMMARY Arthopods, such as Ixodes ticks, serve as vectors for many human pathogens. The arthropod gut presents a pivotal microbial entry point and determines pathogen colonization and survival. We show that the gut microbiota of Ixodes scapularis, a major vector of the Lyme disease spirochete Borrelia burgdorferi, influence spirochete colonization of ticks. Perturbing the gut microbiota of larval ticks reduced Borrelia colonization, with dysbiosed larvae displaying decreased expression of the transcription factor STAT. Diminished STAT expression corresponded to lower expression of peritrophin, a key glycoprotein scaffold of the glycan-rich mucus-like peritrophic matrix (PM) that separates the gut lumen from the epithelium. The integrity of the I. scapularis PM was essential for B. burgdorferi to efficiently colonize the gut epithelium. These data elucidate a functional link between the gut microbiota, STAT-signaling, and pathogen colonization in the context of the gut epithelial barrier of an arthropod vector. PMID:24439898

  19. Arthritis is developed in Borrelia-primed and -infected mice deficient of interleukin-17.

    PubMed

    Kuo, Joseph; Warner, Thomas F; Munson, Erik L; Nardelli, Dean T; Schell, Ronald F

    2016-10-01

    Interleukin-17 (IL-17) has been shown to participate in the development of Lyme arthritis in experimental mice. For example, neutralization of IL-17 with antibodies inhibits induction of arthritis in Borrelia-primed and -infected C57BL/6 wild-type mice. We hypothesized that mice lacking IL-17 would fail to develop Borrelia-induced arthritis. IL-17-deficient and wild-type C57BL/6 mice were primed with heat-inactivated Borrelia and then infected with viable spirochetes 3 weeks later. No swelling or major histopathological changes of the hind paws were detected in IL-17-deficient or wild-type mice that were primed with Borrelia or infected with viable spirochetes. By contrast, IL-17-deficient and wild-type mice that were primed and subsequently infected with heterologous Borrelia developed severe swelling and histopathological changes of the hind paws. In addition, Borrelia-primed and -infected IL-17-deficient mice exhibited elevated gamma-interferon (IFN-γ) levels in sera and increased frequencies of IFN-γ-expressing lymphocytes in popliteal lymph nodes compared to Borrelia-primed and -infected wild-type mice. These results demonstrate that IL-17 is not required for development of severe pathology in response to infection with Borrelia burgdorferi, but may contribute to disease through an interaction with IFN-γ. PMID:27493062

  20. Transstadial Transmission of Borrelia turcica in Hyalomma aegyptium Ticks

    PubMed Central

    Kalmár, Zsuzsa; Cozma, Vasile; Sprong, Hein; Jahfari, Setareh; D’Amico, Gianluca; Mărcuțan, Daniel I.; Ionică, Angela M.; Magdaş, Cristian; Modrý, David; Mihalca, Andrei D.

    2015-01-01

    Borrelia turcica comprises the third major group of arthropod-transmitted borreliae and is phylogenetically divergent from other Borrelia groups. The novel group of Borrelia was initially isolated from Hyalomma aegyptium ticks in Turkey and it was recently found in blood and multiple organs of tortoises exported from Jordan to Japan. However, the ecology of these spirochetes and their development in ticks or the vertebrate hosts were not investigated in detail; our aims were to isolate the pathogen and to evaluate the possibility of transstadial transmission of Borrelia turcica by H. aegyptium ticks. Ticks were collected from Testudo graeca tortoises during the summer of 2013 from southeastern Romania. Engorged nymphs were successfully molted to the adult stage. Alive B. turcica was isolated from molted ticks by using Barbour-Stoenner-Kelly (BSK) II medium. Four pure cultures of spirochetes were obtained and analyzed by PCR and sequencing. Sequence analysis of glpQ, gyrB and flaB revealed 98%–100% similarities with B. turcica. H. aegyptium ticks collected from T. graeca tortoises were able to pass the infection with B. turcica via transstadial route, suggesting its vectorial capacity. PMID:25695663

  1. Experimental Borrelia burgdorferi infection in Peromyscus leucopus.

    PubMed

    Moody, K D; Terwilliger, G A; Hansen, G M; Barthold, S W

    1994-04-01

    We evaluated the susceptibility of laboratory-reared adult and infant white-footed mice (Peromyscus leucopus) to a known pathogenic isolate of Borrelia burgdorferi (N40). Two-month-old and 3-day-old Peromyscus were inoculated intradermally with 10(6) to 10(7) spirochetes. At 21 days for adults or 30 days for infants post inoculation, mice were killed, and tissues were cultured for spirochetes and examined microscopically. Based on serology and culture, adult mice became infected but did not have any gross or microscopic lesions. Mice inoculated as infants became infected, and also developed carditis and multifocal arthritis. Contact transmission between inoculated infants and their naive mothers was not observed. Age at inoculation appeared to be a critical factor in inducing Lyme borreliosis lesions in Peromyscus leucopus, as in other species.

  2. Recognition of Borrelia burgdorferi by NOD2 is central for the induction of an inflammatory reaction.

    PubMed

    Oosting, Marije; Berende, Anneleen; Sturm, Patrick; Ter Hofstede, Hadewych J M; de Jong, Dirk J; Kanneganti, Thirumala-Devi; van der Meer, Jos W M; Kullberg, Bart-Jan; Netea, Mihai G; Joosten, Leo A B

    2010-06-15

    Toll-like receptor 2 (TLR2) plays an important role in the recognition of Borrelia bacteria, the causative agent of Lyme disease, but the existence and importance of additional receptors in this process has been hypothesized. In the present study, we confirmed the role played by TLR2 in the recognition of Borrelia bacteria but also demonstrated a crucial role for the intracellular peptidoglycan receptor NOD2 for sensing the spirochete. Cells from individuals who were homozygous for the loss-of-function mutation 3020insC in the NOD2 gene were defective with respect to cytokine release after stimulation with Borrelia species, and this was confirmed in peritoneal macrophages from mice lacking RICK, the adaptor molecule used by NOD2. In contrast, NOD1 played no major role in the recognition of Borrelia spirochetes. This raises the intriguing possibility that recognition of Borrelia spirochetes is exerted by TLR2 in combination with NOD2 and that both receptors are necessary for an effective induction of cytokines by Borrelia species. The interplay between TLR2 and NOD2 might not only be necessary for the induction of a proper immune response but may also contribute to inflammatory-induced pathology. PMID:20441518

  3. Interaction of the Lyme disease spirochete with its tick vector

    PubMed Central

    Caimano, Melissa J.; Drecktrah, Dan; Kung, Faith; Samuels, D. Scott

    2016-01-01

    Summary Borrelia burgdorferi , the causative agent of Lyme disease (along with closely related genospecies), is in the deeply branching spirochete phylum. The bacterium is maintained in nature in an enzootic cycle that involves transmission from a tick vector to a vertebrate host and acquisition from a vertebrate host to a tick vector. During its arthropod sojourn, B. burgdorferi faces a variety of stresses, including nutrient deprivation. Here, we review some of the spirochetal factors that promote persistence, maintenance and dissemination of B. burgdorferi in the tick, and then focus on the utilization of available carbohydrates as well as the exquisite regulatory systems invoked to adapt to the austere environment between blood meals and to signal species transitions as the bacteria traverse their enzootic cycle. The spirochetes shift their source of carbon and energy from glucose in the vertebrate to glycerol in the tick. Regulation of survival under limiting nutrients requires the classic stringent response in which RelBbu controls the levels of the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively termed (p)ppGpp), while regulation at the tick–vertebrate interface as well as regulation of protective responses to the blood meal require the two-component system Hk1/Rrp1 to activate production of the second messenger cyclic-dimeric-GMP (c-di-GMP). PMID:27147446

  4. Wood rats and kangaroo rats: potential reservoirs of the Lyme disease spirochete in California.

    PubMed

    Lane, R S; Brown, R N

    1991-05-01

    The etiologic agent of Lyme disease, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was isolated repeatedly from dusky-footed wood rats, Neotoma fuscipes Baird, and California kangaroo rats, Dipodomys californicus Merriam, in northern California. All animals were collected in a region endemic for Lyme disease but for which the natural reservoir of B. burgdorferi was unknown. Similar attempts to isolate spirochetes from lizards, other species of rodents, jack rabbits, and deer between 1987 and 1991 were unsuccessful. Spirochetes isolated from wood rats and kangaroo rats were antigenically similar to strains of B. burgdorferi that had been isolated previously from the western black-legged tick, Ixodes pacificus Cooley & Kohls, in California. Similar enzootic cycles involving wood rats or kangaroo rats should be sought in other regions of the United States where the reservoirs of this spirochete are unknown.

  5. Composite, large spirochetes from microbial mats: spirochete structure review

    NASA Technical Reports Server (NTRS)

    Margulis, L.; Ashen, J. B.; Sole, M.; Guerrero, R.

    1993-01-01

    Phenomena previously unknown in free-living spirochetes are reported: large-sized cells with variable diameter (length to 100 microns, width between 0.4 and 3.0 microns), composite structure (smaller spirochetes inside larger ones), and positive phototropic behavior. These bacteria, Spirosymplokos, are compared with all other spirochete genera. The large spirochete, grown in mixed culture, was studied live and by transmission EM. The protoplasmic cylinder was replete with spherical granules 20-32 nm in diameter, and three to six periplasmic 26-nm flagella were inserted subterminally. Comparably granulated and flagellated small spirochetes were located inside the protoplasmic cylinder and in the periplasm of the large ones. When exposed to air, movement became erratic, protoplasmic cylinders retracted to lie folded inside the outer membrane, and refractile membranous structures formed. From one to four structures per still-moving spirochete were seen. Spirosymplokos was enriched from laboratory samples exposed to oxygen-rich and desiccating, but not dry, conditions for at least 4 mo after removal of microbial mat from the field.

  6. Composite, large spirochetes from microbial mats: spirochete structure review.

    PubMed Central

    Margulis, L; Ashen, J B; Solé, M; Guerrero, R

    1993-01-01

    Phenomena previously unknown in free-living spirochetes are reported: large-sized cells with variable diameter (length to 100 microns, width between 0.4 and 3.0 microns), composite structure (smaller spirochetes inside larger ones), and positive phototropic behavior. These bacteria, Spirosymplokos, are compared with all other spirochete genera. The large spirochete, grown in mixed culture, was studied live and by transmission EM. The protoplasmic cylinder was replete with spherical granules 20-32 nm in diameter, and three to six periplasmic 26-nm flagella were inserted subterminally. Comparably granulated and flagellated small spirochetes were located inside the protoplasmic cylinder and in the periplasm of the large ones. When exposed to air, movement became erratic, protoplasmic cylinders retracted to lie folded inside the outer membrane, and refractile membranous structures formed. From one to four structures per still-moving spirochete were seen. Spirosymplokos was enriched from laboratory samples exposed to oxygen-rich and desiccating, but not dry, conditions for at least 4 mo after removal of microbial mat from the field. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8346204

  7. Infection of Ixodes ricinus (Acari: Ixodidae) by Borrelia burgdorferi sensu lato in North Africa

    USGS Publications Warehouse

    Zhioua, E.; Bouattour, A.; Hu, C.M.; Gharbi, M.; Aeschliman, A.; Ginsberg, H.S.; Gern, L.

    1999-01-01

    Free-living adult Ixodes ricinus L. were collected in Amdoun, situated in the Kroumiry mountains in northwestern Tunisia (North Africa). Using direct fluorescence antibody assay, the infection rate of field-collected I. ricinus by Borrelia burgdorferi sensu lato was 30.5% (n = 72). No difference in infection rate was observed between male and female ticks. Spirochetes that had been isolated from I. ricinus from Ain Drahim (Kroumiry Mountains) in 1988 were identified as Borrelia lusitaniae (formerly genospecies PotiB2). This is the first identification of a genospecies of Borrelia burgdorferi sensu lato from the continent of Africa.

  8. Persister Development by Borrelia burgdorferi Populations In Vitro

    PubMed Central

    Caskey, John R.

    2015-01-01

    Doxycycline is an antibiotic commonly used to treat Lyme disease and other bacterial infections. The MIC and minimum bactericidal concentration (MBC) for Borrelia burgdorferi have been investigated by different groups but were experimentally established in this study as a function of input cell density. We demonstrated that B. burgdorferi treated in the stationary phase has a higher probability of regrowth following removal of antibiotic. In addition, we determined experimentally and mathematically that the spirochetes which persist posttreatment do not have a longer lag phase but exhibit a lower growth rate than untreated spirochetes. Finally, we found that treating the spirochetes by pulse-dosing did not eliminate growth or reduce the persister population in vitro. From these data, we propose that B. burgdorferi persister development is stochastic and driven by slowed growth. PMID:26248368

  9. A tick gut protein with fibronectin III domains aids Borrelia burgdorferi congregation to the gut during transmission.

    PubMed

    Narasimhan, Sukanya; Coumou, Jeroen; Schuijt, Tim J; Boder, Eric; Hovius, Joppe W; Fikrig, Erol

    2014-08-01

    Borrelia burgdorferi transmission to the vertebrate host commences with growth of the spirochete in the tick gut and migration from the gut to the salivary glands. This complex process, involving intimate interactions of the spirochete with the gut epithelium, is pivotal to transmission. We utilized a yeast surface display library of tick gut proteins to perform a global screen for tick gut proteins that might interact with Borrelia membrane proteins. A putative fibronectin type III domain-containing tick gut protein (Ixofin3D) was most frequently identified from this screen and prioritized for further analysis. Immunization against Ixofin3D and RNA interference-mediated reduction in expression of Ixofin3D resulted in decreased spirochete burden in tick salivary glands and in the murine host. Microscopic examination showed decreased aggregation of spirochetes on the gut epithelium concomitant with reduced expression of Ixofin3D. Our observations suggest that the interaction between Borrelia and Ixofin3D facilitates spirochete congregation to the gut during transmission, and provides a "molecular exit" direction for spirochete egress from the gut.

  10. A Tick Gut Protein with Fibronectin III Domains Aids Borrelia burgdorferi Congregation to the Gut during Transmission

    PubMed Central

    Schuijt, Tim J.; Boder, Eric; Hovius, Joppe W.; Fikrig, Erol

    2014-01-01

    Borrelia burgdorferi transmission to the vertebrate host commences with growth of the spirochete in the tick gut and migration from the gut to the salivary glands. This complex process, involving intimate interactions of the spirochete with the gut epithelium, is pivotal to transmission. We utilized a yeast surface display library of tick gut proteins to perform a global screen for tick gut proteins that might interact with Borrelia membrane proteins. A putative fibronectin type III domain-containing tick gut protein (Ixofin3D) was most frequently identified from this screen and prioritized for further analysis. Immunization against Ixofin3D and RNA interference-mediated reduction in expression of Ixofin3D resulted in decreased spirochete burden in tick salivary glands and in the murine host. Microscopic examination showed decreased aggregation of spirochetes on the gut epithelium concomitant with reduced expression of Ixofin3D. Our observations suggest that the interaction between Borrelia and Ixofin3D facilitates spirochete congregation to the gut during transmission, and provides a “molecular exit” direction for spirochete egress from the gut. PMID:25102051

  11. Dynamics of connective-tissue localization during chronic Borrelia burgdorferi infection.

    PubMed

    Imai, Denise M; Feng, Sunlian; Hodzic, Emir; Barthold, Stephen W

    2013-08-01

    The etiologic agent of Lyme disease, Borrelia burgdorferi, localizes preferentially in the extracellular matrix during persistence. In chronically infected laboratory mice, there is a direct association between B. burgdorferi and the proteoglycan decorin, which suggests that decorin has a role in defining protective niches for persistent spirochetes. In this study, the tissue colocalization of B. burgdorferi with decorin and the dynamics of borrelial decorin tropism were evaluated during chronic infection. Spirochetes were found to colocalize absolutely with decorin, but not collagen I in chronically infected immunocompetent C3H mice. Passive immunization of infected C3H-scid mice with B. burgdorferi-specific immune serum resulted in the localization of spirochetes in decorin-rich microenvironments, with clearance of spirochetes from decorin-poor microenvironments. In passively immunized C3H-scid mice, tissue spirochete burdens were initially reduced, but increased over time as the B. burgdorferi-specific antibody levels waned. Concurrent repopulation of the previously cleared decorin-poor microenvironments was observed with the rising tissue spirochete burden and declining antibody titer. These findings indicate that the specificity of B. burgdorferi tissue localization during chronic infection is determined by decorin, driven by the borrelia-specific antibody response, and fluctuates with the antibody response. PMID:23797360

  12. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection

    PubMed Central

    Kwiatkowska, Ewa; Gołembiewska, Edyta; Ciechanowski, Kazimierz; Kędzierska, Karolina

    2012-01-01

    Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5–10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. (1997)). In available literature, there were reports of human's glomerulonephritis associated with Borrelia burgdorferi infection. These cases refer to membranous and mesangial proliferative glomerulonephritis (Kirmizis and Chatzidimitriou (2010), Zachäus (2008), and Kirmizis et al. (2004)). In this paper, we present the case of minimal-change disease (MCD) as a result of Borrelia burgdorferi infection. PMID:24527240

  13. Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi.

    PubMed

    Buffen, Kathrin; Oosting, Marije; Li, Yang; Kanneganti, Thirumala-Devi; Netea, Mihai G; Joosten, Leo A B

    2016-09-01

    We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regarding the effect of autophagy on in vivo models of Borrelia infection. Here, we showed that ATG7-deficient mice that were intra-articular injected with Borrelia spirochetes displayed increased joint swelling, cell influx, and enhanced interleukin-1β and interleukin-6 production by inflamed synovial tissue. Because both interleukin-1β and interleukin-6 are linked to the development of adaptive immune responses, we examine the function of autophagy on Borrelia induced adaptive immunity. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increase in interleukin-17, interleukin-22, and interferon-γ production in response to exposure to Borrelia burgdorferi. Increased IL-17 production was dependent on IL-1β release but, interestingly, not on interleukin-23 production. In addition, cytokine quantitative trait loci in ATG9B modulate the Borrelia induced interleukin-17 production. Because high levels of IL-17 have been found in patients with confirmed, severe, chronic borreliosis, we propose that the modulation of autophagy may be a potential target for anti-inflammatory therapy in patients with persistent Lyme disease. PMID:27101991

  14. Regulatory protein BBD18 of the lyme disease spirochete: essential role during tick acquisition?

    PubMed

    Hayes, Beth M; Dulebohn, Daniel P; Sarkar, Amit; Tilly, Kit; Bestor, Aaron; Ambroggio, Xavier; Rosa, Patricia A

    2014-04-01

    The Lyme disease spirochete Borrelia burgdorferi senses and responds to environmental cues as it transits between the tick vector and vertebrate host. Failure to properly adapt can block transmission of the spirochete and persistence in either vector or host. We previously identified BBD18, a novel plasmid-encoded protein of B. burgdorferi, as a putative repressor of the host-essential factor OspC. In this study, we investigate the in vivo role of BBD18 as a regulatory protein, using an experimental mouse-tick model system that closely resembles the natural infectious cycle of B. burgdorferi. We show that spirochetes that have been engineered to constitutively produce BBD18 can colonize and persist in ticks but do not infect mice when introduced by either tick bite or needle inoculation. Conversely, spirochetes lacking BBD18 can persistently infect mice but are not acquired by feeding ticks. Through site-directed mutagenesis, we have demonstrated that abrogation of spirochete infection in mice by overexpression of BBD18 occurs only with bbd18 alleles that can suppress OspC synthesis. Finally, we demonstrate that BBD18-mediated regulation does not utilize a previously described ospC operator sequence required by B. burgdorferi for persistence in immunocompetent mice. These data lead us to conclude that BBD18 does not represent the putative repressor utilized by B. burgdorferi for the specific downregulation of OspC in the mammalian host. Rather, we suggest that BBD18 exhibits features more consistent with those of a global regulatory protein whose critical role occurs during spirochete acquisition by feeding ticks. IMPORTANCE Lyme disease, caused by Borrelia burgdorferi, is the most common arthropod-borne disease in North America. B. burgdorferi is transmitted to humans and other vertebrate hosts by ticks as they take a blood meal. Transmission between vectors and hosts requires the bacterium to sense changes in the environment and adapt. However, the mechanisms

  15. Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: possible factors contributing to persistence of organisms.

    PubMed

    Nanagara, R; Duray, P H; Schumacher, H R

    1996-10-01

    To perform the first systematic electronmicroscopic (EM) and immunoelectron microscopy (IEM) study of the pathological changes and the evidence of spirochete presence in synovial membranes and synovial fluid (SF) cells of patients with chronic Lyme arthritis. EM examination was performed on four synovial membrane and eight SF cell samples from eight patients with chronic Lyme disease. Spirochetal antigens in the samples were sought by IEM using monoclonal antibody to Borrelia burgdorferi outer surface protein A (OspA) as the immunoprobe. Prominent ultrastructural findings were surface fibrin-like material, thickened synovial lining cell layer and signs of vascular injury. Borrelia-like structures were identified in all four synovial membranes and in two of eight SF cell samples. The presence of spirochetal antigens was confirmed by IEM in all four samples studied (one synovial membrane and three SF cell samples). OspA labelling was in perivascular areas, deep synovial stroma among collagen bundles, and in vacuoles of fibroblasts in synovial membranes; and in cytophagosomes of mononuclear cells in SF cell samples. Electron microscopy adds further evidence for persistence of spirochetal antigens in the joint in chronic Lyme disease. Locations of spirochetes or spirochetal antigens both intracellulary and extracellulary in deep synovial connective tissue as reported here suggest sites at which spirochaetes may elude host immune response and antibiotic treatment.

  16. Periplasmal Physics: The Rotational Dynamics of Spirochetal Flagella

    NASA Astrophysics Data System (ADS)

    Huber, Greg

    2012-02-01

    Spirochetes are distinguished by the location of their flagella, which reside within the periplasm: the tiny space between the bacterial cell wall and the outer membrane. In Borrelia burgdorferi/ (the causative agent of Lyme Disease), rotation of the flagella leads to cellular undulations that drive swimming. Exactly how these shape changes arise due to the forces and torques acting between the flagella and the cell body is unknown. By applying low-Reynolds number hydrodynamic theory to the motion of an elastic flagellum rotating in the periplasm, we show that the flagella are most likely separated from the bacterial cell wall by a lubricating layer of fluid. We obtain analytical solutions for the force and torque on the rotating flagellum through lubrication analysis, as well as through scaling analysis, and find results are in close agreement numerical simulations. (Joint work with J. Yang and C.W. Wolgemuth.)

  17. Tick-Borne Relapsing Fever Outbreak Among a High School Football Team at an Outdoor Education Camping Trip, Arizona, 2014.

    PubMed

    Jones, Jefferson M; Hranac, Carter R; Schumacher, Mare; Horn, Kim; Lee, Darlene M; Terriquez, Joel; Engelthaler, David M; Peoples, Marie; Corrigan, Jennifer; Replogle, Adam; Souders, Nina; Komatsu, Kenneth K; Nieto, Nathan C

    2016-09-01

    During August 2014, five high school students who had attended an outdoor education camp were hospitalized with a febrile illness, prompting further investigation. Ten total cases of tick-borne relapsing fever (TBRF) were identified-six cases confirmed by culture or visualization of spirochetes on blood smear and four probable cases with compatible symptoms (attack rate: 23%). All patients had slept in the campsite's only cabin. Before the camp, a professional pest control company had rodent proofed the cabin, but no acaricides had been applied. Cabin inspection after the camp found rodents and Ornithodoros ticks, the vector of TBRF. Blood samples from a chipmunk trapped near the cabin and from patients contained Borrelia hermsii with identical gene sequences (100% over 630 base pairs). Health departments in TBRF endemic areas should consider educating cabin owners and pest control companies to apply acaricides during or following rodent proofing, because ticks that lack rodents for a blood meal might feed on humans. PMID:27430539

  18. Borrelia hermsii Acquisition Order in Superinfected Ticks Determines Transmission Efficiency

    PubMed Central

    Raffel, Sandra J.; Schwan, Tom G.

    2013-01-01

    Multilocus sequence typing of Borrelia hermsii isolates reveals its divergence into two major genomic groups (GG), but no differences in transmission efficiency or host pathogenicity are associated with these genotypes. To compare GGI and GGII in the tick-host infection cycle, we first determined if spirochetes from the two groups could superinfect the tick vector Ornithodoros hermsi. We infected mice with isolates from each group and fed ticks sequentially on these mice. We then fed the infected ticks on naive mice and measured GGI and GGII spirochete densities in vector and host, using quantitative PCR of genotype-specific chromosomal DNA sequences. Sequential feedings resulted in dual tick infections, showing that GGI or GGII primary acquisition did not block superinfection by a secondary agent. On transmission to naive mice at short intervals after acquisition, ticks with primary GGI and secondary GGII spirochete infections caused mixed GGI and GGII infections in mice. However, ticks with primary GGII and secondary GGI spirochete infections caused only GGII infections with all isolate pairs examined. At longer intervals after acquisition, the exclusion of GGI by GGII spirochetes declined and cotransmission predominated. We then examined GGI and GGII spirochetemia in mice following single inoculation and coinoculation by needle and found that GGI spirochete densities were reduced on multiple days when coinoculated with GGII. These findings indicate that dual GGI-GGII spirochete infections can persist in ticks and that transmission to a vertebrate host is dependent on the order of tick acquisition and the interval between acquisition and transmission events. PMID:23716615

  19. Spatial stratification of various Lyme disease spirochetes in a Central European site.

    PubMed

    Richter, Dania; Schröder, Boris; Hartmann, Niklas K; Matuschka, Franz-Rainer

    2013-03-01

    To determine whether the genospecies composition of Lyme disease spirochetes is spatially stratified, we collected questing Ixodes ricinus ticks in neighboring plots where rodents, birds, and lizards were present as reservoir host and compared the prevalence of various genospecies. The overall prevalence of spirochetes in questing ticks varied across the study site. Borrelia lusitaniae appeared to infect adult ticks in one plot at the same frequency as did Borrelia afzelii in the other plots. The relative density of questing nymphal and adult ticks varied profoundly. Where lizards were exceedingly abundant, these vertebrates seemed to constitute the dominant host for nymphal ticks, contributing the majority of infected adult ticks. Because lizards support solely B. lusitaniae and appear to exclude other genospecies, their narrow genospecies association results in predominance of B. lusitaniae in sites where lizards are abundant, while limiting its spread to the host's habitat range. To the extent that Central European B. lusitaniae strains are nonpathogenic, the presence of numerous lizards should locally decrease risk of infection for people. Evaluation of regional risk of infection by Lyme disease spirochetes should take the spatial effect of hosts into consideration, which stratify the distribution of specifically infected ticks on a small scale.

  20. Spirochetemia caused by Borrelia turicatae infection in 3 dogs in Texas.

    PubMed

    Whitney, Marlyn S; Schwan, Tom G; Sultemeier, Katherine B; McDonald, Polly S; Brillhart, Martin N

    2007-06-01

    Spirochetemia was diagnosed in 2 Siberian Huskies and a Rottweiler from the northwestern region of Texas between June 1999 and October 2001. Clinical findings were nonspecific; tick exposure was documented in 2 of the dogs. Hematologic abnormalities included anemia (n=2), neutrophilia (n=2, including 1 with a left shift), lymphopenia (n=3), eosinopenia (n=3), and thrombocytopenia (n=2). One anemic dog had a positive Coombs' test. In 1 dog, Western blot analysis of serum yielded multiple positive bands with B turicatae lysate, indicating the spirochetemia most likely was due to B turicatae infection. In 2 dogs, spirochetes were cultured from the blood and identified using DNA analysis as Borrelia turicatae; 1 of these dogs also was seropositive for Ehrlichia canis and B burgdorferi. In 2 cases, spirochetemia was more prominent in blood smears prepared immediately after sample collection than in smears prepared from EDTA blood. Two dogs recovered with doxycycline treatment; 1 dog declined clinically despite treatment and was euthanized. B turicatae is the agent of tick-borne (endemic) relapsing fever in humans and is distinct from B burgdorferi, the agent of Lyme disease; however, serologic cross-reactivity may occur. B turicatae is transmitted by the soft tick, Ornithodoros turicata, and infection should be considered in dogs with spirochetemia and possible exposure to the tick vector.

  1. Community ecology and disease risk: lizards, squirrels, and the Lyme disease spirochete in California, USA.

    PubMed

    Salkeld, Daniel J; Lane, Robert S

    2010-01-01

    Vector-borne zoonotic diseases are often maintained in complex transmission cycles involving multiple vertebrate hosts and their arthropod vectors. In the state of California, U.S.A., the spirochete Borrelia burgdorferi, which causes Lyme disease, is transmitted between vertebrate hosts by the western black-legged tick, Ixodes pacificus. Several mammalian species serve as reservoir hosts of the spirochete, but levels of tick infestation, reservoir competence, and Borrelia-infection prevalence vary widely among such hosts. Here, we model the host (lizards, Peromyscus mice, Californian meadow voles, dusky-footed wood rats, and western gray squirrels), vector, and pathogen community of oak woodlands in northwestern California to determine the relative importance of different tick hosts. Observed infection prevalence of B. burgdorferi in host-seeking I. pacificus nymphs was 1.8-5.3%, and our host-community model estimated an infection prevalence of 1.6-2.2%. The western gray squirrel (Sciurus griseus) was the only source of infected nymphs. Lizards, which are refractory to Borrelia infection, are important in feeding subadult ticks but reduce disease risk (nymphal infection prevalence). Species identity is therefore critical in understanding and determining the local disease ecology. PMID:20380218

  2. Louse-borne relapsing fever (Borrelia recurrentis) diagnosed in 15 refugees from northeast Africa: epidemiology and preventive control measures, Bavaria, Germany, July to October 2015.

    PubMed

    Hoch, Martin; Wieser, Andreas; Löscher, Thomas; Margos, Gabriele; Pürner, Friedrich; Zühl, Jürgen; Seilmaier, Michael; Balzer, Lukas; Guggemos, Wolfgang; Rack-Hoch, Anita; von Both, Ulrich; Hauptvogel, Katja; Schönberger, Katharina; Hautmann, Wolfgang; Sing, Andreas; Fingerle, Volker

    2015-01-01

    We report 15 imported louse-borne relapsing fever (LBRF) cases in refugees in Bavaria, Germany. One patient died. Epidemiological findings confirmed that all were young males from the Horn of Africa (12 from Somalia), who had similar migration routes converging in Sudan continuing through Libya and Italy. The majority likely acquired their infection during migration. Healthcare workers should be aware of LBRF in refugees passing through north Africa to ensure correct treatment and preventive measures. PMID:26538532

  3. Louse-borne relapsing fever (Borrelia recurrentis) diagnosed in 15 refugees from northeast Africa: epidemiology and preventive control measures, Bavaria, Germany, July to October 2015.

    PubMed

    Hoch, Martin; Wieser, Andreas; Löscher, Thomas; Margos, Gabriele; Pürner, Friedrich; Zühl, Jürgen; Seilmaier, Michael; Balzer, Lukas; Guggemos, Wolfgang; Rack-Hoch, Anita; von Both, Ulrich; Hauptvogel, Katja; Schönberger, Katharina; Hautmann, Wolfgang; Sing, Andreas; Fingerle, Volker

    2015-01-01

    We report 15 imported louse-borne relapsing fever (LBRF) cases in refugees in Bavaria, Germany. One patient died. Epidemiological findings confirmed that all were young males from the Horn of Africa (12 from Somalia), who had similar migration routes converging in Sudan continuing through Libya and Italy. The majority likely acquired their infection during migration. Healthcare workers should be aware of LBRF in refugees passing through north Africa to ensure correct treatment and preventive measures.

  4. [Louse-borne-relapsing-fever in refugees from the Horn of Africa; a case series of 25 patients].

    PubMed

    Seilmaier, M; Guggemos, W; Wieser, A; Fingerle, V; Balzer, L; Fenzl, T; Hoch, M; von Both, U; Schmidt, H U; Wendtner, C M; Strobel, E

    2016-07-01

    Background | Relapsing fever is divided into tick borne relapsing fever (TBRF) and louse borne relapsing fever (LBRF). This report describes 25 refugees from East Africa who were diagnosed to suffer from LBRF within a period of 6 month only at a single hospital in Munich / Germany. Material & Methods | The aim was to point out common clinical features as well as laboratory findings and clinical symptoms before and after initiation of treatment in 25 patients with louse borne relapsing fever (LBRF) who were diagnosed and treated at Klinikum München Schwabing from August 2015 to January 2016. To the best of our knowledge this is the largest case series of LBRF in the western world for decades. Main focus of the investigation was put on clinical aspects. Results | All 25 patients suffered from acute onset of high fever with chills, headache and severe prostration. Laboratory analysis showed high CRP and a marked thrombocytopenia. A Giemsa blood stain was procured immediately in order to look for malaria. In the blood smear spirochetes with typical shape and aspect of borrelia species could be detected.The further PCR analysis confirmed infection with Borrelia recurrentis. Treatment with Doxycycline was started forthwith. The condition improved already on the second day after treatment was started and all were restored to health in less than a week. Apart from a mild to moderate Jarisch-Herxheimer-reaction we didn`t see any side effects of the therapy. Conclusion | LBRF has to be taken into account in feverish patients who come as refugees from East-Africa. It seems that our patients belong to a cluster which probably has its origin in Libya and more patients are to be expected in the near future. As LBRF might cause outbreaks in refugee camps it is pivotal to be aware of this emerging infectious disease in refugees from East-Africa. PMID:27404939

  5. Fourier transform infrared spectroscopy of DNA from Borrelia burgdorferi sensu lato and Ixodes ricinus ticks

    NASA Astrophysics Data System (ADS)

    Muntean, Cristina M.; Stefan, Razvan; Bindea, Maria; Cozma, Vasile

    2013-06-01

    In this work we present a method for detection of motile and immotile Borrelia burgdorferi genomic DNA, in relation with infectious and noninfectious spirochetes. An FT-IR study of DNA isolated from B. burgdorferi sensu lato strains and from positive and negative Ixodes ricinus ticks, respectively, is reported. Motile bacterial cells from the species B. burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii were of interest. Also, FT-IR absorbance spectra of DNA from immotile spirochetes of B. burgdorferi sensu stricto, in the absence and presence of different antibiotics (doxycycline, erythromycin, gentamicin, penicillin V or phenoxymethylpenicillin, tetracycline, respectively) were investigated. FT-IR spectra, providing a high molecular structural information, have been analyzed in the wavenumber range 400-1800 cm-1. FT-IR signatures, spectroscopic band assignments and structural interpretations of these DNAs are reported. Spectral differences between FT-IR absorbances of DNAs from motile bacterial cells and immotile spirochetes, respectively, have been found. Particularly, alterations of the sugar-phosphate B-form chain in the case of DNA from Borrelia immotile cells, as compared with DNA from B. burgdorferi sensu lato motile cells have been observed. Based on this work, specific B. burgdorferi sensu lato and I. ricinus DNA-ligand interactions, respectively, might be further investigated using Fourier transform infrared spectroscopy.

  6. An investigation of binding ability of Ixodes persulcatus Schulze Salp15 with Lyme disease spirochetes.

    PubMed

    Murase, Yusuke; Konnai, Satoru; Yamada, Shinji; Githaka, Naftaly; Isezaki, Masayoshi; Ito, Takuya; Takano, Ai; Ando, Shuji; Kawabata, Hiroki; Murata, Siro; Ohashi, Kazuhko

    2015-05-01

    Salp15, a 15-kDa tick salivary gland protein, has several suppressive modes of activity against host immunity and plays a critical role in the transmission of Lyme disease spirochetes in Ixodes scapularis and Ixodes ricinus, major vectors of Lyme disease in North America and Western Europe. Salp15 adheres to Borrelia burgdorferi and specifically interacts with its outer surface protein C (OspC), protecting the spirochete from antibody-mediated cytotoxicity and facilitating infection in the mice. Recently, we identified two Salp15 homologues, IperSalp15-1 and IperSalp15-2, in Ixodes persulcatus, a vector for Lyme disease in Japan. Here we describe the function of IperSalp15 in the transmission of Lyme borreliosis. To investigate the function of IperSalp15, recombinant IperSalp15-1 and IperSalp15-2 were prepared in bacterial and insect cells. Both were identified in the sera of tick-immunized hamsters, indicating that these are secretory proteins in exposed host animals. Solid-phase overlay and indirect fluorescence assays showed that IperSalp15 binds to OspC from B. burgdorferi, Borrelia garinii, and Borrelia afzelii. Importantly, this binding likely protected the spirochete from antibody-mediated cytotoxicity in vitro. In addition, IperSalp15 tended to facilitate infection in mice. Thus, further characterization of tick molecules, including IperSalp15, could lead to the development of new strategies to prevent the transmission of tick-borne diseases.

  7. Laboratory Cultivation and Maintenance of Borrelia miyamotoi.

    PubMed

    Stone, Brandee L; Brissette, Catherine A

    2016-01-01

    Borrelia miyamotoi is a relapsing fever tick-borne pathogen found in Ixodes spp. (hard) ticks. In vitro culturing has proven difficult despite initial reports of cultures maintained in Barbour-Stoenner-Kelly-II (BSK-II) medium. The ability to culture in vitro opens many avenues for investigating the genetics and physiology of bacterial species. This unit describes methods for the maintenance and cultivation of B. miyamotoi in liquid medium. © 2016 by John Wiley & Sons, Inc. PMID:27517334

  8. Reviewing molecular adaptations of Lyme borreliosis spirochetes in the context of reproductive fitness in natural transmission cycles.

    PubMed

    Tsao, Jean I

    2009-01-01

    Lyme borreliosis (LB) is caused by a group of pathogenic spirochetes - most often Borrelia burgdorferi, B. afzelii, and B. garinii - that are vectored by hard ticks in the Ixodes ricinus-persulcatus complex, which feed on a variety of mammals, birds, and lizards. Although LB is one of the best-studied vector-borne zoonoses, the annual incidence in North America and Europe leads other vector-borne diseases and continues to increase. What factors make the LB system so successful, and how can researchers hope to reduce disease risk - either through vaccinating humans or reducing the risk of contacting infected ticks in nature? Discoveries of molecular interactions involved in the transmission of LB spirochetes have accelerated recently, revealing complex interactions among the spirochete-tick-vertebrate triad. These interactions involve multiple, and often redundant, pathways that reflect the evolution of general and specific mechanisms by which the spirochetes survive and reproduce. Previous reviews have focused on the molecular interactions or population biology of the system. Here molecular interactions among the LB spirochete, its vector, and vertebrate hosts are reviewed in the context of natural maintenance cycles, which represent the ecological and evolutionary contexts that shape these interactions. This holistic system approach may help researchers develop additional testable hypotheses about transmission processes, interpret laboratory results, and guide development of future LB control measures and management. PMID:19368764

  9. Reviewing molecular adaptations of Lyme borreliosis spirochetes in the context of reproductive fitness in natural transmission cycles

    PubMed Central

    Tsao, Jean I.

    2009-01-01

    Lyme borreliosis (LB) is caused by a group of pathogenic spirochetes – most often Borrelia burgdorferi, B. afzelii, and B. garinii – that are vectored by hard ticks in the Ixodes ricinus-persulcatus complex, which feed on a variety of mammals, birds, and lizards. Although LB is one of the best-studied vector-borne zoonoses, the annual incidence in North America and Europe leads other vector-borne diseases and continues to increase. What factors make the LB system so successful, and how can researchers hope to reduce disease risk – either through vaccinating humans or reducing the risk of contacting infected ticks in nature? Discoveries of molecular interactions involved in the transmission of LB spirochetes have accelerated recently, revealing complex interactions among the spirochete-tick-vertebrate triad. These interactions involve multiple, and often redundant, pathways that reflect the evolution of general and specific mechanisms by which the spirochetes survive and reproduce. Previous reviews have focused on the molecular interactions or population biology of the system. Here molecular interactions among the LB spirochete, its vector, and vertebrate hosts are reviewed in the context of natural maintenance cycles, which represent the ecological and evolutionary contexts that shape these interactions. This holistic system approach may help researchers develop additional testable hypotheses about transmission processes, interpret laboratory results, and guide development of future LB control measures and management. PMID:19368764

  10. Nanoscopic Localization of Surface-Exposed Antigens of Borrelia burgdorferi.

    PubMed

    Lemgruber, Leandro; Sant'Anna, Celso; Griffths, Caron; Abud, Yuri; Mhlanga, Musa; Wallich, Reinhard; Frischknecht, Friedrich

    2015-06-01

    Borrelia burgdorferi sensu lato, the causative agent of Lyme disease, is transmitted to humans through the bite of infected Ixodes spp. ticks. Successful infection of vertebrate hosts necessitates sophisticated means of the pathogen to escape the vertebrates' immune system. One strategy employed by Lyme disease spirochetes to evade adaptive immunity involves a highly coordinated regulation of the expression of outer surface proteins that is vital for infection, dissemination, and persistence. Here we characterized the expression pattern of bacterial surface antigens using different microscopy techniques, from fluorescent wide field to super-resolution and immunogold-scanning electron microscopy. A fluorescent strain of B. burgdorferi spirochetes was labeled with monoclonal antibodies directed against various bacterial surface antigens. Our results indicate that OspA is more evenly distributed over the surface than OspB and OspC that were present as punctate areas. PMID:25739645

  11. Biomechanics of Borrelia burgdorferi Vascular Interactions.

    PubMed

    Ebady, Rhodaba; Niddam, Alexandra F; Boczula, Anna E; Kim, Yae Ram; Gupta, Nupur; Tang, Tian Tian; Odisho, Tanya; Zhi, Hui; Simmons, Craig A; Skare, Jon T; Moriarty, Tara J

    2016-09-01

    Systemic dissemination of microbes is critical for progression of many infectious diseases and is associated with most mortality due to bacterial infection. The physical mechanisms mediating a key dissemination step, bacterial association with vascular endothelia in blood vessels, remain unknown. Here, we show that endothelial interactions of the Lyme disease spirochete Borrelia burgdorferi under physiological shear stress mechanistically resemble selectin-dependent leukocyte rolling. Specifically, these interactions are mediated by transfer of mechanical load along a series of adhesion complexes and are stabilized by tethers and catch bond properties of the bacterial adhesin BBK32. Furthermore, we found that the forces imposed on adhesive bonds under flow may be small enough to permit active migration driven by bacterial flagellar motors. These findings provide insight into the biomechanics of bacterial-vascular interactions and demonstrate that disseminating bacteria and circulating host immune cells share widely conserved mechanisms for interacting with endothelia under physiological shear stress. PMID:27568563

  12. Borrelia recurrentis Employs a Novel Multifunctional Surface Protein with Anti-Complement, Anti-Opsonic and Invasive Potential to Escape Innate Immunity

    PubMed Central

    Grosskinsky, Sonja; Schott, Melanie; Brenner, Christiane; Cutler, Sally J.; Kraiczy, Peter; Zipfel, Peter F.; Simon, Markus M.; Wallich, Reinhard

    2009-01-01

    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 retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever. PMID:19308255

  13. Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

    PubMed Central

    Dunham-Ems, Star M.; Caimano, Melissa J.; Pal, Utpal; Wolgemuth, Charles W.; Eggers, Christian H.; Balic, Anamaria; Radolf, Justin D.

    2009-01-01

    Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination “adherence-mediated migration” and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease–causing spirochetes within ticks is exclusively motility driven. PMID:19920352

  14. What ticks do under your skin: two-photon intravital imaging of Ixodes scapularis feeding in the presence of the lyme disease spirochete.

    PubMed

    Bockenstedt, Linda K; Gonzalez, David; Mao, Jialing; Li, Ming; Belperron, Alexia A; Haberman, Ann

    2014-03-01

    Lyme disease, due to infection with the Ixodes-tick transmitted spirochete Borrelia burgdorferi, is the most common tick-transmitted disease in the northern hemisphere. Our understanding of the tick-pathogen-vertebrate host interactions that sustain an enzootic cycle for B. burgdorferi is incomplete. In this article, we describe a method for imaging the feeding of Ixodes scapularis nymphs in real-time using two-photon intravital microscopy and show how this technology can be applied to view the response of Lyme borrelia in the skin of an infected host to tick feeding.

  15. What Ticks Do Under Your Skin: Two-Photon Intravital Imaging of Ixodes Scapularis Feeding in the Presence of the Lyme Disease Spirochete

    PubMed Central

    Bockenstedt, Linda K.; Gonzalez, David; Mao, Jialing; Li, Ming; Belperron, Alexia A.; Haberman, Ann

    2014-01-01

    Lyme disease, due to infection with the Ixodes-tick transmitted spirochete Borrelia burgdorferi, is the most common tick-transmitted disease in the northern hemisphere. Our understanding of the tick-pathogen-vertebrate host interactions that sustain an enzootic cycle for B. burgdorferi is incomplete. In this article, we describe a method for imaging the feeding of Ixodes scapularis nymphs in real-time using two-photon intravital microscopy and show how this technology can be applied to view the response of Lyme borrelia in the skin of an infected host to tick feeding. PMID:24600332

  16. Collections of adult Ixodes dammini in Indiana, 1987-1990, and the isolation of Borrelia burgdorferi.

    PubMed

    Pinger, R R; Holycross, J; Ryder, J; Mummert, M

    1991-09-01

    The collection records for Ixodes dammini Spielman, Clifford, Piesman & Corwin in Indiana are summarized for the period 1987-1990. In 1990, 13 of 729 deer examined were found to harbor adult I. dammini ticks. Eleven of these ticks were collected from 10 deer at a site in Newton County in northwestern Indiana. Borrelia burgdorferi spirochetes were isolated from a single female I. dammini tick collected from this site.

  17. Differential tick burdens may explain differential Borrelia afzelii and Borrelia garinii infection rates among four, wild, rodent species in Hokkaido, Japan.

    PubMed

    Taylor, Kyle R; Takano, Ai; Konnai, Satoru; Shimozuru, Michito; Kawabata, Hiroki; Tsubota, Toshio

    2013-01-01

    The ecologies of Lyme disease Borrelia spp. are very specific to location, as they are dependent upon the spirochete species and genotypes, the vectors and the host vertebrates present. In Hokkaido, Japan, where two human pathogenic, Lyme disease Borrelia spp. are present, and human cases are reported annually, the ecologies have been poorly studied. Our goal was to determine whether variation in borrelial infection rates among rodent species sharing an environment, is due to immunological or ecological differences. To this end, we examined the relationships between tick burden and borrelial infection, by including examination of agreement between nested PCR, as a test for infection, and serology, as a test for exposure. We collected 868 rodents, comprised of four species commonly found in Hokkaido, and tested for infection rates with Borrelia spp. using PCR for the borrelial flaB gene, seroprevalence of Borrelia afzelii and Borrelia garinii using ELISA, and attachment of ticks by direct counts. We noted a correlation between differential nymph and larval burdens and the borrelial infection rates found among the four rodent species. Furthermore, there was significant correlation between infection and seroprevalence of B. afzelii and B. garinii (P<0.01), between infection and Ixodes persulcatus nymph burden (P<0.01), and between seroprevalence and I. persulcatus nymph burden (P<0.01). The close agreement among rodent species seroprevalences with infection rates and tick burdens suggest the differences in infection rates of Borrelia spp. may largely be a direct consequence of differential exposure to vectors.

  18. Antigenically variable Borrelia burgdorferi isolated from cottontail rabbits and Ixodes dentatus in rural and urban areas.

    PubMed Central

    Anderson, J F; Magnarelli, L A; LeFebvre, R B; Andreadis, T G; McAninch, J B; Perng, G C; Johnson, R C

    1989-01-01

    Spirochetes were isolated from 71 subadult Ixodes dentatus removed from cottontail rabbits captured in Millbrook, N.Y., and in New York, N.Y. Spirochetes were also cultured from kidney tissues of six rabbits. While all isolates reacted with monoclonal antibody H9724, which identifies the spirochetes as borreliae, more than half did not bind with antibody H5332 and even fewer reacted with H3TS, both of which were produced to outer surface protein A of Borrelia burgdorferi. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles of three isolates differed from one another and from all previously characterized B. burgdorferi strains from humans, ticks, and wildlife in North America. The 12 periplasmic flagella that originated subterminally from each pointed end of a rabbit Borellia isolate contrasted with the 11 or fewer flagella for B. burgdorferi reported previously from North America. Although DNA homology and restriction endonuclease analysis also revealed differences among a rabbit kidney isolate, an I. dentatus isolate, and B. burgdorferi B31, similarities were sufficient to lead us to conclude that the borreliae in rabbits and I. dentatus are B. burgdorferi. Enzyme-linked immunosorbent assay titers of sera from humans with diagnosed Lyme disease to rabbit tick B. burgdorferi were often similar to one another and to those recorded for a reference B. burgdorferi strain. Images PMID:2913024

  19. CD4+ cell-derived interleukin-17 in a model of dysregulated, Borrelia-induced arthritis.

    PubMed

    Hansen, Emily S; Johnson, Megan E; Schell, Ronald F; Nardelli, Dean T

    2016-10-01

    Lyme borreliosis, which is caused in the United States by the spirochete Borrelia burgdorferi, may manifest as different arrays of signs, symptoms and severities between infected individuals. Recent studies have indicated that particularly severe forms of Lyme borreliosis in humans are associated with an increased Th17 response. Here, we hypothesized that a murine model combining the dysregulated immune response of an environment lacking interleukin-10 (IL-10) with a robust T-cell-driven inflammatory response would reflect arthritis associated with the production of IL-17 by CD4+ cells. We demonstrate that IL-10 regulates the production of IL-17 by Borrelia-primed CD4+ cells early after interaction with Lyme spirochetes in vitro and that infection of Borrelia-primed mice with B. burgdorferi leads to significant production of IL-17 that contributes to the development of severe arthritis. These results extend our previous findings by demonstrating that a dysregulated adaptive immune response to Lyme spirochetes can contribute to severe, Th17-associated arthritis. These findings may lead to therapeutic measures for individuals with particularly severe symptoms of Lyme borreliosis. PMID:27549424

  20. Insights into the biology of Borrelia burgdorferi gained through the application of molecular genetics.

    PubMed

    Groshong, Ashley M; Blevins, Jon S

    2014-01-01

    Borrelia burgdorferi, the vector-borne bacterium that causes Lyme disease, was first identified in 1982. It is known that much of the pathology associated with Lyme borreliosis is due to the spirochete's ability to infect, colonize, disseminate, and survive within the vertebrate host. Early studies aimed at defining the biological contributions of individual genes during infection and transmission were hindered by the lack of adequate tools and techniques for molecular genetic analysis of the spirochete. The development of genetic manipulation techniques, paired with elucidation and annotation of the B. burgdorferi genome sequence, has led to major advancements in our understanding of the virulence factors and the molecular events associated with Lyme disease. Since the dawn of this genetic era of Lyme research, genes required for vector or host adaptation have garnered significant attention and highlighted the central role that these components play in the enzootic cycle of this pathogen. This chapter covers the progress made in the Borrelia field since the application of mutagenesis techniques and how they have allowed researchers to begin ascribing roles to individual genes. Understanding the complex process of adaptation and survival as the spirochete cycles between the tick vector and vertebrate host will lead to the development of more effective diagnostic tools as well as identification of novel therapeutic and vaccine targets. In this chapter, the Borrelia genes are presented in the context of their general biological roles in global gene regulation, motility, cell processes, immune evasion, and colonization/dissemination.

  1. Bgp, a secreted glycosaminoglycan-binding protein of Borrelia burgdorferi strain N40, displays nucleosidase activity and is not essential for infection of immunodeficient mice.

    PubMed

    Parveen, Nikhat; Cornell, Kenneth A; Bono, James L; Chamberland, Christen; Rosa, Patricia; Leong, John M

    2006-05-01

    Bgp, one of the surface-localized glycosaminoglycan-binding proteins of the Lyme disease spirochete, Borrelia burgdorferi, exhibited nucleosidase activity. Infection of SCID mice with B. burgdorferi strain N40 mutants harboring a targeted insertion in bgp and apparently retaining all endogenous plasmids revealed that Bgp is not essential for colonization of immunocompromised mice.

  2. Molecular Dissection of a Borrelia burgdorferi In Vivo Essential Purine Transport System

    PubMed Central

    Jain, Sunny; Showman, Adrienne C.

    2015-01-01

    The Lyme disease spirochete Borrelia burgdorferi is dependent on purine salvage from the host environment for survival. The genes bbb22 and bbb23 encode purine permeases that are essential for B. burgdorferi mouse infectivity. We now demonstrate the unique contributions of each of these genes to purine transport and murine infection. The affinities of spirochetes carrying bbb22 alone for hypoxanthine and adenine were similar to those of spirochetes carrying both genes. Spirochetes carrying bbb22 alone were able to achieve wild-type levels of adenine saturation but not hypoxanthine saturation, suggesting that maximal hypoxanthine uptake requires the presence of bbb23. Moreover, the purine transport activity conferred by bbb22 was dependent on an additional distal transcriptional start site located within the bbb23 open reading frame. The initial rates of uptake of hypoxanthine and adenine by spirochetes carrying bbb23 alone were below the level of detection. However, these spirochetes demonstrated a measurable increase in hypoxanthine uptake over a 30-min time course. Our findings indicate that bbb22-dependent adenine transport is essential for B. burgdorferi survival in mice. The bbb23 gene was dispensable for B. burgdorferi mouse infectivity, yet its presence was required along with that of bbb22 for B. burgdorferi to achieve maximal spirochete loads in infected mouse tissues. These data demonstrate that both genes, bbb22 and bbb23, are critical for B. burgdorferi to achieve wild-type infection of mice and that the differences in the capabilities of the two transporters may reflect distinct purine salvage needs that the spirochete encounters throughout its natural infectious cycle. PMID:25776752

  3. OspC-Independent Infection and Dissemination by Host-Adapted Borrelia burgdorferi▿

    PubMed Central

    Tilly, Kit; Bestor, Aaron; Dulebohn, Daniel P.; Rosa, Patricia A.

    2009-01-01

    Borrelia burgdorferi OspC is required for the spirochete to establish infection in a mammal by tick transmission or needle inoculation. After a brief essential period, the protein no longer is required and the gene can be shut off. Using a system in which spirochetes contain only an unstable wild-type copy of the ospC gene, we can obtain mice persistently infected with bacteria lacking OspC. We implanted pieces of infected mouse skin subcutaneously in naïve mice, using donors carrying wild-type or ospC mutant spirochetes, and found that both could infect mice by this method, with similar numbers of wild-type or ospC mutant spirochetes disseminated throughout the tissues of recipient mice. Recipient mouse immune responses to tissue transfer-mediated infection with wild-type or ospC mutant spirochetes were similar. These experiments demonstrate that mammalian host-adapted spirochetes can infect and disseminate in mice in the absence of OspC, thereby circumventing this hallmark of tick-derived or in vitro-grown spirochetes. We propose a model in which OspC is one of a succession of functionally equivalent, essential proteins that are synthesized at different stages of mammalian infection. In this model, another protein uniquely present on host-adapted spirochetes performs the same essential function initially fulfilled by OspC. The strict temporal control of B. burgdorferi outer surface protein gene expression may reflect immunological constraints rather than distinct functions. PMID:19398538

  4. Strain-Specific Variation of the Decorin-Binding Adhesin DbpA Influences the Tissue Tropism of the Lyme Disease Spirochete

    PubMed Central

    Lin, Yi-Pin; Benoit, Vivian; Yang, Xiuli; Martínez-Herranz, Raúl; Pal, Utpal; Leong, John M.

    2014-01-01

    Lyme disease spirochetes demonstrate strain- and species-specific differences in tissue tropism. For example, the three major Lyme disease spirochete species, Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii, are each most commonly associated with overlapping but distinct spectra of clinical manifestations. Borrelia burgdorferi sensu stricto, the most common Lyme spirochete in the U.S., is closely associated with arthritis. The attachment of microbial pathogens to cells or to the extracellular matrix of target tissues may promote colonization and disease, and the Lyme disease spirochete encodes several surface proteins, including the decorin- and dermatan sulfate-binding adhesin DbpA, which vary among strains and have been postulated to contribute to strain-specific differences in tissue tropism. DbpA variants differ in their ability to bind to its host ligands and to cultured mammalian cells. To directly test whether variation in dbpA influences tissue tropism, we analyzed murine infection by isogenic B. burgdorferi strains that encode different dbpA alleles. Compared to dbpA alleles of B. afzelii strain VS461 or B. burgdorferi strain N40-D10/E9, dbpA of B. garinii strain PBr conferred the greatest decorin- and dermatan sulfate-binding activity, promoted the greatest colonization at the inoculation site and heart, and caused the most severe carditis. The dbpA of strain N40-D10/E9 conferred the weakest decorin- and GAG-binding activity, but the most robust joint colonization and was the only dbpA allele capable of conferring significant joint disease. Thus, dbpA mediates colonization and disease by the Lyme disease spirochete in an allele-dependent manner and may contribute to the etiology of distinct clinical manifestations associated with different Lyme disease strains. This study provides important support for the long-postulated model that strain-specific variations of Borrelia surface proteins influence tissue tropism. PMID:25079227

  5. Strain-specific variation of the decorin-binding adhesin DbpA influences the tissue tropism of the lyme disease spirochete.

    PubMed

    Lin, Yi-Pin; Benoit, Vivian; Yang, Xiuli; Martínez-Herranz, Raúl; Pal, Utpal; Leong, John M

    2014-07-01

    Lyme disease spirochetes demonstrate strain- and species-specific differences in tissue tropism. For example, the three major Lyme disease spirochete species, Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii, are each most commonly associated with overlapping but distinct spectra of clinical manifestations. Borrelia burgdorferi sensu stricto, the most common Lyme spirochete in the U.S., is closely associated with arthritis. The attachment of microbial pathogens to cells or to the extracellular matrix of target tissues may promote colonization and disease, and the Lyme disease spirochete encodes several surface proteins, including the decorin- and dermatan sulfate-binding adhesin DbpA, which vary among strains and have been postulated to contribute to strain-specific differences in tissue tropism. DbpA variants differ in their ability to bind to its host ligands and to cultured mammalian cells. To directly test whether variation in dbpA influences tissue tropism, we analyzed murine infection by isogenic B. burgdorferi strains that encode different dbpA alleles. Compared to dbpA alleles of B. afzelii strain VS461 or B. burgdorferi strain N40-D10/E9, dbpA of B. garinii strain PBr conferred the greatest decorin- and dermatan sulfate-binding activity, promoted the greatest colonization at the inoculation site and heart, and caused the most severe carditis. The dbpA of strain N40-D10/E9 conferred the weakest decorin- and GAG-binding activity, but the most robust joint colonization and was the only dbpA allele capable of conferring significant joint disease. Thus, dbpA mediates colonization and disease by the Lyme disease spirochete in an allele-dependent manner and may contribute to the etiology of distinct clinical manifestations associated with different Lyme disease strains. This study provides important support for the long-postulated model that strain-specific variations of Borrelia surface proteins influence tissue tropism.

  6. Symbiotic spirochetes in the termite hindgut: phylogenetic identification of ectosymbiotic spirochetes of oxymonad protists.

    PubMed

    Iida; Ohkuma; Ohtoko; Kudo

    2000-10-01

    Some species of protists inhabiting the hindgut of lower-termites have a large number of ectosymbiotic spirochetes on the cell surface. The phylogenetic positions of the ectosymbiotic spirochetes of three oxymonad protists, Dinenympha porteri in the gut of Reticulitermes speratus, and Pyrsonympha sp. and Dinenympha sp. in Hodotermopsis sjoestedti, were investigated without cultivation of these organisms. Protist fractions carefully collected with a micromanipulator were used as templates for the amplification of small subunit ribosomal RNA genes (SSU rDNA). The phylogenetic tree inferred from the nucleotide sequences of the SSU rDNA showed that they were affiliated with the Treponema cluster of spirochetes and they were divided into two clusters. One was grouped together with the spirochetal sequences reported previously from the gut of termites and the other was related to the Treponema bryantii subgroup of treponemes (denoted as termite Treponema clusters I and II, respectively). Whole-cell in situ hybridization using a fluorescent-labeled oligonucleotide probe specific for the group of sequences in cluster II identified most of the ectosymbiotic spirochetes of the oxymonad protists in the gut of R. speratus and H. sjoestedti. However, not all of the ectosymbiotic spirochetes could be detected by means of this cluster II group-specific probe and the population of ectosymbiotic spirochetes of cluster II was different among the oxymonad species. In the case of D. porteri, an oligonucleotide probe specific for one member of cluster II recognized a portion of the ectosymbiotic spirochetes of cluster II, and their population was also different depending on the cell-type of D. porteri in terms of the attachment of ectosymbiotic spirochetes. The results indicate that the spirochetes of cluster II and probably those of a part of cluster I can be assigned to ectosymbiotic species of oxymonad protists and that the population of ectosymbiotic spirochetes associated with a

  7. Loss of Lyme disease spirochetes from Ixodes ricinus ticks feeding on European blackbirds.

    PubMed

    Matuschka, F R; Spielman, A

    1992-03-01

    To determine whether blackbirds (Turdus merula), the most abundant and most abundantly tick-infested ecotonal bird of Central Europe, may contribute to the transmission of the Lyme disease spirochete (Borrelia burgdorferi), we compared the infectivity to ticks of naturally as well as experimentally infected blackbirds and rodents. European blackbirds experience intense exposure to Ixodes ricinus ticks and to the pathogens that they transmit. In nature, subadult I. ricinus ticks found feeding on these birds generally contain no spirochetes, although infection is universal in those found on black-striped mice (Apodemus agrarius). Those found on yellow-necked mice (A. flavicollis) are less frequently infected. Ticks lose infection in the course of feeding on blackbirds and fail to infect them. Subadult I. ricinus ticks readily feed on blackbirds, black-striped mice, and jirds (Meriones unguiculatus), but engorge less fully on the bird than on the rodents. Although birds may burden human health by establishing new infestations of I. ricinus ticks, our observations indicate that particular birds may benefit health by locally diminishing transmission of the Lyme disease spirochete.

  8. Experimental infection of Columbian black-tailed deer with the Lyme disease spirochete.

    PubMed

    Lane, R S; Berger, D M; Casher, L E; Burgdorfer, W

    1994-01-01

    The course of Borrelia burgdorferi-infection in Columbian black-tailed deer. (Odocoileus hemionus columbianus), its effect on the health of these animals, and their reservoir competence for fleas were evaluated experimentally. Four yearling females inoculated intramuscularly with 10(8) organisms of the CA4 strain of B. burgdorferi, and two yearling males unexposed to spirochetes, were monitored daily for 3 mo. Spirochetes were reisolated from the blood of three does at 14 or 70 days postinjection, and from several tissues of the fourth doe at necropsy. Considerable antigenic heterogeneity was observed among the reisolates as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Only two of the four infected deer developed significant antibodies (> or = 1:128) to B. burgdorferi with titers persisting for < or = 2 mo. Hematological values were highly variable and the degree of variation observed was much greater than that reported previously for Columbian black-tailed deer or other subspecies of mule deer. Infected deer did not manifest signs of Lyme disease. On histologic examination of eight tissues per deer, we observed a minimal hepatic lesion in all animals exposed to B. burgdorferi. No spirochetes were detected in 367 fleas (Pulex irritans) that had naturally infested these deer; thus this flea probably is an inefficient host of B. burgdorferi.

  9. Tick-borne relapsing fever: an interstate outbreak originating at Grand Canyon National Park.

    PubMed

    Boyer, K M; Munford, R S; Maupin, G O; Pattison, C P; Fox, M D; Barnes, A M; Jones, W L; Maynard, J E

    1977-05-01

    During the 1973 summer season, 27 employees and 35 overnight guests at the North Rim, Grand Canyon National Park, Arizona, acquired febrile illnesses compatibel with relapsing fever. Sixteen cases were confirmed by finding Borrelia spirochetes in peripheral blood smears or inoculated Swiss mice. Retrospective surveys of 278 employees and 7247 guests at the park revealed that acquisition of illness was significantly associated with the persons sleeping in rustic log cabins and acquiring bites of "unknown" insects. From rodent nesting materials found in the walls and attics of cabins where cases had occurred, infective Ornithodoros hermsi ticks were recovered. Exceptional activity of ticks in human populations appeared to have resulted from a decreased population of the ticks' usual rodent hosts. Vector control activities consisted of spraying the cabins with residual insecticide, removing nesting materials, and "rodent proofing." This outbreak, the largest yet identified in North America, extends the known range of a principal vector and establishes the North Rim as an endemic source of tick-borne relapsing fever.

  10. Borrelia burgdorferi Induces the Production and Release of Proinflammatory Cytokines in Canine Synovial Explant Cultures

    PubMed Central

    Straubinger, Reinhard K.; Straubinger, Alix F.; Summers, Brian A.; Erb, Hollis N.; Härter, Luc; Appel, Max J. G.

    1998-01-01

    Canine synovial membrane explants were exposed to high- or low-passage Borrelia burgdorferi for 3, 6, 12, and 24 h. Spirochetes received no treatment, were UV light irradiated for 16 h, or were sonicated prior to addition to synovial explant cultures. In explant tissues, mRNA levels for the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1α (IL-1α), IL-1β, and IL-8 were surveyed semiquantitatively by reverse transcription-PCR. Culture supernatants were examined for numbers of total and motile (i.e., viable) spirochetes, TNF-like and IL-1-like activities, polymorphonuclear neutrophil (PMN) chemotaxis-inducing activities, and IL-8. During exposure to synovial explant tissues, the total number of spirochetes in the supernatants decreased gradually by ∼30%, and the viability also declined. mRNAs for TNF-α, IL-1α, IL-1β, and IL-8 were up-regulated in synovial explant tissues within 3 h after infection with untreated or UV light-irradiated B. burgdorferi, and mRNA levels corresponded to the results obtained with bioassays. During 24 h of coincubation, cultures challenged with untreated or UV light-irradiated spirochetes produced similar levels of TNF-like and IL-1-like activities. In contrast, explant tissues exposed to untreated B. burgdorferi generated significantly higher levels of chemotactic factors after 24 h of incubation than did explant tissues exposed to UV light-treated spirochetes. In identical samples, a specific signal for IL-8 was identified by Western blot analysis. High- and low-passage borreliae did not differ in their abilities to induce proinflammatory cytokines. No difference in cytokine induction between untreated and sonicated high-passage spirochetes was observed, suggesting that fractions of the organism can trigger the production and release of inflammatory mediators. The titration of spirochetes revealed a dose-independent cytokine response, where 103 to 107 B. burgdorferi organisms induced similar TNF

  11. Recovery of Lyme disease spirochetes from patients.

    PubMed Central

    Steere, A. C.; Grodzicki, R. L.; Craft, J. E.; Shrestha, M.; Kornblatt, A. N.; Malawista, S. E.

    1984-01-01

    Since the summer of 1982, we have cultured patient specimens for Lyme disease spirochetes. Of 118 patients cultured, four specimens yielded spirochetes: two from blood, one from a skin biopsy specimen of erythema chronicum migrans (ECM), and one from cerebrospinal fluid. All four isolates appeared identical when examined with a monoclonal antibody. However, attempts to recover the spirochete from synovium or synovial fluid were unsuccessful. In addition, the organism could not be visualized in skin or synovial biopsy specimens using the avidin-biotin peroxidase complex detection system. Thus, the current yield in culturing spirochetes from patients is quite low, and it is not yet known whether the organism is still alive later in the disease when arthritis is present. PMID:6393606

  12. In vitro activities of faropenem, ertapenem, imipenem and meropenem against Borrelia burgdorferi s.l.

    PubMed

    Rödel, Rebecca; Freyer, Alexandra; Bittner, Thomas; Schäfer, Volker; Hunfeld, Klaus-Peter

    2007-07-01

    Little is known about the in vitro activity of penems and carbapenems against the spirochete Borrelia burgdorferi. Here, faropenem, ertapenem, imipenem and meropenem as well as the third-generation cephalosporin ceftriaxone and tobramycin were tested in vitro against 11 isolates of the B. burgdorferi sensu lato complex. On a microg/mL basis, ertapenem was the most potent carbapenem (minimal inhibitory concentration (MIC) range: 0.015-0.125 microg/mL), with in vitro activity comparable with that of ceftriaxone against Borrelia. These findings are supported by the results of time-kill experiments in a Borrelia afzelii skin isolate, demonstrating a >3 log10 unit (99.9%) reduction of the inoculum after 96 h of exposure to either drug at a concentration of three log2 unit dilutions above the respective MIC. PMID:17512703

  13. The anti-borreliae efficacy of phytochemicals and micronutrients: an update

    PubMed Central

    Goc, Anna; Rath, Matthias

    2016-01-01

    Naturally occurring substances have been used for centuries to fight against various pathogens. They serve as a source for new chemical entities or provide options to already existing therapeutics. While there is an increasing interest in studying antimicrobial properties of naturally derived agents, little is known about their effects against Borrelia burgdorferi sensu lato, the causative pathogens of Lyme disease. A better understanding of this aspect could advance knowledge about pathophysiology of these bacteria and help improve the efficacy of current approaches against Lyme disease. Here, we review all naturally occurring substances scientifically evaluated to date, including plant extracts, their metabolites, and micronutrients, against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia sp. This summary reveals the potent anti-borreliae activity of several of these natural compounds indicating their potential in enhancing the efficacy of current treatments for Lyme disease, and offering new options to already existing therapeutic regiments. PMID:27536352

  14. The anti-borreliae efficacy of phytochemicals and micronutrients: an update.

    PubMed

    Goc, Anna; Rath, Matthias

    2016-06-01

    Naturally occurring substances have been used for centuries to fight against various pathogens. They serve as a source for new chemical entities or provide options to already existing therapeutics. While there is an increasing interest in studying antimicrobial properties of naturally derived agents, little is known about their effects against Borrelia burgdorferi sensu lato, the causative pathogens of Lyme disease. A better understanding of this aspect could advance knowledge about pathophysiology of these bacteria and help improve the efficacy of current approaches against Lyme disease. Here, we review all naturally occurring substances scientifically evaluated to date, including plant extracts, their metabolites, and micronutrients, against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia sp. This summary reveals the potent anti-borreliae activity of several of these natural compounds indicating their potential in enhancing the efficacy of current treatments for Lyme disease, and offering new options to already existing therapeutic regiments. PMID:27536352

  15. Borrelia Species in Host-Seeking Ticks and Small Mammals in Northern Florida

    PubMed Central

    Clark, Kerry

    2004-01-01

    The aim of this study was to improve understanding of several factors related to the ecology and environmental risk of Borrelia infection in northern Florida. Small mammals and host-seeking adult ticks were collected at several sites, and specimens were tested for the presence of Borrelia species, primarily by PCR amplification. Tissues from some vertebrates and ticks were initially cultured in BSK-H medium to isolate spirochetes, but none were recovered. However, comparison of partial flagellin (flaB), 66-kDa protein (p66), and outer surface protein A (ospA) gene sequences from DNAs amplified from small mammals and ticks confirmed the presence of several Borrelia species. Borrelia lonestari DNA was detected among lone star ticks (Amblyomma americanum) at four sites. Borrelia burgdorferi sensu stricto strains were detected in all small mammal species tested and in A. americanum, Ixodes affinis, and Ixodes scapularis ticks. Borrelia bissettii was found in a cotton mouse and cotton rats and in I. affinis ticks. The study findings extend the known geographic distributions of B. lonestari in A. americanum and of B. burgdorferi sensu lato in A. americanum, I. affinis, I. scapularis, and small mammals to new sites in Florida. The presence of B. burgdorferi sensu stricto strains in host-seeking lone star ticks at two sites in Florida suggests that A. americanum should still be considered a possible vector of B. burgdorferi sensu lato. PMID:15528699

  16. Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice.

    PubMed Central

    Bockenstedt, L K; Hodzic, E; Feng, S; Bourrel, K W; de Silva, A; Montgomery, R R; Fikrig, E; Radolf, J D; Barthold, S W

    1997-01-01

    Antibodies to the outer surface proteins (Osps) A, B, and C of the spirochete Borrelia burgdorferi can prevent infection in animal models of Lyme borreliosis. We have previously demonstrated that immune serum from mice infected with B. burgdorferi N40 can also prevent challenge infection and induce disease regression in infected mice. The antigens targeted by protective and disease-modulating antibodies are presently unknown, but they do not include Osp A or Osp B. Because Osp C antibodies are present in immune mouse serum, we investigated the ability of hyperimmune serum to recombinant Osp C (N40) to protect mice against challenge infection with N40 spirochetes. In both active and passive immunization studies, Osp C (N40) antiserum failed to protect mice from challenge infection with cultured organisms. Mice actively immunized with recombinant Osp C (N40) were susceptible to tick-borne challenge infection, and nymphal ticks remained infected after feeding on Osp C-hyperimmunized mice. In contrast, similar immunization studies performed with Osp C (PKo) antiserum prevented challenge infection of mice with a clone of PKo spirochetes pathogenic for mice. Both Osp C (N40) and Osp C (PKo) antisera showed minimal in vitro borreliacidal activity, and immunofluorescence studies localized Osp C beneath the outer membrane of both N40 and PKo spirochetes. We conclude that Osp C antibody-mediated immunity is strain specific and propose that differences in Osp C surface expression by spirochetes in vivo may account for strain-specific immunity. PMID:9353047

  17. [An experimental study of the capacity of the rat mite Ornithonyssus bacoti (Hirst, 1913) to ingest, maintain and transmit Borrelia].

    PubMed

    Lopatina, Iu V; Vasil'eva, I S; Gutova, V P; Ershova, A S; Burakova, O V; Naumov, R L; Petrova, A D

    1999-01-01

    For the first time a possibility of the gamasina mites' O. bacoti participation in Lyme disease spirochetes' circulation has been demonstrated. It has been experimentally shown that Borrelia burgdorferi s.l. are received by O. bacoti, survive in them for at least 21 days and are transmitted to white mice through mites' bites. Mice's infestation has occurred in 23% of cases. It is suggested that other bloodsucking gamasina mites inhabiting the Lyme borreliosis reservoir rodents nests may be capable of participating in borrelia circulation in the Lyme disease endemic areas. PMID:10703202

  18. Borrelia chilensis, a new member of the Borrelia burgdorferi sensu lato complex that extends the range of this genospecies in the Southern Hemisphere

    PubMed Central

    Ivanova, Larisa B.; Tomova, Alexandra; González-Acuña, Daniel; Murúa, Roberto; Moreno, Claudia X.; Hernández, Claudio; Cabello, Javier; Cabello, Carlos; Daniels, Thomas J.; Godfrey, Henry P.; Cabello, Felipe C.

    2014-01-01

    Summary Borrelia burgdorferi sensu lato (s.l.), transmitted by Ixodes spp. ticks, is the causative agent of Lyme disease. Although Ixodes spp. ticks are distributed in both Northern and Southern Hemispheres, evidence for the presence of B. burgdorferi s.l. in South America apart from Uruguay is lacking. We now report the presence of culturable spirochetes with flat-wave morphology and borrelial DNA in endemic Ixodes stilesi ticks collected in Chile from environmental vegetation and long-tailed rice rats (Oligoryzomys longicaudatus). Cultured spirochetes and borrelial DNA in ticks were characterized by multilocus sequence typing and by sequencing five other loci (16S and 23S ribosomal genes, 5S-23S intergenic spacer, flaB, ospC). Phylogenetic analysis placed this spirochete as a new genospecies within the Lyme borreliosis group. Its plasmid profile determined by PCR and pulsed-field gel electrophoresis differed from that of B. burgdorferi B31A3. We propose naming this new South American member of the Lyme borreliosis group Borrelia chilensis VA1, in honor of its country of origin. PMID:24148079

  19. Eco-epidemiological factors contributing to the low risk of human exposure to ixodid tick-borne borreliae in southern California, USA.

    PubMed

    Lane, Robert S; Fedorova, Natalia; Kleinjan, Joyce E; Maxwell, Matthew

    2013-09-01

    Little is known about the eco-epidemiology of Lyme disease in southern California, a region where the incidence is much lower than it is in northern California. Here, we sought to discover the previously unknown microhabitats of nymphs of the primary vector, the western black-legged tick (Ixodes pacificus), in 3 moderately to heavily-utilized state parks in the Santa Monica Mountains in Los Angeles County; to elucidate the seasonal distribution and abundance of adults of I. pacificus and another human-biter, the Pacific Coast tick (Dermacentor occidentalis); and to determine what Lyme-disease or relapsing-fever group borreliae are present in questing nymphs or adult ticks. I. pacificus nymphs were collected infrequently at various times of day in 2 chaparral or 7 woodland litter areas by dragging (combined mean=0.4 nymphs per hour). The western fence lizard (Sceloporus occidentalis) was a choice sentinel animal for detecting the presence of I. pacificus nymphs (and larvae) in diverse biotopes even when dragging litter in them was fruitless. The abundance and seasonality of I. pacificus and D. occidentalis adults resembled what had been documented previously for these ticks in northern California. Overall, zero of 27 free-living and 118 lizard-infesting I. pacificus nymphs, 7 (0.29%) of 2392 I. pacificus adults and 2 (0.22%) of 896 D. occidentalis adults were infected with Borrelia burgdorferi sensu lato (Bb sl), but none of them harbored B. miyamotoi, a relapsing-fever group spirochete implicated recently as a zoonotic pathogen in Russia. Borrelia americana and the human pathogen B. burgdorferi sensu stricto were each detected in one (0.04%), and uncharacterized Bb sl in 5 adult I. pacificus (0.21%) that clustered with B. americana. Both PCR-positive D. occidentalis adults contained B. burgdorferi sensu stricto. We conclude that the acarologic risk of being bitten by a B. burgdorferi sensu lato-infected ixodid tick in the habitats studied is slight, which offers a

  20. Eco-epidemiological factors contributing to the low risk of human exposure to ixodid tick-borne borreliae in southern California, USA.

    PubMed

    Lane, Robert S; Fedorova, Natalia; Kleinjan, Joyce E; Maxwell, Matthew

    2013-09-01

    Little is known about the eco-epidemiology of Lyme disease in southern California, a region where the incidence is much lower than it is in northern California. Here, we sought to discover the previously unknown microhabitats of nymphs of the primary vector, the western black-legged tick (Ixodes pacificus), in 3 moderately to heavily-utilized state parks in the Santa Monica Mountains in Los Angeles County; to elucidate the seasonal distribution and abundance of adults of I. pacificus and another human-biter, the Pacific Coast tick (Dermacentor occidentalis); and to determine what Lyme-disease or relapsing-fever group borreliae are present in questing nymphs or adult ticks. I. pacificus nymphs were collected infrequently at various times of day in 2 chaparral or 7 woodland litter areas by dragging (combined mean=0.4 nymphs per hour). The western fence lizard (Sceloporus occidentalis) was a choice sentinel animal for detecting the presence of I. pacificus nymphs (and larvae) in diverse biotopes even when dragging litter in them was fruitless. The abundance and seasonality of I. pacificus and D. occidentalis adults resembled what had been documented previously for these ticks in northern California. Overall, zero of 27 free-living and 118 lizard-infesting I. pacificus nymphs, 7 (0.29%) of 2392 I. pacificus adults and 2 (0.22%) of 896 D. occidentalis adults were infected with Borrelia burgdorferi sensu lato (Bb sl), but none of them harbored B. miyamotoi, a relapsing-fever group spirochete implicated recently as a zoonotic pathogen in Russia. Borrelia americana and the human pathogen B. burgdorferi sensu stricto were each detected in one (0.04%), and uncharacterized Bb sl in 5 adult I. pacificus (0.21%) that clustered with B. americana. Both PCR-positive D. occidentalis adults contained B. burgdorferi sensu stricto. We conclude that the acarologic risk of being bitten by a B. burgdorferi sensu lato-infected ixodid tick in the habitats studied is slight, which offers a

  1. Lyme Borreliosis: is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains?

    PubMed Central

    Hodzic, Emir

    2015-01-01

    The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes. PMID:26295288

  2. Borrelia garinii Induces CXCL13 Production in Human Monocytes through Toll-Like Receptor 2▿

    PubMed Central

    Rupprecht, Tobias A.; Kirschning, Carsten J.; Popp, Bernadette; Kastenbauer, Stefan; Fingerle, Volker; Pfister, Hans-Walter; Koedel, Uwe

    2007-01-01

    Recent studies have suggested an important role for the B-cell-attracting chemokine CXCL13 in the B-cell-dominated cerebrospinal fluid (CSF) infiltrate in patients with neuroborreliosis (NB). High levels of CXCL13 were present in the CSF of NB patients. It has not been clear, however, whether high CSF CXCL13 titers are specific for NB or are a characteristic of other spirochetal diseases as well. Furthermore, the mechanisms leading to the observed CXCL13 expression have not been identified yet. Here we describe similarly elevated CSF CXCL13 levels in patients with neurosyphilis, while pneumococcal meningitis patient CSF do not have high CXCL13 levels. In parallel, challenge of human monocytes in vitro with two of the spirochetal causative organisms, Borrelia garinii (the Borrelia species most frequently found in NB patients) and Treponema pallidum, but not challenge with pneumococci, induced CXCL13 release. This finding implies that a common spirochetal motif is a CXCL13 inducer. Accordingly, we found that the lipid moiety N-palmitoyl-S-(bis[palmitoyloxy]propyl)cystein (Pam3C) (three palmitoyl residues bound to N-terminal cysteine) of the spirochetal lipoproteins is critical for the CXCL13 induction in monocytes. As the Pam3C motif is known to signal via Toll-like receptor 2 (TLR2) and an anti-TLR2 monoclonal antibody blocked CXCL13 production of human monocytes incubated with B. garinii, this suggests that TLR2 is a major mediator of Borrelia-induced secretion of CXCL13 from human monocytes. PMID:17562761

  3. Borrelia burgdorferi in tick cell culture modulates expression of outer surface proteins A and C in response to temperature.

    PubMed

    Obonyo, M; Munderloh, U G; Fingerle, V; Wilske, B; Kurtti, T J

    1999-07-01

    The Lyme disease spirochete Borrelia burgdorferi sensu stricto downregulates outer surface protein A (OspA) and upregulates outer surface protein C (OspC) during tick feeding. The switching of these proteins correlates with increased spirochetal infectivity for the mammal. We examined the effect of temperature on differential expression of OspA and OspC by B. burgdorferi cocultivated with a cell line isolated from the vector tick Ixodes scapularis. The effect of incubation at 31, 34, or 37 degrees C on expression of OspA and OspC by B. burgdorferi JMNT and N40 was analyzed by indirect fluorescent-antibody microscopy, polyacrylamide gel electrophoresis, and immunoblotting. The amount of OspA relative to the amount of flagellin was highest in spirochetes cocultivated with tick cells at 31 degrees C and declined with increasing temperature in both strains. OspC production was enhanced in spirochetes cocultivated with tick cells at 37 degrees C. Spirochetes grown axenically in BSK-H medium also produced more OspC at 37 degrees C, but OspA content was not appreciably affected by temperature. Our findings indicate that temperature, along with cultivation in a tick cell culture system, plays a role in the differential expression of OspA and enhances differential expression of OspC by spirochetes.

  4. Extracellular secretion of the Borrelia burgdorferi Oms28 porin and Bgp, a glycosaminoglycan binding protein.

    PubMed

    Cluss, Robert G; Silverman, Damon A; Stafford, Thomas R

    2004-11-01

    Borrelia burgdorferi, the Lyme disease pathogen, cycles between its Ixodes tick vector and vertebrate hosts, adapting to vastly different biochemical environments. Spirochete gene expression as a function of temperature, pH, growth phase, and host milieu is well studied, and recent work suggests that regulatory networks are involved. Here, we examine the release of Borrelia burgdorferi strain B31 proteins into conditioned medium. Spirochetes intrinsically radiolabeled at concentrations ranging from 10(7) to 10(9) cells per ml secreted Oms28, a previously characterized outer membrane porin, into RPMI medium. As determined by immunoblotting, this secretion was not associated with outer membrane blebs or cytoplasmic contamination. A similar profile of secreted proteins was obtained for spirochetes radiolabeled in mixtures of RPMI medium and serum-free Barbour-Stoenner-Kelly (BSK II) medium. Proteomic liquid chromatography-tandem mass spectrometry analysis of tryptic fragments derived from strain B31 culture supernatants confirmed the identity of the 28-kDa species as Oms28 and revealed a 26-kDa protein as 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs-2), previously described as Bgp, a glycosaminoglycan-binding protein. The release of Oms28 into the culture medium is more selective when the spirochetes are in logarithmic phase of growth compared to organisms obtained from stationary phase. As determined by immunoblotting, stationary-phase spirochetes released OspA, OspB, and flagellin. Oms28 secreted by strains B31, HB19, and N40 was also recovered by radioimmunoprecipitation. This is the first report of B. burgdorferi protein secretion into the extracellular environment. The possible roles of Oms28 and Bgp in the host-pathogen interaction are considered.

  5. Systemic disease in Peromyscus leucopus associated with Borrelia burgdorferi infection.

    PubMed

    Burgess, E C; French, J B; Gendron-Fitzpatrick, A

    1990-03-01

    Sixteen wild Peromyscus leucopus, trapped for the establishment of a breeding colony, developed signs of neurological damage (trembling, incoordination, circling, head tilt, and lameness of the rear legs) 2-47 days after capture in southern Wisconsin. Spirochetes were cultured from the brain of 5/11 mice, and Borrelia burgdorferi was cultured from 1 brain. A spirochete was isolated from the bladder of 1 mouse. The spirochete was identified by fluorescent antibody staining with the monoclonal antibody specific for B. burgdorferi, H5332. Serum antibodies to the spirochete were found in 14/15 mice. Negative results were obtained in all tests for viruses and bacteria, including Listeria (2/2), Mycoplasma (2/2), mouse hepatitis virus (10/10), Theilers's encephalomyelitis virus (GD VII) (8/8), REO 3 virus (2/2), and lymphocytic choriomeningitis virus (4/4). There was no bacterial growth from brains cultured on eosin methylene blue or blood agar (3/3). Histologic lesions included nonsuppurative cellular infiltrates in the brain, kidney, liver, and lung. Three outbred Swiss-Webster mice were inoculated orally with a suspension of the brain in BSKII medium, and 3 were inoculated with unpassed B. burgdorferi cultured from the brain of a P. leucopus with motor dysfunction. Five of the inoculated mice developed antibody titers of 1:128; one mouse was positive at 1:256. Motor signs of neurologic damage developed in 3/6 mice 2-24 weeks post-inoculation, and B. burgdorferi was detected in the brains of 2 mice by isolation and by fluorescent antibody.

  6. Mode of inoculation of the Lyme disease agent Borrelia burgdorferi influences infection and immune responses in inbred strains of mice.

    PubMed

    Gern, L; Schaible, U E; Simon, M M

    1993-04-01

    Mice were infected with Borrelia burgdorferi by infection via Ixodes ricinus and experimental inoculation to determine whether transmission rates of spirochetes and antibody responses are influenced. Mice infected by the natural route were substantially more infective for ticks; two- to sixfold more tick larvae were positive for B. burgdorferi than those fed on experimentally inoculated mice. In natural infection, spirochetemia may be greater or spirochetes may be more accessible for transmission. Thus, this form of xenodiagnosis could be used to determine levels of spirochetes in the vertebrate host. Similar levels of antibody were present in all mice; however, those infected by the natural route lacked antibodies to outer surface proteins (Osp) A and B. The small antigen dose given through a tick bite may not have been sufficient to induce rapid OspA or OspB antibodies, thereby allowing the later development of higher levels of spirochetemia.

  7. Infection in rabbits with the Lyme disease spirochete.

    PubMed Central

    Kornblatt, A. N.; Steere, A. C.; Brownstein, D. G.

    1984-01-01

    Of 33 rabbits inoculated with Lyme disease spirochetes, two developed erythema chronicum migrans at the site of inoculation. Spirochetes were seen in skin biopsies of one of the lesions with immunoperoxidase and Warthin-Starry stains. Spirochetes were also recovered from the blood of two additional rabbits two weeks post-inoculation. These findings are characteristic of early Lyme disease in humans. PMID:6393613

  8. Fluorescent membrane markers elucidate the association of Borrelia burgdorferi with tick cell lines

    PubMed Central

    Teixeira, R.C.; Baêta, B.A.; Ferreira, J.S.; Medeiros, R.C.; Maya-Monteiro, C.M.; Lara, F.A.; Bell-Sakyi, L.; Fonseca, A.H.

    2016-01-01

    This study aimed to describe the association of Borrelia burgdorferi s.s. with ixodid tick cell lines by flow cytometry and fluorescence and confocal microscopy. Spirochetes were stained with a fluorescent membrane marker (PKH67 or PKH26), inoculated into 8 different tick cell lines and incubated at 30°C for 24 h. PKH efficiently stained B. burgdorferi without affecting bacterial viability or motility. Among the tick cell lines tested, the Rhipicephalus appendiculatus cell line RA243 achieved the highest percentage of association/internalization, with both high (90%) and low (10%) concentrations of BSK-H medium in tick cell culture medium. Treatment with cytochalasin D dramatically reduced the average percentage of cells with internalized spirochetes, which passed through a dramatic morphological change during their internalization by the host cell as observed in time-lapse photography. Almost all of the fluorescent bacteria were seen to be inside the tick cells. PKH labeling of borreliae proved to be a reliable and valuable tool to analyze the association of spirochetes with host cells by flow cytometry, confocal and fluorescence microscopy. PMID:27332772

  9. Occurrence of Borrelia burgdorferi s.l. in different genera of mosquitoes (Culicidae) in Central Europe.

    PubMed

    Melaun, Christian; Zotzmann, Sina; Santaella, Vanesa Garcia; Werblow, Antje; Zumkowski-Xylander, Helga; Kraiczy, Peter; Klimpel, Sven

    2016-03-01

    Lyme disease or Lyme borreliosis is a vector-borne infectious disease caused by spirochetes of the Borrelia burgdorferi sensu lato complex. Some stages of the borrelial transmission cycle in ticks (transstadial, feeding and co-feeding) can potentially occur also in insects, particularly in mosquitoes. In the present study, adult as well as larval mosquitoes were collected at 42 different geographical locations throughout Germany. This is the first study, in which German mosquitoes were analyzed for the presence of Borrelia spp. Targeting two specific borrelial genes, flaB and ospA encoding for the subunit B of flagellin and the outer surface protein A, the results show that DNA of Borrelia afzelii, Borrelia bavariensis and Borrelia garinii could be detected in ten Culicidae species comprising four distinct genera (Aedes, Culiseta, Culex, and Ochlerotatus). Positive samples also include adult specimens raised in the laboratory from wild-caught larvae indicating that transstadial and/or transovarial transmission might occur within a given mosquito population.

  10. GAPDH gene diversity in spirochetes: a paradigm for genetic promiscuity.

    PubMed

    Figge, R M; Cerff, R

    2001-12-01

    In this study we have determined gap sequences from nine different spirochetes. Phylogenetic analyses of these sequences in the context of all other available eubacterial and a selection of eukaryotic Gap sequences demonstrated that the eubacterial glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene diversity encompasses at least five highly distinct gene families. Within these gene families, spirochetes show an extreme degree of sequence divergence that is probably the result of several lateral gene transfer events between spirochetes and other eubacterial phyla, and early gene duplications in the eubacterial ancestor. A Gap1 sequence from the syphilis spirochete Treponema pallidum has recently been shown to be closely related to GapC sequences from Euglenozoa. Here we demonstrate that several other spirochetal species are part of this cluster, supporting the conclusion that an interkingdom gene transfer from spirochetes to Euglenozoa must have occurred. Furthermore, we provide evidence that the GAPDH genes present in the protists Parabasalia may also be of spirochetal descent.

  11. Rickettsiae and Borrelia burgdorferi in ixodid ticks.

    PubMed Central

    Magnarelli, L A; Andreadis, T G; Stafford, K C; Holland, C J

    1991-01-01

    Nymphs and adults of hard-bodied ticks were collected in Connecticut and tested by direct and indirect immunofluorescence staining methods for rickettsiae and Borrelia burgdorferi. Of the 609 Ixodes dammini ticks examined, 59 (9.7%) harbored rickettsialike microorganisms in hemocytes (blood cells). These bacteria reacted with fluorescein-conjugated antiserum to Ehrlichia canis, the etiologic agent of with fluorescein-conjugated antiserum to Ehrlichia canis, the etiologic agent of canine ehrlichiosis. Prevalence of infection ranged from 6.8 to 12.7% for males and females, respectively. Although the specific identities of the hemocytic rickettsialike organisms are unknown, they share antigens with ehrlichiae. Electron microscopy revealed rickettsiae in ovarian tissues of I. dammini that also had infected hemocytes. Rickettsialike organisms were also observed in the hemocytes of 5 (6.9%) of 73 Dermacentor variabilis ticks. In analyses for B. burgdorferi, 146 (23.7%) of 617 I. dammini ticks harbored these spirochetes in midguts. Hemocytic rickettsialike microorganisms coexisted with B. burgdorferi in 36 (6.7%) of the 537 nymphs and adults of I. dammini examined. I. dammini, with its broad host range, has the potential to acquire multiple microorganisms. Images PMID:1757551

  12. Culturing Borrelia burgdorferi from spleen and kidney tissues of wild-caught white-footed mice, Peromyscus leucopus.

    PubMed

    Anderson, J F; Johnson, R C; Magnarelli, L A; Hyde, F W

    1986-12-01

    Borrelia burgdorferi was isolated most frequently from tissue of spleen (n = 13) and kidney (n = 10) and less often from blood (n = 5) of wild-caught Peromyscus leucopus. Prevalence of infection tended to be highest at sites where Lyme disease was most common (e.g., 5 of 6 mice were positive in East Haddam, Connecticut). Spirochetes were not isolated in Danbury or New Hartford, areas where this malady is rare. However, in Fairfield, where the disease is also uncommon, 4 of 9 mice were infected. Larval and nymphal I. dammini, containing borreliae, parasitized P. leucopus at all sites where B. burgdorferi was cultured from mice. Borreliae were also detected in D. variabilis feeding on hosts at two of the sites. P. leucopus appears to be an excellent animal to identify focal areas of B. burgdorferi.

  13. Bacterial Heterogeneity Is a Requirement for Host Superinfection by the Lyme Disease Spirochete

    PubMed Central

    Rogovskyy, Artem S.

    2014-01-01

    In nature, mixed Borrelia burgdorferi infections are common and possibly can be acquired by either superinfection or coinfection. Superinfection by heterologous B. burgdorferi strains has been established experimentally, although the ability of homologous B. burgdorferi clones to superinfect a host has not been studied in detail. Information regarding any potential immune barriers to secondary infection also currently is unavailable. In the present study, the ability to superinfect various mouse models by homologous wild-type clones was examined and compared to superinfection by heterologous strains. To assess the ability of homologous B. burgdorferi clones to successfully superinfect a mouse host, primary- and secondary-infecting spirochetes were recovered via in vitro cultivation of collected blood or tissue samples. This was accomplished by generating two different antibiotic-resistant versions of the wild-type B31-A3 clone in order to distinguish superinfecting B. burgdorferi from primary-infecting spirochetes. The data demonstrate an inability of homologous B. burgdorferi to superinfect immunocompetent mice as opposed to heterologous strains. Attempts to superinfect different types of immunodeficient mice with homologous B. burgdorferi indicate that the murine innate immune system represents a major barrier to intrastrain superinfection. Consequently, the possibility of innate immunity as a driving force for B. burgdorferi heterogeneity during the enzootic cycle is discussed. PMID:25114120

  14. Versatile roles of CspA orthologs in complement inactivation of serum-resistant Lyme disease spirochetes.

    PubMed

    Hammerschmidt, Claudia; Koenigs, Arno; Siegel, Corinna; Hallström, Teresia; Skerka, Christine; Wallich, Reinhard; Zipfel, Peter F; Kraiczy, Peter

    2014-01-01

    CspA of the Lyme disease spirochete Borrelia burgdorferi represents a key molecule in immune evasion, protecting borrelial cells from complement-mediated killing. As previous studies focused almost exclusively on CspA of B. burgdorferi, here we investigate the different binding capacities of CspA orthologs of Borrelia burgdorferi, B. afzelii, and B. spielmanii for complement regulator factor H and plasminogen and their ability to inhibit complement activation by either binding these host-derived plasma proteins or independently by direct interaction with components involved in formation of the lethal, pore-like terminal complement complex. To further examine their function in serum resistance in vivo, a serum-sensitive B. garinii strain was used to generate spirochetes, ectopically producing functional CspA orthologs. Irrespective of their species origin, all three CspA orthologs impart resistance to complement-mediated killing when produced in a serum-sensitive B. garinii surrogate strain. To analyze the inhibitory effect on complement activation and to assess the potential to inactivate C3b by binding of factor H and plasminogen, recombinant CspA orthologs were also investigated. All three CspA orthologs simultaneously bound factor H and plasminogen but differed in regard to their capacity to inactivate C3b via bound plasmin(ogen) and inhibit formation of the terminal complement complex. CspA of B. afzelii binds plasmin(ogen) and inhibits the terminal complement complex more efficiently than CspA of B. burgdorferi and B. spielmanii. Taken together, CspA orthologs of serum-resistant Lyme disease spirochetes act as multifunctional evasion molecules that inhibit complement on two central activation levels, C3b generation and assembly of the terminal complement complex.

  15. Versatile Roles of CspA Orthologs in Complement Inactivation of Serum-Resistant Lyme Disease Spirochetes

    PubMed Central

    Hammerschmidt, Claudia; Koenigs, Arno; Siegel, Corinna; Hallström, Teresia; Skerka, Christine; Wallich, Reinhard; Zipfel, Peter F.

    2014-01-01

    CspA of the Lyme disease spirochete Borrelia burgdorferi represents a key molecule in immune evasion, protecting borrelial cells from complement-mediated killing. As previous studies focused almost exclusively on CspA of B. burgdorferi, here we investigate the different binding capacities of CspA orthologs of Borrelia burgdorferi, B. afzelii, and B. spielmanii for complement regulator factor H and plasminogen and their ability to inhibit complement activation by either binding these host-derived plasma proteins or independently by direct interaction with components involved in formation of the lethal, pore-like terminal complement complex. To further examine their function in serum resistance in vivo, a serum-sensitive B. garinii strain was used to generate spirochetes, ectopically producing functional CspA orthologs. Irrespective of their species origin, all three CspA orthologs impart resistance to complement-mediated killing when produced in a serum-sensitive B. garinii surrogate strain. To analyze the inhibitory effect on complement activation and to assess the potential to inactivate C3b by binding of factor H and plasminogen, recombinant CspA orthologs were also investigated. All three CspA orthologs simultaneously bound factor H and plasminogen but differed in regard to their capacity to inactivate C3b via bound plasmin(ogen) and inhibit formation of the terminal complement complex. CspA of B. afzelii binds plasmin(ogen) and inhibits the terminal complement complex more efficiently than CspA of B. burgdorferi and B. spielmanii. Taken together, CspA orthologs of serum-resistant Lyme disease spirochetes act as multifunctional evasion molecules that inhibit complement on two central activation levels, C3b generation and assembly of the terminal complement complex. PMID:24191298

  16. Serologic analyses of Peromyscus leucopus, a rodent reservoir for Borrelia burgdorferi, in northeastern United States.

    PubMed

    Magnarelli, L A; Anderson, J F; Hyland, K E; Fish, D; Mcaninch, J B

    1988-06-01

    An enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent-antibody test were used to detect antibodies to Borrelia burgdorferi, the causative agent of Lyme disease, in Peromyscus leucopus (white-footed mouse). Of the 661 mice captured in Connecticut, Rhode Island, and New York during 1980 and 1983 to 1987, 166 (25.1%) had antibodies to B. burgdorferi by ELISA. Comparative analyses of 210 serum specimens, collected in areas where Lyme disease is endemic, revealed a threefold difference in sensitivity between the ELISA (38.1% positive) and the indirect fluorescent-antibody method (12.4%). Although prevalence of seropositive P. leucopus was highest during June, elevated amounts of antibody (1:1,280 to 1:2,560) were detected in mice that harbored spirochetes during all seasons. Being reservoirs for B. burgdorferi, these rodents are suitable for monitoring spirochete infections at foci and should be included in field evaluations of control programs aimed at suppressing Lyme disease.

  17. Borrelia sp. in ticks recovered from white-tailed deer in Alabama.

    PubMed

    Luckhart, S; Mullen, G R; Durden, L A; Wright, J C

    1992-07-01

    Six hundred sixty-five hunter-killed white-tailed deer (Odocoileus virginianus) from 18 counties in Alabama (USA) were examined for ticks. Most of the collections were made at state-operated wildlife management areas. Four species of ticks (n = 4,527) were recovered: the lone star tick Amblyomma americanum (n = 482); the Gulf Coast tick A. maculatum (n = 11); the winter tick Dermacentor albipictus (n = 1,242); and the black-legged tick Ixodes scapularis (n = 2,792). Fifty-six percent of the ticks (n = 2,555) were examined for Borrelia sp. spirochetes using an immunofluorescent, polyclonal antibody assay. Spirochetes were detected in I. scapularis (five females, seven males) from Barbour, Butler, Coosa, and Lee counties and A. americanum (four males, four nymphs) from Hale, Lee, and Wilcox counties. Area-specific prevalences in ticks were as high as 3.3% for I. scapularis and 3.8% for A. americanum.

  18. Vaccination against Lyme disease caused by diverse Borrelia burgdorferi.

    PubMed

    Fikrig, E; Telford, S R; Wallich, R; Chen, M; Lobet, Y; Matuschka, F R; Kimsey, R B; Kantor, F S; Barthold, S W; Spielman, A; Flavell, R A

    1995-01-01

    Diversity and mutations in the genes for outer surface proteins (Osps) A and B of Borrelia burgdorferi sensu lato (B. burgdorferi), the spirochetal agent of Lyme disease, suggests that a monovalent OspA or OspB vaccine may not provide protection against antigenically variable naturally occurring B. burgdorferi. We now show that OspA or OspB immunizations protect mice from tick-borne infection with heterogeneous B. burgdorferi from different geographic regions. This result is in distinct contrast to in vitro killing analyses and in vivo protection studies using syringe injections of B. burgdorferi as the challenge inoculum. Evaluations of vaccine efficacy against Lyme disease and other vector-borne infections should use the natural mode of transmission and not be predicated on classification systems or assays that do not rely upon the vector to transmit infection.

  19. New Borrelia species detected in ixodid ticks in Oromia, Ethiopia.

    PubMed

    Kumsa, Bersissa; Socolovschi, Cristina; Raoult, Didier; Parola, Philippe

    2015-04-01

    Little is known about Borrelia species transmitted by hard ticks in Ethiopia. The present study was conducted from November 2011 through March 2014 to address the occurrence and molecular identity of these bacteria in ixodid ticks infesting domestic animals in Oromia, Ethiopia. A total of 767 ixodid ticks collected from domestic animals were screened for Borrelia DNA by quantitative (q) real-time PCR followed by standard PCR and sequencing to identify the species. Overall, 3.8% (29/767) of the tested ticks were positive for Borrelia DNA, including 8/119 (6.7%) Amblyomma cohaerens, 1/42 (2.4%) Am. gemma, 3/53 (5.7%) Am. variegatum, 5/22 (22.7%) Amblyomma larvae, 3/60 (5%) Amblyomma nymphs, 2/139 (1.4%) Rhipicephalus (Boophilus) decoloratus, 2/31 (6.4%) Rh. decoloratus nymphs, and 5/118 (4.2%) Rh. pulchellus using 16S genus-specific qPCR. The prevalence of Borrelia DNA was significantly higher in genus Amblyomma (20/298, 6.7%) than in the genus Rhipicephalus (9/417, 2.1%) ticks (P=0.001). Sequencing of PCR products from the flaB and 16S rRNA genes of Borrelia spp. from Amblyomma ticks showed the presence of a new species between the relapsing fever and Lyme disease groups. However, Borrelia sp. detected in Rhipicephalus ticks clustered with B. theileri/B. lonestari. The human pathogenicity of the Borrelia sp. detected in Amblyomma ticks from Ethiopia has not yet been investigated, whereas the Borrelia sp. detected in Rhipicephalus ticks in our study is the causative agent of bovine borreliosis in cattle and may have veterinary importance in different parts of Ethiopia. Furthermore, the detection of previously unrecognized Borrelia species in Amblyomma and Rhipicephalus ticks in Ethiopia generates additional questions concerning the bacterial fauna in hard ticks and will prompt researchers to perform detailed studies for better understanding of ixodid ticks associated bacteria.

  20. New Borrelia species detected in ixodid ticks in Oromia, Ethiopia.

    PubMed

    Kumsa, Bersissa; Socolovschi, Cristina; Raoult, Didier; Parola, Philippe

    2015-04-01

    Little is known about Borrelia species transmitted by hard ticks in Ethiopia. The present study was conducted from November 2011 through March 2014 to address the occurrence and molecular identity of these bacteria in ixodid ticks infesting domestic animals in Oromia, Ethiopia. A total of 767 ixodid ticks collected from domestic animals were screened for Borrelia DNA by quantitative (q) real-time PCR followed by standard PCR and sequencing to identify the species. Overall, 3.8% (29/767) of the tested ticks were positive for Borrelia DNA, including 8/119 (6.7%) Amblyomma cohaerens, 1/42 (2.4%) Am. gemma, 3/53 (5.7%) Am. variegatum, 5/22 (22.7%) Amblyomma larvae, 3/60 (5%) Amblyomma nymphs, 2/139 (1.4%) Rhipicephalus (Boophilus) decoloratus, 2/31 (6.4%) Rh. decoloratus nymphs, and 5/118 (4.2%) Rh. pulchellus using 16S genus-specific qPCR. The prevalence of Borrelia DNA was significantly higher in genus Amblyomma (20/298, 6.7%) than in the genus Rhipicephalus (9/417, 2.1%) ticks (P=0.001). Sequencing of PCR products from the flaB and 16S rRNA genes of Borrelia spp. from Amblyomma ticks showed the presence of a new species between the relapsing fever and Lyme disease groups. However, Borrelia sp. detected in Rhipicephalus ticks clustered with B. theileri/B. lonestari. The human pathogenicity of the Borrelia sp. detected in Amblyomma ticks from Ethiopia has not yet been investigated, whereas the Borrelia sp. detected in Rhipicephalus ticks in our study is the causative agent of bovine borreliosis in cattle and may have veterinary importance in different parts of Ethiopia. Furthermore, the detection of previously unrecognized Borrelia species in Amblyomma and Rhipicephalus ticks in Ethiopia generates additional questions concerning the bacterial fauna in hard ticks and will prompt researchers to perform detailed studies for better understanding of ixodid ticks associated bacteria. PMID:25843811

  1. Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector▿

    PubMed Central

    Battisti, James M.; Bono, James L.; Rosa, Patricia A.; Schrumpf, Merry E.; Schwan, Tom G.; Policastro, Paul F.

    2008-01-01

    The Lyme disease spirochete Borrelia burgdorferi alters the expression of outer surface protein (osp) genes as the bacterium cycles between ticks and mammals. OspA is produced as borreliae enter the tick vector and remains a major surface antigen during midgut colonization. To elucidate the role of OspA in the vector, we created an insertional deletion of ospA in strain B31-A3. The ospA mutant infects mice when it is injected intradermally and is acquired by larval ticks fed on these mice, where it persists through the molt to the nymph stage. Bacterial survival rates in artificially infected tick larvae fed on naïve mice were compared with those in the vector fed on immune mice. The ospA mutant proliferates in larvae if it is exposed to blood from naïve mice, but it declines in density after larval feeding if the blood is from immune mice. When uninfected larvae are fed on B-cell-deficient mice infected with the ospA mutant, larvae show borrelial densities and persistence that are significantly greater than those fed on infected, immunocompetent mice. We conclude that OspA serves a critical antibody-shielding role during vector blood meal uptake from immune hosts and is not required for persistence in the tick vector. PMID:18779341

  2. Western gray squirrel (Rodentia: Sciuridae): a primary reservoir host of Borrelia burgdorferi in Californian oak woodlands?

    PubMed

    Lane, Robert S; Mun, Jeomhee; Eisen, Rebecca J; Eisen, Lars

    2005-05-01

    In California, dense woodlands have been recognized as important biotopes where humans are exposed to the nymphal stage of the western blacklegged tick, Ixodes pacificus Cooley & Kohls, the primary vector of the Lyme disease spirochete Borrelia burgdorferi sensu stricto (s.s.), in the far-western United States. To identify the principal reservoir host(s) of this spirochete, and of closely related spirochetes in the B. burgdorferi sensu lato (s.l.) complex, in dense woodlands in Mendocino County, California, approximately 50 species of birds and mammals, including wood rats and kangaroo rats, were evaluated as potential hosts for vector ticks and borreliae in 2002 and 2003. Although polymerase chain reaction (PCR) and sequencing analyses revealed that many vertebrate species had been exposed to one or more members of the B. burgdorferi s.l. spirochetal complex, only the western gray squirrel, Sciurus griseus, fulfilled the major criteria for a reservoir host of B. burgdorferi s.s. Ear-punch biopsies from eight of 10 squirrels collected from five separate woodlands were PCR-positive for B. burgdorferi s.s., 47% of I. pacificus larvae (n = 64) and 31% of nymphs (n = 49) removed from squirrels contained B. burgdorferi s.l., and the engorgement status of I. pacificus larvae was associated positively with acquisition of spirochetes. Overall, 83 and 100% of the amplicons sequenced from PCR-positive I. pacificus larvae and nymphs, respectively, were identified as B. burgdorferi s.s, Among the five remaining positive I. pacificus larvae, three contained B. bissettii and two had uncharacterized B. burgdorferi s.l. Borrelia burgdorferi s.s. was detected in one of five larvae and zero of two nymphs of the Pacific Coast tick, Dermacentor occidentalis Marx, that likewise had been removed from squirrels. The rickettsial agent of human anaplasmosis, Anaplasma phagocytophilum, was detected in the blood or ear biopsies of two squirrels and in one (1.6%) of 64 I. pacificus larvae and

  3. Identification of Borrelia Species after Creation of an In-House MALDI-TOF MS Database

    PubMed Central

    Calderaro, Adriana; Gorrini, Chiara; Piccolo, Giovanna; Montecchini, Sara; Buttrini, Mirko; Rossi, Sabina; Piergianni, Maddalena; Arcangeletti, Maria Cristina; De Conto, Flora; Chezzi, Carlo; Medici, Maria Cristina

    2014-01-01

    Lyme borreliosis (LB) is a multisystemic disease caused by Borrelia burgdorferi sensu lato (sl) complex transmitted to humans by Ixodes ticks. B. burgdorferi sl complex, currently comprising at least 19 genospecies, includes the main pathogenic species responsible for human disease in Europe: B. burgdorferi sensu stricto (ss), B. afzelii, and B. garinii. In this study, for the first time, MALDI-TOF MS was applied to Borrelia spp., supplementing the existing database, limited to the species B. burgdorferi ss, B. spielmanii and B. garinii, with the species B. afzelii, in order to enable the identification of all the species potentially implicated in LB in Europe. Moreover, we supplemented the database also with B. hermsii, which is the primary cause of tick-borne relapsing fever in western North America, B. japonica, circulating in Asia, and another reference strain of B. burgdorferi ss (B31 strain). The dendrogram obtained by analyzing the protein profiles of the different Borrelia species reflected Borrelia taxonomy, showing that all the species included in the Borrelia sl complex clustered in a unique branch, while Borrelia hermsii clustered separately. In conclusion, in this study MALDI-TOF MS proved a useful tool suitable for identification of Borrelia spp. both for diagnostic purpose and epidemiological surveillance. PMID:24533160

  4. Isolation of the Lyme disease spirochete from mammals in Minnesota.

    PubMed

    Loken, K I; Wu, C C; Johnson, R C; Bey, R F

    1985-07-01

    Lyme disease spirochetes were isolated from the kidneys of two Peromyscus spp. trapped in Minnesota in September and October 1983. No spirochetes were isolated from white-tailed deer (Odocoileus virginianus), red backed voles (Clethrionomys gapperi), or shrews (Sorexy cinereus and Blarina brevicauda). This is the first report of the isolation of the Lyme disease spirochete from the midwestern United States and isolations from these animals, which were free of ticks, suggest that the Lyme disease spirochete may persist in animal organs for months. PMID:4001130

  5. Proteomic Analysis of Lyme Disease: Global Protein Comparison of Three Strains of Borrelia burgdorferi

    SciTech Connect

    Jacobs, Jon M.; Yang, Xiaohua; Luft, Benjamin J.; Dunn, John J.; Camp, David G.; Smith, Richard D.

    2005-04-01

    The Borrelia burgdorferi spirochete is the causative agent of Lyme disease, the most common tick-borne disease in the United States. It has been studied extensively to help understand its pathogenicity of infection and how it can persist in different mammalian hosts. We report the proteomic analysis of the archetype B. burgdorferi B31 strain and two other strains (ND40, and JD-1) having different Borrelia pathotypes using strong cation exchange fractionation of proteolytic peptides followed by high-resolution, reversed phase capillary liquid chromatography coupled with ion trap tandem mass spectrometric (LC-MS/MS) analysis. Protein identification was facilitated by the availability of the complete B31 genome sequence. A total of 665 Borrelia proteins were identified representing ~38 % coverage of the theoretical B31 proteome. A significant overlap was observed between the identified proteins in direct comparisons between any two strains (>72%), but distinct differences were observed among identified hypothetical and outer membrane proteins of the three strains. Such a concurrent proteomic overview of three Borrelia strains based upon only the B31 genome sequence is shown to provide significant insights into the presence or absence of specific proteins and a broad overall comparison among strains.

  6. Case Report: Bilateral diaphragmatic dysfunction due to Borrelia Burgdorferi

    PubMed Central

    Basunaid, Suhail; van der Grinten, Chris; Cobben, Nicole; Otte, Astrid; Sprooten, Roy; Gernot, Rohde

    2014-01-01

    Summary: In this case report we describe a rare case of bilateral diaphragmatic dysfunction due to Lyme disease. Case report: A 62-years-old male presented to the hospital because of flu-like symptoms. During initial evaluation a bilateral diaphragmatic weakness with orthopnea and nocturnal hypoventilation was observed, without a known aetiology. Bilateral diaphragmatic paralysis was confirmed by fluoroscopy with a positive sniff test. The patient was referred to our centre for chronic non-invasive nocturnal ventilation (cNPPV). Subsequent investigations revealed evidence of anti- Borrelia seroactivity in EIA-IgG and IgG-blot, suggesting a recent infection with Lyme disease, and resulted in a 4-week treatment with oral doxycycline. The symptoms of nocturnal hypoventilation were successfully improved with cNPPV. However, our patient still shows impaired diaphragmatic function but he is no longer fully dependent on nocturnal ventilatory support.     Conclusion: Lyme disease should be considered in the differential diagnosis of diaphragmatic dysfunction. It is a tick-borne illness caused by one of the three pathogenic species of the spirochete Borrelia burgdorferi, present in Europe. A delay in recognizing the symptoms can negatively affect the success of treatment. Non-invasive mechanical ventilation (NIV) is considered a treatment option for patients with diaphragmatic paralysis. PMID:25671085

  7. Cross-reactive acquired immunity influences transmission success of the Lyme disease pathogen, Borrelia afzelii.

    PubMed

    Jacquet, Maxime; Durand, Jonas; Rais, Olivier; Voordouw, Maarten J

    2015-12-01

    Cross-reactive acquired immunity in the vertebrate host induces indirect competition between strains of a given pathogen species and is critical for understanding the ecology of mixed infections. In vector-borne diseases, cross-reactive antibodies can reduce pathogen transmission at the vector-to-host and the host-to-vector lifecycle transition. The highly polymorphic, immunodominant, outer surface protein C (OspC) of the tick-borne spirochete bacterium Borrelia afzelii induces a strong antibody response in the vertebrate host. To test how cross-immunity in the vertebrate host influences tick-to-host and host-to-tick transmission, mice were immunized with one of two strain-specific recombinant OspC proteins (A3, A10), challenged via tick bite with one of the two B. afzelii ospC strains (A3, A10), and infested with xenodiagnostic ticks. Immunization with a given rOspC antigen protected mice against homologous strains carrying the same major ospC group allele but provided little or no cross-protection against heterologous strains carrying a different major ospC group allele. There were cross-immunity effects on the tick spirochete load but not on the probability of host-to-tick transmission. The spirochete load in ticks that had fed on mice with cross-immune experience was reduced by a factor of two compared to ticks that had fed on naive control mice. In addition, strain-specific differences in mouse spirochete load, host-to-tick transmission, tick spirochete load, and the OspC-specific IgG response revealed the mechanisms that determine variation in transmission success between strains of B. afzelii. This study shows that cross-immunity in infected vertebrate hosts can reduce pathogen load in the arthropod vector with potential consequences for vector-to-host pathogen transmission.

  8. Cross-reactive acquired immunity influences transmission success of the Lyme disease pathogen, Borrelia afzelii.

    PubMed

    Jacquet, Maxime; Durand, Jonas; Rais, Olivier; Voordouw, Maarten J

    2015-12-01

    Cross-reactive acquired immunity in the vertebrate host induces indirect competition between strains of a given pathogen species and is critical for understanding the ecology of mixed infections. In vector-borne diseases, cross-reactive antibodies can reduce pathogen transmission at the vector-to-host and the host-to-vector lifecycle transition. The highly polymorphic, immunodominant, outer surface protein C (OspC) of the tick-borne spirochete bacterium Borrelia afzelii induces a strong antibody response in the vertebrate host. To test how cross-immunity in the vertebrate host influences tick-to-host and host-to-tick transmission, mice were immunized with one of two strain-specific recombinant OspC proteins (A3, A10), challenged via tick bite with one of the two B. afzelii ospC strains (A3, A10), and infested with xenodiagnostic ticks. Immunization with a given rOspC antigen protected mice against homologous strains carrying the same major ospC group allele but provided little or no cross-protection against heterologous strains carrying a different major ospC group allele. There were cross-immunity effects on the tick spirochete load but not on the probability of host-to-tick transmission. The spirochete load in ticks that had fed on mice with cross-immune experience was reduced by a factor of two compared to ticks that had fed on naive control mice. In addition, strain-specific differences in mouse spirochete load, host-to-tick transmission, tick spirochete load, and the OspC-specific IgG response revealed the mechanisms that determine variation in transmission success between strains of B. afzelii. This study shows that cross-immunity in infected vertebrate hosts can reduce pathogen load in the arthropod vector with potential consequences for vector-to-host pathogen transmission. PMID:26384476

  9. Isolation of Lyme disease Borrelia from puffins (Fratercula arctica) and seabird ticks (Ixodes uriae) on the Faeroe Islands.

    PubMed

    Gylfe; Olsen, B; Strasevicius, D; Marti Ras, N; Weihe, P; Noppa, L; Ostberg, Y; Baranton, G; Bergström, S

    1999-04-01

    This is the first report on the isolation of Lyme disease Borrelia from seabirds on the Faeroe Islands and the characteristics of its enzootic cycle. The major components of the Borrelia cycle include the puffin (Fratercula arctica) as the reservoir and Ixodes uriae as the vector. The importance of this cycle and its impact on the spread of human Lyme borreliosis have not yet been established. Borrelia spirochetes isolated from 2 of 102 sampled puffins were compared to the borreliae previously obtained from seabird ticks, I. uriae. The rrf-rrl intergenic spacer and the rrs and the ospC genes were sequenced and a series of phylogenetic trees were constructed. Sequence data and restriction fragment length polymorphism analysis grouped the strains together with Borrelia garinii. In a seroepidemiological survey performed with residents involved in puffin hunting on the Faeroe Islands, 3 of 81 serum samples were found to be positive by two commonly used clinical tests: a flagellin-based enzyme-linked immunosorbent assay (ELISA) and Western blotting. These three positive serum samples also had high optical density values in a whole-cell ELISA. The finding of seropositive Faeroe Islanders who are regularly exposed to I. uriae indicate that there may be a transfer of B. garinii by this tick species to humans. PMID:10074497

  10. Comparison of different strains of Borrelia burgdorferi sensu lato used as antigens in enzyme-linked immunosorbent assays.

    PubMed Central

    Magnarelli, L A; Anderson, J F; Johnson, R C; Nadelman, R B; Wormser, G P

    1994-01-01

    Eight strains of Borrelia burgdorferi sensu lato were tested with serum samples from persons who had Lyme borreliosis or syphilis in class-specific enzyme-linked immunosorbent assays (ELISAs). Antigens of B. burgdorferi sensu stricto, of Borrelia garinii, and of Borrelia spirochetes in group VS461 were prepared from cultured bacteria isolated from ticks, a white-footed mouse (Peromyscus leucopus), or human tissues in North America, the former Soviet Union, and Japan. Nearly all of the serum specimens that contained immunoglobulins to strain 2591, a Connecticut isolate, were also positive in antibody tests with the other seven strains. In general, all eight strains reacted similarly and were suitable as coating antigens in class-specific ELISAs. Assay sensitivities ranged from 82.6 to 100% in analyses for immunoglobulin M and G antibodies. Compared with reference antigen strain 2591, strains 231 (a tick isolate from Canada) and NCH-1 (a human skin isolate from Wisconsin) resulted in higher antibody titers in an ELISA. Syphilitic sera cross-reacted in all tests regardless of the antigen used. Key immunodominant proteins are shared among the closely related strains of B. burgdorferi sensu lato tested, but it is suspected that variations in antigen compositions among these spirochetes may sometimes affect assay performance for detecting serum antibodies. PMID:8051239

  11. First detection of Borrelia burgdorferi sensu lato DNA in king penguins (Aptenodytes patagonicus halli).

    PubMed

    Schramm, Frédéric; Gauthier-Clerc, Michel; Fournier, Jean-Charles; McCoy, Karen D; Barthel, Cathy; Postic, Danièle; Handrich, Yves; Le Maho, Yvon; Jaulhac, Benoît

    2014-10-01

    The hard tick Ixodes uriae parasitises a wide range of seabird species in the circumpolar areas of both Northern and Southern hemispheres and has been shown to be infected with Borrelia burgdorferi sensu lato, the bacterial agents of Lyme borreliosis. Although it is assumed that seabirds represent viable reservoir hosts, direct demonstrations of infection are limited to a single study from the Northern hemisphere. Here, the blood of 50 tick-infested adult king penguins (Aptenodytes patagonicus halli) breeding in the Crozet Archipelago (Southern Indian Ocean) was examined for B. burgdorferi sl exposure by serology and for spirochetemia by in vitro DNA amplification. Four birds were found positive by serology, whereas B. burgdorferi sl DNA was detected in two other birds. Our data therefore provide the first direct proof of Borrelia burgdorferi sl spirochetes in seabirds of the Southern hemisphere and indicate a possible reservoir role for king penguins in the natural maintenance of this bacterium. Although the bacterial genetic diversity present in these hosts and the infectious period for tick vectors remain to be elucidated, our results add to a growing body of knowledge on the contribution of seabirds to the complex epizootiology of Lyme disease and the global dissemination of B. burgdorferi sl spirochetes. PMID:25150726

  12. Efficacy of an experimental azithromycin cream for prophylaxis of tick-transmitted lyme disease spirochete infection in a murine model.

    PubMed

    Piesman, Joseph; Hojgaard, Andrias; Ullmann, Amy J; Dolan, Marc C

    2014-01-01

    As an alternative to oral prophylaxis for the prevention of tick transmission of Borrelia burgdorferi, we tested antibiotic cream prophylactic formulations in a murine model of spirochete infection. A 4% preparation of doxycycline cream afforded no protection, but a single application of 4% azithromycin cream was 100% protective when applied directly to the tick bite site at the time of tick removal. Indeed, the azithromycin cream was 100% effective when applied at up to 3 days after tick removal and protected 74% of mice exposed to tick bite when applied at up to 2 weeks after tick removal. Azithromycin cream was also protective when applied at a site distal to the tick bite site, suggesting that it was having a systemic effect in addition to a local transdermal effect. Mice that were protected from tick-transmitted infection did not seroconvert and did not infect larval ticks on xenodiagnosis. Azithromycin cream formulations appear to hold promise for Lyme disease prophylaxis. PMID:24165183

  13. Efficacy of an experimental azithromycin cream for prophylaxis of tick-transmitted lyme disease spirochete infection in a murine model.

    PubMed

    Piesman, Joseph; Hojgaard, Andrias; Ullmann, Amy J; Dolan, Marc C

    2014-01-01

    As an alternative to oral prophylaxis for the prevention of tick transmission of Borrelia burgdorferi, we tested antibiotic cream prophylactic formulations in a murine model of spirochete infection. A 4% preparation of doxycycline cream afforded no protection, but a single application of 4% azithromycin cream was 100% protective when applied directly to the tick bite site at the time of tick removal. Indeed, the azithromycin cream was 100% effective when applied at up to 3 days after tick removal and protected 74% of mice exposed to tick bite when applied at up to 2 weeks after tick removal. Azithromycin cream was also protective when applied at a site distal to the tick bite site, suggesting that it was having a systemic effect in addition to a local transdermal effect. Mice that were protected from tick-transmitted infection did not seroconvert and did not infect larval ticks on xenodiagnosis. Azithromycin cream formulations appear to hold promise for Lyme disease prophylaxis.

  14. Motility is crucial for the infectious life cycle of Borrelia burgdorferi.

    PubMed

    Sultan, Syed Z; Manne, Akarsh; Stewart, Philip E; Bestor, Aaron; Rosa, Patricia A; Charon, Nyles W; Motaleb, M A

    2013-06-01

    The Lyme disease spirochete, Borrelia burgdorferi, exists in a zoonotic cycle involving an arthropod tick and mammalian host. Dissemination of the organism within and between these hosts depends upon the spirochete's ability to traverse through complex tissues. Additionally, the spirochete outruns the host immune cells while migrating through the dermis, suggesting the importance of B. burgdorferi motility in evading host clearance. B. burgdorferi's periplasmic flagellar filaments are composed primarily of a major protein, FlaB, and minor protein, FlaA. By constructing a flaB mutant that is nonmotile, we investigated for the first time the absolute requirement for motility in the mouse-tick life cycle of B. burgdorferi. We found that whereas wild-type cells are motile and have a flat-wave morphology, mutant cells were nonmotile and rod shaped. These mutants were unable to establish infection in C3H/HeN mice via either needle injection or tick bite. In addition, these mutants had decreased viability in fed ticks. Our studies provide substantial evidence that the periplasmic flagella, and consequently motility, are critical not only for optimal survival in ticks but also for infection of the mammalian host by the arthropod tick vector. PMID:23529620

  15. Signaling through CD14 attenuates the inflammatory response to Borrelia burgdorferi, the agent of Lyme disease.

    PubMed

    Benhnia, Mohammed Rafii-El-Idrissi; Wroblewski, Danielle; Akhtar, Muhammad Naveed; Patel, Raina A; Lavezzi, Wendy; Gangloff, Sophie C; Goyert, Sanna M; Caimano, Melissa J; Radolf, Justin D; Sellati, Timothy J

    2005-02-01

    Lyme disease is a chronic inflammatory disorder caused by the spirochetal bacterium, Borrelia burgdorferi. In vitro evidence suggests that binding of spirochetal lipoproteins to CD14, a pattern recognition receptor expressed on monocytes/macrophages and polymorphonuclear cells, is a critical requirement for cellular activation and the subsequent release of proinflammatory cytokines that most likely contribute to symptomatology and clinical manifestations. To test the validity of this notion, we assessed the impact of CD14 deficiency on Lyme disease in C3H/HeN mice. Contrary to an anticipated diminution in pathology, CD14(-/-) mice exhibited more severe and persistent inflammation than did CD14(+/+) mice. This disparity reflects altered gene regulation within immune cells that may engender the higher bacterial burden and serum cytokine levels observed in CD14(-/-) mice. Comparing their in vitro stimulatory activity, live spirochetes, but not lysed organisms, were a potent CD14-independent stimulus of cytokine production, triggering an exaggerated response by CD14(-/-) macrophages. Collectively, our in vivo and in vitro findings support the provocative notion that: 1) pattern recognition by CD14 is entirely dispensable for elaboration of an inflammatory response to B. burgdorferi, and 2) CD14-independent signaling pathways are inherently more destructive than CD14-dependent pathways. Continued study of CD14-independent signaling pathways may provide mechanistic insight into the inflammatory processes that underlie development of chronic inflammation.

  16. Detection of Borrelia burgdorferi in urine of Peromyscus leucopus by inhibition enzyme-linked immunosorbent assay.

    PubMed

    Magnarelli, L A; Anderson, J F; Stafford, K C

    1994-03-01

    An inhibition enzyme-linked immunosorbent assay was developed to detect Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, in urine from white-footed mice (Peromyscus leucopus). Of the 87 urine specimens tested from 87 mice collected in widely separated tick-infested sites in Connecticut, 57 (65.5%) contained detectable concentrations of spirochetal antigens. Forty-seven (62.7%) of 75 serum samples analyzed contained antibodies to B. burgdorferi. In culture work with tissues from bladders, kidneys, spleens, or ears, 50 of 87 mice (57.5%) were infected with B. burgdorferi. Thirty-eight (76%) of 50 infected mice had antigens of this spirochete in urine, while 36 (72%) individuals had infected bladders. Of those with infected bladders, 24 (66.7%) mice excreted subunits or whole cells of B. burgdorferi into urine. Successful culturing of B. burgdorferi from mouse tissues, the presence of serum antibodies to this bacterium, and detection of antigens to this spirochete in urine provide further evidence that multiple assays can be performed to verify the presence of B. burgdorferi in P. leucopus.

  17. In vitro and in vivo induction of tumor necrosis factor alpha by Borrelia burgdorferi.

    PubMed Central

    Defosse, D L; Johnson, R C

    1992-01-01

    Tumor necrosis factor alpha (TNF-alpha) is an immunoregulatory cytokine with many biological activities including the mediation of inflammation. We examined sera and synovial fluids from patients seropositive for infection with Borrelia burgdorferi using a radioimmunoassay specific for TNF-alpha. Significant elevation of TNF-alpha was found in the sera and synovial fluids of patients examined, while controls showed no elevation. Sera of mice infected with B. burgdorferi contained elevated levels of TNF-alpha which varied during the course of a 24-day infection. To determine whether B. burgdorferi is capable of inducing TNF-alpha production, spirochetes were added to adherent human peripheral blood mononuclear cells or mouse peritoneal exudate cells and 24 h later supernatants were assayed. TNF-alpha induction occurred in a dose-dependent manner. The maximum stimulation occurred when a ratio of 1 to 10 spirochetes per mononuclear cell was used. At optimal concentrations, induction was not diminished by inactivation of spirochetes or pretreatment with polymyxin B. These results suggest that an increase in TNF-alpha production may occur as a result of infection with B. burgdorferi. PMID:1541526

  18. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease.

    PubMed

    Kalish, R A; McHugh, G; Granquist, J; Shea, B; Ruthazer, R; Steere, A C

    2001-09-15

    The interpretation of serological results for patients who had Lyme disease many years ago is not well defined. We studied the serological status of 79 patients who had had Lyme disease 10-20 years ago and did not currently have signs or symptoms of active Lyme disease. Of the 40 patients who had had early Lyme disease alone, 4 (10%) currently had IgM responses to Borrelia burgdorferi, and 10 (25%) still had IgG reactivity to the spirochete, as determined by a 2-test approach (enzyme-linked immunosorbent assay and Western blot). Of the 39 patients who had had Lyme arthritis, 6 (15%) currently had IgM responses and 24 (62%) still had IgG reactivity to the spirochete. IgM or IgG antibody responses to B. burgdorferi may persist for 10-20 years, but these responses are not indicative of active infection.

  19. Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes

    PubMed Central

    Maaz, Denny; Rausch, Sebastian; Richter, Dania; Krücken, Jürgen; Kühl, Anja A.; Demeler, Janina; Blümke, Julia; Matuschka, Franz-Rainer; von Samson-Himmelstjerna, Georg

    2016-01-01

    Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides. We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii. Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii. An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease. PMID:26883594

  20. Genetic Diversity of Borrelia burgdorferi and Detection of B. bissettii-Like DNA in Serum of North-Coastal California Residents▿

    PubMed Central

    Girard, Yvette A.; Fedorova, Natalia; Lane, Robert S.

    2011-01-01

    In North America, Lyme borreliosis (LB) is a tick-borne disease caused by infection with the spirochete Borrelia burgdorferi. We studied the genetic diversity of LB spirochetes in north-coastal California residents. Spirochete DNA was detected in 23.7% (27/114) of the study subjects using a PCR protocol optimized for increased sensitivity in human sera. Californians were most commonly infected with B. burgdorferi ospC genotype A, a globally widespread spirochete associated with high virulence in LB patients. Sequence analysis of rrf-rrl and p66 loci in 11% (3/27) of the PCR-positive study subjects revealed evidence of infection with an organism closely related to B. bissettii. This spirochete, heretofore associated with LB only in Europe, is widely distributed among ticks and wildlife in North America. Further molecular testing of sera from residents in areas where LB is endemic is warranted to enhance our understanding of the geographic distribution and frequency of occurrence of B. bissettii-like infections. PMID:21177909

  1. Invasion of the lyme disease vector Ixodes scapularis: implications for Borrelia burgdorferi endemicity.

    PubMed

    Hamer, Sarah A; Tsao, Jean I; Walker, Edward D; Hickling, Graham J

    2010-08-01

    Lyme disease risk is increasing in the United States due in part to the spread of blacklegged ticks Ixodes scapularis, the principal vector of the spirochetal pathogen Borrelia burgdorferi. A 5-year study was undertaken to investigate hypothesized coinvasion of I. scapularis and B. burgdorferi in Lower Michigan. We tracked the spatial and temporal dynamics of the tick and spirochete using mammal, bird, and vegetation drag sampling at eight field sites along coastal and inland transects originating in a zone of recent I. scapularis establishment. We document northward invasion of these ticks along Michigan's west coast during the study period; this pattern was most evident in ticks removed from rodents. B. burgdorferi infection prevalences in I. scapularis sampled from vegetation in the invasion zone were 9.3% and 36.6% in nymphs and adults, respectively, with the majority of infection (95.1%) found at the most endemic site. There was no evidence of I. scapularis invasion along the inland transect; however, low-prevalence B. burgdorferi infection was detected in other tick species and in wildlife at inland sites, and at northern coastal sites in years before the arrival of I. scapularis. These infections suggest that cryptic B. burgdorferi transmission by other vector-competent tick species is occurring in the absence of I. scapularis. Other Borrelia spirochetes, including those that group with B. miyamotoi and B. andersonii, were present at a low prevalence within invading ticks and local wildlife. Reports of Lyme disease have increased significantly in the invasion zone in recent years. This rapid blacklegged tick invasion--measurable within 5 years--in combination with cryptic pathogen maintenance suggests a complex ecology of Lyme disease emergence in which wildlife sentinels can provide an early warning of disease emergence.

  2. Role of small mammals in the ecology of Borrelia burgdorferi in a peri-urban park in north coastal California.

    PubMed

    Peavy, C A; Lane, R S; Kleinjan, J E

    1997-08-01

    The role of small mammals other than woodrats in the enzootiology of the Lyme disease spirochete, Borrelia burgorferi, was assessed in the peri-urban park. Mammals were collected monthly from September through to April. Following tick removal, the animals were tested for B. burgdorferi by culture of ear-punch biopsies. Larvae and nymphs that were intermediate in morphology between Ixodes spinipalpis and Ixodes neotomae occurred on several species of rodents (Peromyscus truei, Peromyscus californicus, Microtus californicus, Rattus rattus and Reithrodontomys megalotis) and the brush rabbit (Sylvilagus bachmani). Morphometric analyses of these I. spinipalpis-like ticks and the offspring from two I. neotomae females from the site suggest that I. neotomae may bo conspecific with I. spinipalpis. Borrelia burgdorferi was isolated from eight out of 109 (7.3%), three out of 16 (18.8%), two out of 38 (5.3%) and two out of six (33.3%) P. truei, P. maniculatus, M. californicus and R. rattus, respectively. One bush rabbit yielded the first isolate of B. burgdorferi from a lagomorph in western North America. This isolate and three others derived from unfed I. spinipalpis-like nymphs failed to produce infection when inoculated intradermally into 11-12 P. maniculatus each. Likewise, no spirochetes were detected in 420 Ixodes pacificus nymphs derived from larvae fed on animals inoculated with these isolates. An additional isolate, derived from an I. spinipalpis-like nymph, was recovered by ear-punch biopsies from five our of 12 (42%) needle-inoculated P. maniculatus. However, spirochetes were not detected in 20 I. pacificus nymphs fed as larvae on each of five mice (two infected and three uninfected) inoculated with this isolate. We conclude that brush rabbits and several species of rodents besides woodrats may contribute to the maintenance of B. burgdorferi because they harbour the spirochete and are fed upon by competent enzootic vectors. PMID:9291589

  3. Cyclic di-GMP modulates gene expression in Lyme disease spirochetes at the tick-mammal interface to promote spirochete survival during the blood meal and tick-to-mammal transmission.

    PubMed

    Caimano, Melissa J; Dunham-Ems, Star; Allard, Anna M; Cassera, Maria B; Kenedy, Melisha; Radolf, Justin D

    2015-08-01

    Borrelia burgdorferi, the Lyme disease spirochete, couples environmental sensing and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the contribution of these pathways to spirochete survival and gene regulation throughout the enzootic cycle. Live imaging of B. burgdorferi caught in the act of being acquired revealed that the absence of RpoS and the consequent derepression of tick-phase genes impart a Stay signal required for midgut colonization. In addition to the behavioral changes brought on by the RpoS-off state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by the Hk1/Rrp1 TCS; B. burgdorferi lacking either component is destroyed during the blood meal. Prior studies attributed this dramatic phenotype to a metabolic lesion stemming from reduced glycerol uptake and utilization. In a head-to-head comparison, however, the B. burgdorferi Δglp mutant had a markedly greater capacity to survive tick feeding than B. burgdorferi Δhk1 or Δrrp1 mutants, establishing unequivocally that glycerol metabolism is only one component of the protection afforded by c-di-GMP. Data presented herein suggest that the protective response mediated by c-di-GMP is multifactorial, involving chemotactic responses, utilization of alternate substrates for energy generation and intermediary metabolism, and remodeling of the cell envelope as a means of defending spirochetes against threats engendered during the blood meal. Expression profiling of c-di-GMP-regulated genes through the enzootic cycle supports our contention that the Hk1/Rrp1 TCS functions primarily, if not exclusively, in ticks. These data also raise the possibility that c-di-GMP enhances the expression of a subset of RpoS-dependent genes during nymphal transmission.

  4. Cyclic di-GMP Modulates Gene Expression in Lyme Disease Spirochetes at the Tick-Mammal Interface To Promote Spirochete Survival during the Blood Meal and Tick-to-Mammal Transmission

    PubMed Central

    Dunham-Ems, Star; Allard, Anna M.; Cassera, Maria B.; Kenedy, Melisha; Radolf, Justin D.

    2015-01-01

    Borrelia burgdorferi, the Lyme disease spirochete, couples environmental sensing and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the contribution of these pathways to spirochete survival and gene regulation throughout the enzootic cycle. Live imaging of B. burgdorferi caught in the act of being acquired revealed that the absence of RpoS and the consequent derepression of tick-phase genes impart a Stay signal required for midgut colonization. In addition to the behavioral changes brought on by the RpoS-off state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by the Hk1/Rrp1 TCS; B. burgdorferi lacking either component is destroyed during the blood meal. Prior studies attributed this dramatic phenotype to a metabolic lesion stemming from reduced glycerol uptake and utilization. In a head-to-head comparison, however, the B. burgdorferi Δglp mutant had a markedly greater capacity to survive tick feeding than B. burgdorferi Δhk1 or Δrrp1 mutants, establishing unequivocally that glycerol metabolism is only one component of the protection afforded by c-di-GMP. Data presented herein suggest that the protective response mediated by c-di-GMP is multifactorial, involving chemotactic responses, utilization of alternate substrates for energy generation and intermediary metabolism, and remodeling of the cell envelope as a means of defending spirochetes against threats engendered during the blood meal. Expression profiling of c-di-GMP-regulated genes through the enzootic cycle supports our contention that the Hk1/Rrp1 TCS functions primarily, if not exclusively, in ticks. These data also raise the possibility that c-di-GMP enhances the expression of a subset of RpoS-dependent genes during nymphal transmission. PMID:25987708

  5. Heterogeneity of Borrelia burgdorferi in the skin.

    PubMed

    Aberer, E; Kersten, A; Klade, H; Poitschek, C; Jurecka, W

    1996-12-01

    The reliability of various in vitro techniques to identify Borrelia burgdorferi infection is still unsatisfactory. Using a high-power resolution videomicroscope and staining with the borrelia genus-specific monoclonal flagellar antibody H9724, we identified borrelial structures in skin biopsies of erythema chronicum migrans (from which borrelia later was cultured), of acrodermatitis chronica atrophicans, and of morphea. In addition to typical borreliae, we noted stained structures of varying shapes identical to borreliae found in a "borrelia-injected skin" model; identical to agar-embedded borreliae; and identical to cultured borreliae following exposure to hyperimmune sera and/or antibiotics. We conclude that the H9724-reactive structures represent various forms of B. burgdorferi rather than staining artifacts. These "atypical" forms of B. burgdorferi may represent in vivo morphologic variants of this bacterium.

  6. Evidence that two ATP-dependent (Lon) proteases in Borrelia burgdorferi serve different functions.

    PubMed

    Coleman, James L; Katona, Laura I; Kuhlow, Christopher; Toledo, Alvaro; Okan, Nihal A; Tokarz, Rafal; Benach, Jorge L

    2009-11-01

    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 is upregulated transcriptionally by exposure to blood in vitro, while lon-2 is not. Because blood induction of Lon-1 may be of importance in the regulation of virulence factors critical for spirochete transmission, the clarification of functional roles for these two proteases in B. burgdorferi was the object of this study. On the chromosome, lon-2 is immediately downstream of ATP-dependent proteases clpP and clpX, an arrangement identical to that of lon of Escherichia coli. Phylogenetic analysis revealed that Lon-1 and Lon-2 cluster separately due to differences in the NH(2)-terminal substrate binding domains that may reflect differences in substrate specificity. Recombinant Lon-1 manifested properties of an ATP-dependent chaperone-protease in vitro but did not complement an E. coli Lon mutant, while Lon-2 corrected two characteristic Lon-mutant phenotypes. We conclude that B. burgdorferi Lons -1 and -2 have distinct functional roles. Lon-2 functions in a manner consistent with canonical Lon, engaged in cellular homeostasis. Lon-1, by virtue of its blood induction, and as a unique feature of the Borreliae, may be important in host adaptation from the arthropod to a warm-blooded host.

  7. Distribution, density, and Lyme disease spirochete infection in Ixodes dammini (Acari: Ixodidae) on white-tailed deer in Maryland.

    PubMed

    Amerasinghe, F P; Breisch, N L; Azad, A F; Gimpel, W F; Greco, M; Neidhardt, K; Pagac, B; Piesman, J; Sandt, J; Scott, T W

    1992-01-01

    A Statewide survey of ticks parasitizing white-tailed deer was carried out in Maryland during November 1989 to assess the status of the deer tick, Ixodes dammini Spielman, Clifford, Piesman & Corwin, the major vector of Lyme disease in the northeastern United States. Ticks were collected from deer carcasses brought in by hunters at 23 check stations (one per county). A total of 3,437 I. dammini were collected from 538 of 1,281 deer (42%), together with 2,013 Dermacentor albipictus (Packard) and 23 Amblyomma americanum (L.) from 34 and 0.5% of deer respectively. I. dammini prevalence ranged from 0 to 79% of deer and mean abundance from 0 to 7.3 ticks per deer at different check stations. Lyme spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, infection rates in ticks ranged from 0 to 21%, with a mean of 8%. Deer-tick density and spirochete infection rates varied with physiographic region and were low in the Appalachian, intermediate in the Piedmont, and high in the Western and Eastern Coastal Plains regions. County-based human case rates correlated positively with I. dammini abundance. We concluded that I. dammini was well established except in the mountainous western region of Maryland and was involved in Lyme disease transmission. PMID:1552529

  8. Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation.

    PubMed

    Iyer, Radha; Caimano, Melissa J; Luthra, Amit; Axline, David; Corona, Arianna; Iacobas, Dumitru A; Radolf, Justin D; Schwartz, Ira

    2015-02-01

    Borrelia burgdorferi, the agent of Lyme disease, is maintained in nature within an enzootic cycle involving a mammalian reservoir and an Ixodes sp. tick vector. The transmission, survival and pathogenic potential of B. burgdorferi depend on the bacterium's ability to modulate its transcriptome as it transits between vector and reservoir host. Herein, we employed an amplification-microarray approach to define the B. burgdorferi transcriptomes in fed larvae, fed nymphs and in mammalian host-adapted organisms cultivated in dialysis membrane chambers. The results show clearly that spirochetes exhibit unique expression profiles during each tick stage and during cultivation within the mammal; importantly, none of these profiles resembles that exhibited by in vitro grown organisms. Profound shifts in transcript levels were observed for genes encoding known or predicted lipoproteins as well as proteins involved in nutrient uptake, carbon utilization and lipid synthesis. Stage-specific expression patterns of chemotaxis-associated genes also were noted, suggesting that the composition and interactivities of the chemotaxis machinery components vary considerably in the feeding tick and mammal. The results as a whole make clear that environmental sensing by B. burgdorferi directly or indirectly drives an extensive and tightly integrated modulation of cell envelope constituents, chemotaxis/motility machinery, intermediary metabolism and cellular physiology. These findings provide the necessary transcriptional framework for delineating B. burgdorferi regulatory pathways throughout the enzootic cycle as well as defining the contribution(s) of individual genes to spirochete survival in nature and virulence in humans.

  9. Molecular identification of Salp15, a key salivary gland protein in the transmission of lyme disease spirochetes, from Ixodes persulcatus and Ixodes pacificus (Acari: Ixodidae).

    PubMed

    Hojgaard, Andrias; Biketov, Sergey F; Shtannikov, Alexander V; Zeidner, Nordin S; Piesman, Joseph

    2009-11-01

    Salp15 is a multifunctional protein, vital to the tick in its need to obtain vertebrate host blood without stimulating a host inflammatory and immune response. The Salpl5 protein from both Ixodes scapularis Say and Ixodes ricinus (L.), the principal vectors of the Lyme disease spirochete in eastern North America and Europe, respectively, have been well characterized and found to bind the murine CD4 receptor, DC-SIGN, and the OspC protein of Borrelia burgdorferi. In the current study, we characterized the full salp15 gene in Ixodes pacificus Cooley & Kohls and Ixodes persulcatus Schulze, the principal vectors of Lyme disease spirochetes in western North America and Asia, respectively. In comparing the Salp15 protein of all four principal vector ticks of public health importance for the transmission of Lyme disease spirochetes, we find the 53 C-terminal amino acids to have a high degree of similarity. There are at least three clades in the tree of Salp15 and its homologues, probably representing a multigene family.

  10. Why are there several species of Borrelia burgdorferi sensu lato detected in dogs and humans?

    PubMed

    Skotarczak, Bogumiła

    2014-04-01

    Borrelia burgdorferi sensu lato is a group of spirochete bacteria species some of which cause borreliosis in humans and dogs. Humans and dogs are susceptible to illness from many of the same tick-borne pathogens, including B. burgdorferi s.l. (Bbsl). Little is known about the pathogenic role of the species of Bbsl in canines. The molecular methods which detect and amplify the DNA of borreliae and allow differentiating borreliae species or strains have not been used in canine diagnostics yet. Until now, it has been believed that in European dogs, like in humans, at least three pathogenic species occur but the most frequently described symptoms may be associated with the infection caused by B. burgdorferi sensu stricto species. A dog as well as a human is a host for many species of Bbsl, because borreliacidal ability of serum of dogs and humans is evident only in certain genospecies of Bbsl. Therefore both a dog and a human harbor more species than in case of some wild animal species which create older phylogenetic Bbsl species-host systems and these animals may act even as a non-competent reservoir host. Apart from many genospecies of Bbsl, a dog harbors other tick-borne agents and dual or triple infections may occur.

  11. Initial characterization of the FlgE hook high molecular weight complex of Borrelia burgdorferi.

    PubMed

    Miller, Kelly A; Motaleb, Md A; Liu, Jun; Hu, Bo; Caimano, Melissa J; Miller, Michael R; Charon, Nyles W

    2014-01-01

    The spirochete periplasmic flagellum has many unique attributes. One unusual characteristic is the flagellar hook. This structure serves as a universal joint coupling rotation of the membrane-bound motor to the flagellar filament. The hook is comprised of about 120 FlgE monomers, and in most bacteria these structures readily dissociate to monomers (∼ 50 kDa) when treated with heat and detergent. However, in spirochetes the FlgE monomers form a large mass of over 250 kDa [referred to as a high molecular weight complex (HMWC)] that is stable to these and other denaturing conditions. In this communication, we examined specific aspects with respect to the formation and structure of this complex. We found that the Lyme disease spirochete Borrelia burgdorferi synthesized the HMWC throughout the in vitro growth cycle, and also in vivo when implanted in dialysis membrane chambers in rats. The HMWC was stable to formic acid, which supports the concept that the stability of the HMWC is dependent on covalent cross-linking of individual FlgE subunits. Mass spectrometry analysis of the HMWC from both wild type periplasmic flagella and polyhooks from a newly constructed ΔfliK mutant indicated that other proteins besides FlgE were not covalently joined to the complex, and that FlgE was the sole component of the complex. In addition, mass spectrometry analysis also indicated that the HMWC was composed of a polymer of the FlgE protein with both the N- and C-terminal regions remaining intact. These initial studies set the stage for a detailed characterization of the HMWC. Covalent cross-linking of FlgE with the accompanying formation of the HMWC we propose strengthens the hook structure for optimal spirochete motility. PMID:24859001

  12. Role of Fc Gamma Receptors in Triggering Host Cell Activation and Cytokine Release by Borrelia burgdorferi

    PubMed Central

    Talkington, Jeffrey; Nickell, Steven P.

    2001-01-01

    Borrelia burgdorferi, the spirochetal bacterium that causes human Lyme disease, encodes numerous lipoproteins which have the capacity to trigger the release of proinflammatory cytokines from a variety of host cell types, and it is generally believed that these cytokines contribute to the disease process in vivo. We previously reported that low-passage-number infectious B. burgdorferi spirochetes express a novel lipidation-independent activity which induces secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) by the mouse MC/9 mast cell line. Using RNase protection assays, we determined that mast cells exposed in vitro to low-passage-number, but not high-passage-number, B. burgdorferi spirochetes show increased expression of additional mRNAs representing several chemokines, including macrophage-inflammatory protein 1α (MIP-1α), MIP-1β, and TCA3, as well as the proinflammatory cytokine interleukin-6. Furthermore, mast cell TNF-α secretion can be inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin and also by preincubation with purified mouse immunoglobulin G1 (IgG1) and IgG2a, but not mouse IgG3, and by a mouse Fc gamma receptor II and III (FcγRII/III)-specific rat monoclonal antibody, suggesting the likely involvement of host FcγRIII in B. burgdorferi-mediated signaling. A role for passively adsorbed rabbit or bovine IgG or serum components in B. burgdorferi-mediated FcγR signaling was excluded in control experiments. These studies confirm that low-passage-number B. burgdorferi spirochetes express a novel activity which upregulates the expression of a variety of host cell chemokine and cytokine genes, and they also establish a novel antibody-independent role for FcγRs in transduction of activation signals by bacterial products. PMID:11119532

  13. Oral Immunization with OspC Does Not Prevent Tick-Borne Borrelia burgdorferi Infection

    PubMed Central

    Melo, Rita; Richer, Luciana; Johnson, Daniel L.; Gomes-Solecki, Maria

    2016-01-01

    Oral vaccination strategies are of interest to prevent transmission of Lyme disease as they can be used to deliver vaccines to humans, pets, and to natural wildlife reservoir hosts of Borrelia burgdorferi. We developed a number of oral vaccines based in E. coli expressing recombinant OspC type K, OspB, BBK32 from B. burgdorferi, and Salp25, Salp15 from Ixodes scapularis. Of the five immunogenic candidates only OspC induced significant levels of antigen-specific IgG and IgA when administered to mice via the oral route. Antibodies to OspC did not prevent dissemination of B. burgdorferi as determined by the presence of spirochetes in ear, heart and bladder tissues four weeks after challenge. Next generation sequencing of genomic DNA from ticks identified multiple phyletic types of B. burgdorferi OspC (A, D, E, F, I, J, K, M, Q, T, X) in nymphs that engorged on vaccinated mice. PCR amplification of OspC types A and K from flat and engorged nymphal ticks, and from heart and bladder tissues collected after challenge confirmed sequencing analysis. Quantification of spirochete growth in a borreliacidal assay shows that both types of spirochetes (A and K) survived in the presence of OspC-K specific serum whereas the spirochetes were killed by OspA specific serum. We show that oral vaccination of C3H-HeN mice with OspC-K induced significant levels of antigen-specific IgG. However, these serologic antibodies did not protect mice from infection with B. burgdorferi expressing homologous or heterologous types of OspC after tick challenge. PMID:26990760

  14. Initial characterization of the FlgE hook high molecular weight complex of Borrelia burgdorferi.

    PubMed

    Miller, Kelly A; Motaleb, Md A; Liu, Jun; Hu, Bo; Caimano, Melissa J; Miller, Michael R; Charon, Nyles W

    2014-01-01

    The spirochete periplasmic flagellum has many unique attributes. One unusual characteristic is the flagellar hook. This structure serves as a universal joint coupling rotation of the membrane-bound motor to the flagellar filament. The hook is comprised of about 120 FlgE monomers, and in most bacteria these structures readily dissociate to monomers (∼ 50 kDa) when treated with heat and detergent. However, in spirochetes the FlgE monomers form a large mass of over 250 kDa [referred to as a high molecular weight complex (HMWC)] that is stable to these and other denaturing conditions. In this communication, we examined specific aspects with respect to the formation and structure of this complex. We found that the Lyme disease spirochete Borrelia burgdorferi synthesized the HMWC throughout the in vitro growth cycle, and also in vivo when implanted in dialysis membrane chambers in rats. The HMWC was stable to formic acid, which supports the concept that the stability of the HMWC is dependent on covalent cross-linking of individual FlgE subunits. Mass spectrometry analysis of the HMWC from both wild type periplasmic flagella and polyhooks from a newly constructed ΔfliK mutant indicated that other proteins besides FlgE were not covalently joined to the complex, and that FlgE was the sole component of the complex. In addition, mass spectrometry analysis also indicated that the HMWC was composed of a polymer of the FlgE protein with both the N- and C-terminal regions remaining intact. These initial studies set the stage for a detailed characterization of the HMWC. Covalent cross-linking of FlgE with the accompanying formation of the HMWC we propose strengthens the hook structure for optimal spirochete motility.

  15. Borrelia burgdorferi Harbors a Transport System Essential for Purine Salvage and Mammalian Infection

    PubMed Central

    Jain, Sunny; Sutchu, Selina; Rosa, Patricia A.; Byram, Rebecca

    2012-01-01

    Borrelia burgdorferi is the tick-borne bacterium that causes the multistage inflammatory disease Lyme disease. B. burgdorferi has a reduced genome and lacks the enzymes required for de novo synthesis of purines for synthesis of RNA and DNA. Therefore, this obligate pathogen is dependent upon the tick vector and mammalian host environments for salvage of purine bases for nucleic acid biosynthesis. This pathway is vital for B. burgdorferi survival throughout its infectious cycle, as key enzymes in the purine salvage pathway are essential for the ability of the spirochete to infect mice and critical for spirochete replication in the tick. The transport of preformed purines into the spirochete is the first step in the purine salvage pathway and may represent a novel therapeutic target and/or means to deliver antispirochete molecules to the pathogen. However, the transport systems critical for purine salvage by B. burgdorferi have yet to be identified. Herein, we demonstrate that the genes bbb22 and bbb23, present on B. burgdorferi's essential plasmid circular plasmid 26 (cp26), encode key purine transport proteins. BBB22 and/or BBB23 is essential for hypoxanthine transport and contributes to the transport of adenine and guanine. Furthermore, B. burgdorferi lacking bbb22-23 was noninfectious in mice up to a dose of 1 × 107 spirochetes. Together, our data establish that bbb22-23 encode purine permeases critical for B. burgdorferi mammalian infectivity, suggesting that this transport system may serve as a novel antimicrobial target for the treatment of Lyme disease. PMID:22710875

  16. Differential Expression of Borrelia burgdorferi Proteins during Growth In Vitro

    PubMed Central

    Ramamoorthy, Ramesh; Philipp, Mario T.

    1998-01-01

    In an earlier paper we described the transcriptionally regulated differential levels of expression of two lipoproteins of Borrelia burgdorferi, P35 and P7.5, during growth of the spirochetes in culture from logarithmic phase to stationary phase (K. J. Indest, R. Ramamoorthy, M. Solé, R. D. Gilmore, B. J. B. Johnson, and M. T. Philipp, Infect. Immun. 65:1165–1171, 1997). Here we further assess this phenomenon by investigating whether the expression of other antigens of B. burgdorferi, including some well-characterized ones, are also regulated in a growth-phase-dependent manner in vitro. These studies revealed 13 additional antigens, including OspC, BmpD, and GroEL, that were upregulated 2- to 66-fold and a 28-kDa protein that was downregulated 2- to 10-fold, during the interval between the logarithmic- and stationary-growth phases. Unlike with these in vitro-regulated proteins, the levels of expression of OspA, OspB, P72, flagellin, and BmpA remained unchanged throughout growth of the spirochetes in culture. Furthermore, ospAB, bmpAB, groEL, and fla all exhibited similar mRNA profiles, which is consistent with the constitutive expression of these genes. By contrast, the mRNA and protein profiles of ospC and bmpD indicated regulated expression of these genes. While bmpD exhibited a spike in mRNA expression in early stationary phase, ospC maintained a relatively higher level of mRNA throughout culture. These findings demonstrate that there are additional genes besides P7.5 and P35 whose regulated expression can be investigated in vitro and which may thus serve as models to facilitate the study of regulatory mechanisms in an organism that cycles between an arthropod and a vertebrate host. PMID:9784512

  17. Borrelia burgdorferi Infections in the United States

    PubMed Central

    Heymann, Warren R.

    2012-01-01

    It is becoming increasingly evident that the clinical presentation of infection with Borrelia burgdorferi varies greatly between different parts of the world. A growing number of European and Asian isolates of Lyme borreliae, differing from the American strain of Borrelia burgdorferi, have been identified in several different disorders. In light of the increasing number of reports describing an association between various cutaneous disorders and infection with Borrelia burgdorferi and the controversy that still remains over where Borrelia burgdorferi is truly pathogenic in these diseases, this review of the literature assesses the significance of these reports in substantiating these hypotheses, as such associations are important both diagnostically and therapeutically. PMID:22916311

  18. Immunohistochemical and ultrastructural detection of intestinal spirochetes in Thoroughbred horses.

    PubMed

    Shibahara, Tomoyuki; Kuwano, Atsutoshi; Ueno, Takanori; Katayama, Yoshinari; Ohya, Tatsuo; Taharaguchi, Sadao; Yamamoto, Shinji; Umemura, Takashi; Ishikawa, Yoshiharu; Kadota, Koichi

    2005-03-01

    Studies of equine intestinal spirochetes have long focused on intestinal contents alone, but intestinal spirochetosis has been reported recently in a 21-month-old Thoroughbred colt in Japan. To define the clinical and pathological significances of intestinal spirochetosis in several horses, an epizootiologic survey with histologic, immunohistochemical, and ultrastructural methods was conducted for Brachyspira antigen-containing intestinal spirochetes in 12 diseased or injured Thoroughbred horses, aged from 35 days to 17 years. Brachyspira antigen-containing spirochetes were found in 7 of 12 horses (58.3%) and were more frequent in the cecum than in other parts of the bowel. It was not clear whether the infection was clinically related to diarrhea or dysentery, but histopathology revealed a close association between the bacterial infection and epithelial hyperplasia. Crypt epithelium consisted mainly of goblet cells and showed frequent mitosis throughout its length. Inflammatory cells and congestion were also present. There were numerous spirochetes in the crypts, and some invaded the cecal and colonic epithelia and underlying lamina propria. Ultrastructurally, the spirochetes were divided into 4 types. Three types were identified in degenerative epithelial cells or intracellularly. Brachyspira antigen-containing intestinal spirochetes invading the mucosa were capable of causing epithelial hyperplasia in the cecum and colon in the horses. The findings in this study will increase awareness of the importance of intestinal spirochetosis and may also be helpful for diagnosis and treatment of this condition. PMID:15825495

  19. Borrelia burgdorferi upregulates the adhesion molecules E-selectin, P-selectin, ICAM-1 and VCAM-1 on mouse endothelioma cells in vitro.

    PubMed

    Böggemeyer, E; Stehle, T; Schaible, U E; Hahne, M; Vestweber, D; Simon, M M

    1994-06-01

    In order to obtain more information on processes leading to Borrelia burgdorferi-induced inflammation in the host, we have developed an in vitro model to study the upregulation of cell surface expression of adhesion molecules on endothelial cells by spirochetes. A mouse endothelioma cell line, derived from brain capillaries, bEnd3, was used as indicator population. bEnd3 cells were incubated with preparations of viable, inactivated or sonicated spirochetes and the expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 was monitored by immunocytochemistry and quantified by cell surface ELISA. We show that all three spirochetal preparations are able to upregulate cell surface expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 on bEnd 3 cells in a dose-dependent manner. The kinetics of cell surface expression of the individual adhesion molecules in the presence of Borrelia burgdorferi showed maxima at about 50 h of incubation or later; this was distinct from results obtained with sonicated-preparations of Escherichia coli bacteria or with enterobacterial LPS where peak expression was observed between 4 h and 16 h. The fact that Borrelia burgdorferi does not contain conventional LPS suggests that the mode of induction of adhesion molecules on endothelial cells is influenced by the phenotype of bacteria. At the peak of spirochete-induced cell surface expression of adhesion molecules (approximately 50 h), bEnd3 cells were found to bind cells of a VLA-4+ B lymphoma line (L1-2) much more efficiently than untreated control cells. The binding of L1-2 cells to presensitized bEnd3 cells was significantly inhibited (more than 75%) in the presence of monoclonal antibodies to both VLA-4 and its endothelial counterreceptor VCAM-1. These findings demonstrate that Borrelia burgdorferi organisms are able to induce functionally active adhesion molecules on endothelial cells in vitro and suggest that E-selectin, P-selectin, ICAM-1 and VCAM-1 play an important role in the

  20. Borrelia burgdorferi upregulates the adhesion molecules E-selectin, P-selectin, ICAM-1 and VCAM-1 on mouse endothelioma cells in vitro.

    PubMed

    Böggemeyer, E; Stehle, T; Schaible, U E; Hahne, M; Vestweber, D; Simon, M M

    1994-06-01

    In order to obtain more information on processes leading to Borrelia burgdorferi-induced inflammation in the host, we have developed an in vitro model to study the upregulation of cell surface expression of adhesion molecules on endothelial cells by spirochetes. A mouse endothelioma cell line, derived from brain capillaries, bEnd3, was used as indicator population. bEnd3 cells were incubated with preparations of viable, inactivated or sonicated spirochetes and the expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 was monitored by immunocytochemistry and quantified by cell surface ELISA. We show that all three spirochetal preparations are able to upregulate cell surface expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 on bEnd 3 cells in a dose-dependent manner. The kinetics of cell surface expression of the individual adhesion molecules in the presence of Borrelia burgdorferi showed maxima at about 50 h of incubation or later; this was distinct from results obtained with sonicated-preparations of Escherichia coli bacteria or with enterobacterial LPS where peak expression was observed between 4 h and 16 h. The fact that Borrelia burgdorferi does not contain conventional LPS suggests that the mode of induction of adhesion molecules on endothelial cells is influenced by the phenotype of bacteria. At the peak of spirochete-induced cell surface expression of adhesion molecules (approximately 50 h), bEnd3 cells were found to bind cells of a VLA-4+ B lymphoma line (L1-2) much more efficiently than untreated control cells. The binding of L1-2 cells to presensitized bEnd3 cells was significantly inhibited (more than 75%) in the presence of monoclonal antibodies to both VLA-4 and its endothelial counterreceptor VCAM-1. These findings demonstrate that Borrelia burgdorferi organisms are able to induce functionally active adhesion molecules on endothelial cells in vitro and suggest that E-selectin, P-selectin, ICAM-1 and VCAM-1 play an important role in the

  1. Yellow Fever

    MedlinePlus

    ... tropical and subtropical areas in South America and Africa. The virus is transmitted to people by the ... fever Maps of Yellow fever endemic areas in Africa and South America Yellow fever vaccination Prevention Vaccine ...

  2. Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages

    PubMed Central

    Carrasco, Sebastian E.; Troxell, Bryan; Yang, Youyun; Brandt, Stephanie L.; Li, Hongxia; Sandusky, George E.; Condon, Keith W.

    2015-01-01

    Outer surface protein C (OspC) is one of the major lipoproteins expressed on the surface of Borrelia burgdorferi during tick feeding and the early phase of mammalian infection. OspC is required for B. burgdorferi to establish infection in both immunocompetent and SCID mice and has been proposed to facilitate evasion of innate immune defenses. However, the exact biological function of OspC remains elusive. In this study, we showed that the ospC-deficient spirochete could not establish infection in NOD-scid IL2rγnull mice that lack B cells, T cells, NK cells, and lytic complement. The ospC mutant also could not establish infection in anti-Ly6G-treated SCID and C3H/HeN mice (depletion of neutrophils). However, depletion of mononuclear phagocytes at the skin site of inoculation in SCID and C3H/HeN mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted mice, the ospC mutant was able to colonize the joints and triggered neutrophilia during dissemination. Furthermore, we found that phagocytosis of green fluorescent protein (GFP)-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 macrophage-like cells, but not in PMN-HL60, was significantly higher than parental wild-type B. burgdorferi strains, suggesting that OspC has an antiphagocytic property. In addition, overproduction of OspC in spirochetes also decreased the uptake of spirochetes by murine peritoneal macrophages. Together, our findings provide evidence that mononuclear phagocytes play a key role in clearance of the ospC mutant and that OspC promotes spirochetes' evasion of macrophages during early Lyme borreliosis. PMID:26438793

  3. Borrelia, Rickettsia, and Ehrlichia species in bat ticks, France, 2010.

    PubMed

    Socolovschi, Cristina; Kernif, Tahar; Raoult, Didier; Parola, Philippe

    2012-12-01

    Argas vespertilionis, an argasid tick associated with bats and bat habitats in Europe, Africa, and Asia has been reported to bite humans; however, studies investigating the presence of vector-borne pathogens in these ticks are lacking. Using molecular tools, we tested 5 A. vespertilionis ticks collected in 2010 from the floor of a bat-infested attic in southwestern France that had been converted into bedrooms. Rickettsia sp. AvBat, a new genotype of spotted fever group rickettsiae, was detected and cultivated from 3 of the 5 ticks. A new species of the Ehrlichia canis group, Ehrlichia sp. AvBat, was also detected in 3 ticks. Four ticks were infected with Borrelia sp. CPB1, a relapsing fever agent of the Borrelia group that caused fatal borreliosis in a bat in the United Kingdom. Further studies are needed to characterize these new agents and determine if the A. vespertilionis tick is a vector and/or reservoir of these agents. PMID:23171714

  4. Borrelia, Rickettsia, and Ehrlichia Species in Bat Ticks, France, 2010

    PubMed Central

    Socolovschi, Cristina; Kernif, Tahar; Raoult, Didier

    2012-01-01

    Argas vespertilionis, an argasid tick associated with bats and bat habitats in Europe, Africa, and Asia has been reported to bite humans; however, studies investigating the presence of vector-borne pathogens in these ticks are lacking. Using molecular tools, we tested 5 A. vespertilionis ticks collected in 2010 from the floor of a bat-infested attic in southwestern France that had been converted into bedrooms. Rickettsia sp. AvBat, a new genotype of spotted fever group rickettsiae, was detected and cultivated from 3 of the 5 ticks. A new species of the Ehrlichia canis group, Ehrlichia sp. AvBat, was also detected in 3 ticks. Four ticks were infected with Borrelia sp. CPB1, a relapsing fever agent of the Borrelia group that caused fatal borreliosis in a bat in the United Kingdom. Further studies are needed to characterize these new agents and determine if the A. vespertilionis tick is a vector and/or reservoir of these agents. PMID:23171714

  5. Asymptomatic infection with Borrelia burgdorferi.

    PubMed

    Steere, Allen C; Sikand, Vijay K; Schoen, Robert T; Nowakowski, John

    2003-08-15

    The natural history of asymptomatic seroconversion to Borrelia burgdorferi has been unclear. We report here, on the basis of a post hoc assessment, the frequency and outcome of asymptomatic seroconversion to B. burgdorferi in participants of a large Lyme disease vaccine trial. We show that infection with B. burgdorferi may be asymptomatic but that asymptomatic infection is unusual in the United States.

  6. Recombinant constructs of Borrelia burgdorferi

    DOEpatents

    Dattwyler, Raymond J.; Gomes-Solecki, Maria J. C.; Luft, Benjamin J.; Dunn, John J.

    2007-02-20

    Novel chimeric nucleic acids, encoding chimeric Borrelia proteins comprising OspC or an antigenic fragment thereof and OspA or an antigenic fragment thereof, are disclosed. Chimeric proteins encoded by the nucleic acid sequences are also disclosed. The chimeric proteins are useful as vaccine immunogens against Lyme borreliosis, as well as for immunodiagnostic reagents.

  7. Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro.

    PubMed

    Theophilus, P A S; Victoria, M J; Socarras, K M; Filush, K R; Gupta, K; Luecke, D F; Sapi, E

    2015-12-01

    Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treatment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains unknown, but recent studies suggested the possibilities of the presence of antibiotic resistant Borrelia persister cells and biofilms. In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferi spirochetes, persisters, and biofilm forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to different microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combinations. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters. Subculture experiments with Stevia and antibiotics treated cells were established for 7 and 14 days yielding, no and 10% viable cells, respectively compared to the above-mentioned antibiotics and antibiotic combination. When Stevia and the three antibiotics were tested against attached biofilms, Stevia significantly reduced B. burgdorferi forms. Results from this study suggest that a natural product such as Stevia leaf extract could be considered as an effective agent against B. burgdorferi. PMID:26716015

  8. Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro.

    PubMed

    Theophilus, P A S; Victoria, M J; Socarras, K M; Filush, K R; Gupta, K; Luecke, D F; Sapi, E

    2015-12-01

    Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treatment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains unknown, but recent studies suggested the possibilities of the presence of antibiotic resistant Borrelia persister cells and biofilms. In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferi spirochetes, persisters, and biofilm forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to different microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combinations. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters. Subculture experiments with Stevia and antibiotics treated cells were established for 7 and 14 days yielding, no and 10% viable cells, respectively compared to the above-mentioned antibiotics and antibiotic combination. When Stevia and the three antibiotics were tested against attached biofilms, Stevia significantly reduced B. burgdorferi forms. Results from this study suggest that a natural product such as Stevia leaf extract could be considered as an effective agent against B. burgdorferi.

  9. Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro

    PubMed Central

    Theophilus, P. A. S.; Victoria, M. J.; Socarras, K. M.; Filush, K. R.; Gupta, K.; Luecke, D. F.; Sapi, E.

    2015-01-01

    Lyme disease is a tick-borne multisystemic disease caused by Borrelia burgdorferi. Administering antibiotics is the primary treatment for this disease; however, relapse often occurs when antibiotic treatment is discontinued. The reason for relapse remains unknown, but recent studies suggested the possibilities of the presence of antibiotic resistant Borrelia persister cells and biofilms. In this study, we evaluated the effectiveness of whole leaf Stevia extract against B. burgdorferi spirochetes, persisters, and biofilm forms in vitro. The susceptibility of the different forms was evaluated by various quantitative techniques in addition to different microscopy methods. The effectiveness of Stevia was compared to doxycycline, cefoperazone, daptomycin, and their combinations. Our results demonstrated that Stevia had significant effect in eliminating B. burgdorferi spirochetes and persisters. Subculture experiments with Stevia and antibiotics treated cells were established for 7 and 14 days yielding, no and 10% viable cells, respectively compared to the above-mentioned antibiotics and antibiotic combination. When Stevia and the three antibiotics were tested against attached biofilms, Stevia significantly reduced B. burgdorferi forms. Results from this study suggest that a natural product such as Stevia leaf extract could be considered as an effective agent against B. burgdorferi. PMID:26716015

  10. Coordinate synthesis and turnover of heat shock proteins in Borrelia burgdorferi: degradation of DnaK during recovery from heat shock.

    PubMed Central

    Cluss, R G; Goel, A S; Rehm, H L; Schoenecker, J G; Boothby, J T

    1996-01-01

    The synthesis and turnover of heat shock proteins (Hsps) by Borrelia burgdorferi, the Lyme disease spirochete, was investigated by radiolabeling of whole spirochetes and spheroplasts, comparison of one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and use of immunochemistry. The approximately 72-kDa DnaK homolog and three additional Hsps of 39, 27, and 21 kDa increased in amount by 3- to 15-fold between 2 and 6 h following temperature upshift from 28 to 39 degrees C. Temperature downshift experiments following the transfer of spirochetes from 40 to 28 degrees C showed that within 15 to 30 min, synthesis of most of the major Hsps returned to levels seen in spirochetes statically maintained at the lower temperature. Spheroplasts of B. burgdorferi produced by treatment with EDTA and lysozyme were radiolabeled, and specific Hsps were localized to either the cytoplasm or membrane fraction. Further analysis by two-dimensional electrophoresis demonstrated three constitutively expressed DnaK isoforms with pIs near 5.5. A pattern suggestive of DnaK degradation was observed following recovery from heat shock but not in spirochetes maintained entirely at a low temperature. Some of these putative degradation products were recognized by monoclonal antibodies directed against the B. burgdorferi DnaK protein. These data suggest that following a period of peak synthesis, DnaK is actively degraded as the spirochete reestablishes its metabolic thermometer. These findings provide a new interpretation of previous work suggesting that 10 to 15 B. burgdorferi polypeptides, including DnaK have a common epitope. PMID:8613385

  11. Virulent strain associated outer membrane proteins of Borrelia burgdorferi.

    PubMed Central

    Skare, J T; Shang, E S; Foley, D M; Blanco, D R; Champion, C I; Mirzabekov, T; Sokolov, Y; Kagan, B L; Miller, J N; Lovett, M A

    1995-01-01

    We have isolated and purified outer membrane vesicles (OMV) from Borrelia burgdorferi strain B31 based on methods developed for isolation of Treponema pallidum OMV. Purified OMV exhibited distinct porin activities with conductances of 0.6 and 12.6 nano-Siemen and had no detectable beta-NADH oxidase activity indicating their outer membrane origin and their lack of inner membrane contamination, respectively. Hydrophobic proteins were identified by phase partitioning with Triton X-114. Most of these hydrophobic membrane proteins were not acylated, suggesting that they are outer membrane-spanning proteins. Identification of palmitate-labeled lipoproteins revealed that several were enriched in the OMV, several were enriched in the protoplasmic cylinder inner membrane fraction, and others were found exclusively associated with the inner membrane. The protein composition of OMV changed significantly with successive in vitro cultivation of strain B31. Using antiserum with specificity for virulent strain B31, we identified OMV antigens on the surface of the spirochete and identified proteins whose presence in OMV could be correlated with virulence and protective immunity in the rabbit Lyme disease model. These virulent strain associated outer membrane-spanning proteins may provide new insight into the pathogenesis of Lyme disease. Images PMID:7593626

  12. Proteome Analysis of Borrelia burgdorferi Response to Environmental Change

    SciTech Connect

    Angel, Thomas E.; Luft, Benjamin J.; Yang, Xiaohua; Nicora, Carrie D.; Camp, David G.; Jacobs, Jon M.; Smith, Richard D.

    2010-11-02

    We examined global changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to two environmental cues (pH and temperature) chosen for their reported similarity to those encountered at different stages of the organism’s life cycle. Multidimensional nano-liquid chromatographic separations coupled with tandem mass spectrometry were used to examine the array of proteins (i.e., the proteome) of B. burgdorferi for different pH and temperature culture conditions. Changes in pH and temperature elicited in vitro adaptations of this spirochete known to cause Lyme disease and led to alterations in protein expression that are associated with increased microbial pathogenesis. We identified 1031 proteins that represent 59% of the annotated genome of B. burgdorferi and elucidated a core proteome of 414 proteins that were present in all environmental conditions investigated. Observed changes in protein abundances indicated varied replicon usage, as well as proteome functional distributions between the in vitro cell culture conditions. Surprisingly, the pH and temperature conditions that mimicked B. burgdorferi residing in the gut of a fed tick showed a marked reduction in protein diversity. Additionally, the results provide us with leading candidates for exploring how B. burgdorferi adapts to and is able to survive in a wide variety of environmental conditions and lay a foundation for planned in situ studies of B. burgdorferi isolated from the tick midgut and infected animals.

  13. Distribution of Borrelia burgdorferi in host mice in Pennsylvania.

    PubMed Central

    Lord, R D; Lord, V R; Humphreys, J G; McLean, R G

    1994-01-01

    Host mice (Peromyscus leucopus and Peromyscus maniculatus) were sampled throughout the state of Pennsylvania to determine the geographical and ecological distribution of the Lyme disease spirochete Borrelia burgdorferi. All 67 counties of the state were sampled. A total of 1,619 mice were captured from a total of 157 sites during the period 1990 to 1993 for an overall capture rate of 29.69%. A total of 112 (6.92%) isolations of B. burgdorferi were made. The distribution of isolations revealed the reason for the correlated distribution of human cases of Lyme disease in the state. Significantly more mice were captured and significantly more isolations were made from hemlock (Tsuga canadensis) habitat than from deciduous species forest. Nevertheless, high isolation rates from counties of the southeastern corner of the state illustrate well that hemlock habitat is not essential. Evidence suggests that in some areas, transmission between mice is occurring in some way other than through ticks as vectors. Host mice proved useful for determining the geographical and ecological distribution of B. burgdorferi. PMID:7814489

  14. Distribution of Borrelia burgdorferi in host mice in Pennsylvania.

    PubMed

    Lord, R D; Lord, V R; Humphreys, J G; McLean, R G

    1994-10-01

    Host mice (Peromyscus leucopus and Peromyscus maniculatus) were sampled throughout the state of Pennsylvania to determine the geographical and ecological distribution of the Lyme disease spirochete Borrelia burgdorferi. All 67 counties of the state were sampled. A total of 1,619 mice were captured from a total of 157 sites during the period 1990 to 1993 for an overall capture rate of 29.69%. A total of 112 (6.92%) isolations of B. burgdorferi were made. The distribution of isolations revealed the reason for the correlated distribution of human cases of Lyme disease in the state. Significantly more mice were captured and significantly more isolations were made from hemlock (Tsuga canadensis) habitat than from deciduous species forest. Nevertheless, high isolation rates from counties of the southeastern corner of the state illustrate well that hemlock habitat is not essential. Evidence suggests that in some areas, transmission between mice is occurring in some way other than through ticks as vectors. Host mice proved useful for determining the geographical and ecological distribution of B. burgdorferi.

  15. The western fence lizard Sceloporus occidentalis: evidence of field exposure to Borrelia burgdorferi in relation to infestation by Ixodes pacificus (Acari: Ixodidae).

    PubMed

    Manweiler, S A; Lane, R S; Tempelis, C H

    1992-09-01

    The role of the Western fence lizard Sceloporus occidentalis in the enzootiology of the Lyme disease spirochete Borrelia burgdorferi was evaluated in the Hopland and Ukiah areas of Mendocino County, California. In 1989, half of 74 lizards collected monthly from April to October at Hopland were infested by the immature western black-legged tick Ixodes pacificus at a mean intensity of 6.0 ticks per lizard. The prevalence of infestation of lizards by immature I. pacificus (36 of 73) at Ukiah was similar, but the mean intensity (12.9) was approximately twice as great. Overall, zero of 223 larvae and 2 (0.6%) of 330 nymphs from both sites were found to contain spirochetes by direct immunofluorescence. Larval and nymphal I. pacificus fit the negative binomial distribution in spring, and the prevalence and abundance of these stages were significantly greater in spring than in summer at both sites. Spirochetes were not visualized in thick blood films prepared from 133 lizards from both localities. Plasma antibodies against B. burgdorferi were detected in seven of 10 experimentally inoculated lizards, in five (8%) of 63 lizards from Hopland, and in 10 (14%) of 70 lizards from Ukiah. Adult lizards had a significantly greater tick burden and seropositivity rate than juvenile lizards only at Ukiah. In 1991, efforts to detect and culture spirochetes from the blood of 21 wild-caught lizards and from the tissues of 189 associated ticks that fed xenodiagnostically on them were unsuccessful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1524146

  16. Motor Rotation Is Essential for the Formation of the Periplasmic Flagellar Ribbon, Cellular Morphology, and Borrelia burgdorferi Persistence within Ixodes scapularis Tick and Murine Hosts

    PubMed Central

    Sultan, Syed Z.; Sekar, Padmapriya; Zhao, Xiaowei; Manne, Akarsh; Liu, Jun; Wooten, R. Mark

    2015-01-01

    Borrelia burgdorferi must migrate within and between its arthropod and mammalian hosts in order to complete its natural enzootic cycle. During tick feeding, the spirochete transmits from the tick to the host dermis, eventually colonizing and persisting within multiple, distant tissues. This dissemination modality suggests that flagellar motor rotation and, by extension, motility are crucial for infection. We recently reported that a nonmotile flaB mutant that lacks periplasmic flagella is rod shaped and unable to infect mice by needle or tick bite. However, those studies could not differentiate whether motor rotation or merely the possession of the periplasmic flagella was crucial for cellular morphology and host persistence. Here, we constructed and characterized a motB mutant that is nonmotile but retains its periplasmic flagella. Even though ΔmotB bacteria assembled flagella, part of the mutant cell is rod shaped. Cryoelectron tomography revealed that the flagellar ribbons are distorted in the mutant cells, indicating that motor rotation is essential for spirochetal flat-wave morphology. The ΔmotB cells are unable to infect mice, survive in the vector, or migrate out of the tick. Coinfection studies determined that the presence of these nonmotile ΔmotB cells has no effect on the clearance of wild-type spirochetes during murine infection and vice versa. Together, our data demonstrate that while flagellar motor rotation is necessary for spirochetal morphology and motility, the periplasmic flagella display no additional properties related to immune clearance and persistence within relevant hosts. PMID:25690096

  17. Suppression of fibroblast proliferation by oral spirochetes.

    PubMed Central

    Boehringer, H; Taichman, N S; Shenker, B J

    1984-01-01

    Soluble sonic extracts of several strains of Treponema denticola and Treponema vincentii were examined for their abilities to alter proliferation of both murine and human fibroblasts. We found that sonic extracts of all tested strains of T. denticola caused a dose-dependent inhibition of murine and human fibroblast proliferation when assessed by both DNA synthesis ([3H]thymidine incorporation) and direct cell counts. T. vincentii had only a minimal inhibitory effect at comparable doses. No inhibition was observed when sonic extracts were added simultaneously with [3H]thymidine, indicating that suppression was not due to the presence of excessive amounts of cold thymidine in the extract, nonspecific effects on thymidine utilization by the cells (transport and incorporation), or degradation of label. RNA ([3H]uridine incorporation) and protein ([3H]leucine incorporation) synthesis were similarly altered after exposure to the T. denticola sonic extracts. There was no effect on cell viability as measured by trypan blue exclusion. Inhibition could be reversed by extensive washing of the cells within the first few hours of exposure to sonic extracts. Preliminary characterization and purification indicated that the inhibitory factor(s) is not endotoxin since it is heat labile, and elutes in a single, well-defined peak on a Sephadex G-150 chromatography column corresponding to a molecular weight of approximately 50,000. Since oral spirochetes have been implicated in the pathogenesis of periodontal disorders, it is possible that they contribute to the disease process by inhibition of fibroblast growth and therefore may, at least in part, account for the loss of collagen seen in diseased tissue. PMID:6735466

  18. Minimal role of eastern fence lizards in Borrelia burgdorferi transmission in central New Jersey oak/pine woodlands

    USGS Publications Warehouse

    Rulison, Eric L.; Kerr, Kaetlyn T; Dyer, Megan C; Han, Seungeun; Burke, Russell L.; Tsao, Jean I.; Ginsberg, Howard S.

    2014-01-01

    The Eastern fence lizard, Sceloporus undulatus, is widely distributed in eastern and central North America, ranging through areas with high levels of Lyme disease, as well as areas where Lyme disease is rare or absent. We studied the potential role of S. undulatus in transmission dynamics of Lyme spirochetes by sampling ticks from a variety of natural hosts at field sites in central New Jersey, and by testing the reservoir competence of S. undulatus for Borrelia burgdorferi in the laboratory. The infestation rate of ticks on fence lizards was extremely low (proportion infested = 0.087, n = 23) compared to that on white footed mice and other small mammals (proportion infested = 0.53, n = 140). Of 159 nymphs that had fed as larvae on lizards that had previously been exposed to infected nymphs, none was infected with B. burgdorferi, compared with 79.9% of 209 nymphs that had fed as larvae on infected control mice. Simulations suggest that changes in the numbers of fence lizards in a natural habitat would have little effect on the infection rate of nymphal ticks with Lyme spirochetes. We conclude that in central New Jersey S. undulatus plays a minimal role in the enzootic transmission cycle of Lyme spirochetes.

  19. Infestation of the southern alligator lizard (Squamata: Anguidae) by Ixodes pacificus (Acari: Ixodidae) and its susceptibility to Borrelia burgdorferi.

    PubMed

    Wright, S A; Lane, R S; Clover, J R

    1998-11-01

    To investigate the reservoir potential of the southern alligator lizard, Elgaria multicarinata (Blainville), for the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, 14 lizards were collected from 1 county on each side of the northern Central Valley of California. Seven animals were collected from a Placer County site (Drivers Flat) and a Yolo County site (Cache Creek) where B. burgdorferi had been isolated previously from Ixodes pacificus Cooley & Kohls. Overall, the mean abundance of I. pacificus on all 14 lizards was 34.1 (range, 3-63) for larvae and 11.0 (range, 1-28) for nymphs. In captivity, field-attached I. pacificus larvae and nymphs required, on average, 12.6 (range, 1-37) and 14.4 (range, 5-44) d to feed to repletion, respectively. The prevalence of B. burgdorferi infection in host-seeking I. pacificus nymphs was 1.4% in Cache Creek Canyon and 9.9% in Drivers Flat. Attempts to isolate spirochetes from lizard blood or ticks that had fed on lizards and subsequently molted were unsuccessful as were efforts to cultivate spirochetes in lizard sera. These data suggest that the southern alligator lizard is not a competent reservoir for B. burgdorferi, although it is an important host for I. pacificus subadults. PMID:9835700

  20. Cryoelectron tomography reveals the sequential assembly of bacterial flagella in Borrelia burgdorferi.

    PubMed

    Zhao, Xiaowei; Zhang, Kai; Boquoi, Tristan; Hu, Bo; Motaleb, M A; Miller, Kelly A; James, Milinda E; Charon, Nyles W; Manson, Michael D; Norris, Steven J; Li, Chunhao; Liu, Jun

    2013-08-27

    Periplasmic flagella are essential for the distinctive morphology, motility, and infectious life cycle of the Lyme disease spirochete Borrelia burgdorferi. In this study, we genetically trapped intermediates in flagellar assembly and determined the 3D structures of the intermediates to 4-nm resolution by cryoelectron tomography. We provide structural evidence that secretion of rod substrates triggers remodeling of the central channel in the flagellar secretion apparatus from a closed to an open conformation. This open channel then serves as both a gateway and a template for flagellar rod assembly. The individual proteins assemble sequentially to form a modular rod. The hook cap initiates hook assembly on completion of the rod, and the filament cap facilitates filament assembly after formation of the mature hook. Cryoelectron tomography and mutational analysis thus combine synergistically to provide a unique structural blueprint of the assembly process of this intricate molecular machine in intact cells. PMID:23940315

  1. The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel

    PubMed Central

    Dyer, Adam; Brown, Gemma; Stejskal, Lenka; Laity, Peter R.; Bingham, Richard J.

    2015-01-01

    The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane, is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The outer membrane protein A (OmpA) domain is an eight-stranded membrane-spanning β-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work, we describe the identification of four novel OmpA-like β-barrels from Borrelia afzelii, the most common cause of erythema migrans (EM) rash in Europe. Structural characterization of one these proteins (BAPKO_0422) by SAXS and CD indicate a compact globular structure rich in β-strand consistent with a monomeric β-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO_0422 adopts a peanut shape with dimensions 25×45 Å (1 Å=0.1 nm). Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal phenylalanine residue commonly found in Proteobacterial OM proteins is replaced by isoleucine/leucine or asparagine. BAPKO_0422 is demonstrated to bind human factor H (fH) and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value. PMID:26181365

  2. Borrelia crocidurae infection of Ornithodoros erraticus (Lucas, 1849) ticks in Tunisia.

    PubMed

    Bouattour, Ali; Garnier, Martine; M'Ghirbi, Youmna; Sarih, M'hammed; Gern, Lise; Ferquel, Elisabeth; Postic, Danièle; Cornet, Muriel

    2010-11-01

    Tick-borne relapsing fever (TBRF) is caused by Borrelia species transmitted to humans by infected Ornithodoros sp. ticks. The disease has been rarely described in North Africa, and in Tunisia the local transmission of TBRF seems to have disappeared or is undiagnosed. A longitudinal study was conducted in 14 sites located in four different bioclimatic zones of Tunisia to assess both the distribution of Ornithodoros sp. and their infection rate with the relapsing fever Borrelia sp. Three polymerase chain reaction methods targeting the 16S rRNA, the intergenic spacer, and the fla (flagellin) genes were used and phylogenetic analyses were carried out. Three hundred and fifty-eight specimens of Ornithodoros were collected: O. erraticus (previously termed "small variety") (n = 190) and O. normandi (n = 168). Borrelia crocidurae DNA was detected in 15.1% of O. erraticus (small variety) (24 out of the 159 randomly selected for testing) collected in rodent burrows situated in the arid and Saharan areas in southern Tunisia. Molecular analysis targeting the 16S rRNA gene and the noncoding intergenic spacer domain showed good resolution for this Borrelia sp., although no molecular polymorphism was evidenced according to location. In contrast, none of the 133 O. normandi, also randomly selected for testing, was infected by Borrelia sp. and these ticks were restricted to the subhumid and semiarid zones in northern Tunisia. Both O. erraticus (small variety) and O. normandi were found in Tunisia and the high B. crocidurae infection rate found in O. erraticus highlights the risk of TBRF transmission in the southern part of the country.

  3. Borrelia infection in small mammals in West Africa and its relationship with tick occurrence inside burrows.

    PubMed

    Diatta, Georges; Duplantier, Jean-Marc; Granjon, Laurent; Bâ, Khalilou; Chauvancy, Gilles; Ndiaye, Mady; Trape, Jean-François

    2015-12-01

    Tick-borne relapsing fever (TBRF) is a zoonotic disease caused by several Borrelia species transmitted to humans by Ornithodoros tick vectors. In West Africa, Borrelia crocidurae is a common cause of disease in many rural populations. Small mammals act as reservoirs of infection. We report here the results of surveys that investigated the occurrence of B. crocidurae infection in rodents and insectivores from eight countries of West and Central Africa. Animals were identified at the species level and tested for Borrelia either by examination of thick blood film, intra-peritoneal inoculation of blood or brain tissues into laboratory mice, or by molecular techniques. A total of 4358 small mammals belonging to 38 species and 7 families were collected, including 3225 specimens collected in areas where the occurrence of Ornithodoros sonrai tick in rodent burrows was documented, and 1133 in areas where this tick was absent. In areas with O. sonrai, Borrelia infection was demonstrated in 287 of 3109 (9.2%) small mammals tested, and none was documented in 1004 animals tested from other areas. There was no relationship between the occurrence of Rhipicephalus, Hyaloma and Argas ticks in burrows and the distribution of Borrelia infection in small mammals. The 287 specimens infected by Borrelia belonged to 15 rodent and shrew species, including three Saharo-Sahelian species - Gerbillus gerbillus, Gerbillus occiduus and Gerbillus tarabuli - identified as reservoirs for TBRF with a distribution restricted to this area. In Sudan and Sudano-Sahelian areas, Arvicanthis niloticus, Mastomys erythroleucus and Mastomys huberti were the main reservoir of infection. Although most small mammals species collected had a large distribution in West and Central Africa, the fact that only animals collected in areas with O. sonrai were found infected suggest that this tick is the only vector of TBRF in rodents and insectivores in this part of Africa. PMID:26327444

  4. The Nucleotide Excision Repair Pathway Protects Borrelia burgdorferi from Nitrosative Stress in Ixodes scapularis Ticks.

    PubMed

    Bourret, Travis J; Lawrence, Kevin A; Shaw, Jeff A; Lin, Tao; Norris, Steven J; Gherardini, Frank C

    2016-01-01

    The Lyme disease spirochete Borrelia burgdorferi encounters a wide range of environmental conditions as it cycles between ticks of the genus Ixodes and its various mammalian hosts. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are potent antimicrobial molecules generated during the innate immune response to infection, however, it is unclear whether ROS and RNS pose a significant challenge to B. burgdorferi in vivo. In this study, we screened a library of B. burgdorferi strains with mutations in DNA repair genes for increased susceptibility to ROS or RNS in vitro. Strains with mutations in the methyl-directed mismatch repair gene mutS1 are hypersensitive to killing by ROS, while strains lacking the nucleotide excision repair (NER) gene uvrB show increased susceptibility to both ROS and RNS. Therefore, mutS1-deficient and uvrB-deficient strains were compared for their ability to complete their infectious cycle in Swiss Webster mice and I. scapularis ticks to help identify sites of oxidative and nitrosative stresses encountered by B. burgdorferi in vivo. Both mutS1 and uvrB were dispensable for infection of mice, while uvrB promoted the survival of spirochetes in I. scapularis ticks. The decreased survival of uvrB-deficient B. burgdorferi was associated with the generation of RNS in I. scapularis midguts and salivary glands during feeding. Collectively, these data suggest that B. burgdorferi must withstand cytotoxic levels of RNS produced during infection of I. scapularis ticks. PMID:27656169

  5. Increasing density and Borrelia burgdorferi infection of deer-infesting Ixodes dammini (Acari: Ixodidae) in Maryland.

    PubMed

    Amerasinghe, F P; Breisch, N L; Neidhardt, K; Pagac, B; Scott, T W

    1993-09-01

    A statewide survey of Ixodes dammini Spielman was done in November 1991 as a follow-up to a study in 1989. In total, 3,434 adult ticks were collected from 922 hunter-killed white-tailed deer processed at 22 check stations (1 per county in 22 of 23 counties in the state). Significantly more male than female ticks were collected. Tick infestation was significantly heavier on male than female deer. The pattern of tick distribution was similar to that in 1989, with low prevalence (percentage tick-infested deer) and abundance (mean ticks per deer) in the Appalachian region, moderate values in the Piedmont, and high values in the western and eastern Coastal Plains regions. The pattern of tick infection with Borrelia burgdorferi spirochetes (determined by polyclonal immunofluorescence assay) was similar to the tick distributional pattern. Overall, tick prevalence and abundance were higher in 1991 than in 1989, as was the spirochete infection rate in ticks. Multiple regression analysis of tick prevalence against six selected physical and biotic parameters (elevation, rainfall, summer and winter temperature, percentage of forest land, deer density) showed a significant relationship with rainfall and elevation in 1989 and elevation alone in 1991. A more extensive study in Caroline and Dorchester counties in the eastern Coastal Plains region (which showed exceptionally low tick density indices in a generally tick-abundant region in 1989) demonstrated that I. dammini was well established in Caroline but not in Dorchester County. PMID:8254631

  6. Inability of Ixodes cookei and Amblyomma americanum nymphs (Acari: Ixodidae) to transmit Borrelia burgdorferi.

    PubMed

    Ryder, J W; Pinger, R R; Glancy, T

    1992-05-01

    The vector competency of Ixodes cookei Packard and Amblyomma americanum (L.) for Borrelia burgdorferi was studied using Syrian hamsters. Ixodes dammini Spielman, Clifford, Piesman & Corwin were used as controls. Darkfield and immunofluorescent examinations of midgut diverticula revealed B. burgdorferi spirochetes in 32 of 36 (88.9%) I. dammini larvae, 5 of 36 (13.9%) I. cookei larvae, and 7 of 36 (19.4%) A. americanum larvae within 48 h after feeding on infected Syrian hamsters. B. burgdorferi were also observed in the midguts of 94 of 107 (87.8%) I. dammini nymphs that developed from the fed larvae. However, none of 30 I. cookei nymphs was positive for spirochetes and only 1 of 60 (1.7%) A. americanum nymphs was found positive for B. burgdorferi. Nymphs of each tick species, reared from larvae that had fed on infected hamsters, were allowed to feed on uninfected hamsters to determine their ability to transmit B. burgdorferi. Transmission was demonstrated only by I. dammini nymphs.

  7. In vitro susceptibilities of Leptospira spp. and Borrelia burgdorferi isolates to amoxicillin, tilmicosin, and enrofloxacin.

    PubMed

    Kim, Doo; Kordick, Dorsey; Divers, Thomas; Chang, Yung Fu

    2006-12-01

    Antimicrobial susceptibility testing was conducted with 6 different spirochetal strains (4 strains of Leptospira spp. and 2 strains of Borrelia burgdorferi) against 3 antimicrobial agents, commonly used in equine and bovine practice. The ranges of MIC and MBC of amoxicillin against Leptospira spp. were 0.05 - 6.25 microgram/ml and 6.25 - 25.0 microgram/ml, respectively. And the ranges of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of amoxicillin against B. burgdorferi were 0.05 - 0.39 microgram/ml and 0.20 - 0.78 microgram/ml, respectively. The ranges of MIC and MBC of enrofloxacin against Leptospira spp. were 0.05 - 0.39 microgram/ml and 0.05 - 0.39 microgram/ml, respectively. Two strains of B. burgdorferi were resistant to enrofloxacin at the highest concentration tested for MBC (>or=100 microgram/ml). Therefore, the potential role of tilmicosin in the treatment of leptospirosis and borreliosis should be further evaluated in animal models to understand whether the in vivo studies will confirm in vitro results. All spirochetal isolates were inhibited (MIC) and were killed (MBC) by tilmicosin at concentrations below the limit of testing (

  8. In vitro susceptibilities of Leptospira spp. and Borrelia burgdorferi isolates to amoxicillin, tilmicosin, and enrofloxacin

    PubMed Central

    Kim, Doo; Kordick, Dorsey; Divers, Thomas

    2006-01-01

    Antimicrobial susceptibility testing was conducted with 6 different spirochetal strains (4 strains of Leptospira spp. and 2 strains of Borrelia burgdorferi) against 3 antimicrobial agents, commonly used in equine and bovine practice. The ranges of MIC and MBC of amoxicillin against Leptospira spp. were 0.05-6.25 µg/ml and 6.25-25.0 µg/ml, respectively. And the ranges of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of amoxicillin against B. burgdorferi were 0.05-0.39 µg/ml and 0.20-0.78 µg/ml, respectively. The ranges of MIC and MBC of enrofloxacin against Leptospira spp. were 0.05-0.39 µg/ml and 0.05-0.39 µg/ml, respectively. Two strains of B. burgdorferi were resistant to enrofloxacin at the highest concentration tested for MBC (≥100 µg/ml). Therefore, the potential role of tilmicosin in the treatment of leptospirosis and borreliosis should be further evaluated in animal models to understand whether the in vivo studies will confirm in vitro results. All spirochetal isolates were inhibited (MIC) and were killed (MBC) by tilmicosin at concentrations below the limit of testing (≤0.01 µg/ml). PMID:17106227

  9. The Nucleotide Excision Repair Pathway Protects Borrelia burgdorferi from Nitrosative Stress in Ixodes scapularis Ticks

    PubMed Central

    Bourret, Travis J.; Lawrence, Kevin A.; Shaw, Jeff A.; Lin, Tao; Norris, Steven J.; Gherardini, Frank C.

    2016-01-01

    The Lyme disease spirochete Borrelia burgdorferi encounters a wide range of environmental conditions as it cycles between ticks of the genus Ixodes and its various mammalian hosts. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are potent antimicrobial molecules generated during the innate immune response to infection, however, it is unclear whether ROS and RNS pose a significant challenge to B. burgdorferi in vivo. In this study, we screened a library of B. burgdorferi strains with mutations in DNA repair genes for increased susceptibility to ROS or RNS in vitro. Strains with mutations in the methyl-directed mismatch repair gene mutS1 are hypersensitive to killing by ROS, while strains lacking the nucleotide excision repair (NER) gene uvrB show increased susceptibility to both ROS and RNS. Therefore, mutS1-deficient and uvrB-deficient strains were compared for their ability to complete their infectious cycle in Swiss Webster mice and I. scapularis ticks to help identify sites of oxidative and nitrosative stresses encountered by B. burgdorferi in vivo. Both mutS1 and uvrB were dispensable for infection of mice, while uvrB promoted the survival of spirochetes in I. scapularis ticks. The decreased survival of uvrB-deficient B. burgdorferi was associated with the generation of RNS in I. scapularis midguts and salivary glands during feeding. Collectively, these data suggest that B. burgdorferi must withstand cytotoxic levels of RNS produced during infection of I. scapularis ticks.

  10. The Nucleotide Excision Repair Pathway Protects Borrelia burgdorferi from Nitrosative Stress in Ixodes scapularis Ticks

    PubMed Central

    Bourret, Travis J.; Lawrence, Kevin A.; Shaw, Jeff A.; Lin, Tao; Norris, Steven J.; Gherardini, Frank C.

    2016-01-01

    The Lyme disease spirochete Borrelia burgdorferi encounters a wide range of environmental conditions as it cycles between ticks of the genus Ixodes and its various mammalian hosts. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are potent antimicrobial molecules generated during the innate immune response to infection, however, it is unclear whether ROS and RNS pose a significant challenge to B. burgdorferi in vivo. In this study, we screened a library of B. burgdorferi strains with mutations in DNA repair genes for increased susceptibility to ROS or RNS in vitro. Strains with mutations in the methyl-directed mismatch repair gene mutS1 are hypersensitive to killing by ROS, while strains lacking the nucleotide excision repair (NER) gene uvrB show increased susceptibility to both ROS and RNS. Therefore, mutS1-deficient and uvrB-deficient strains were compared for their ability to complete their infectious cycle in Swiss Webster mice and I. scapularis ticks to help identify sites of oxidative and nitrosative stresses encountered by B. burgdorferi in vivo. Both mutS1 and uvrB were dispensable for infection of mice, while uvrB promoted the survival of spirochetes in I. scapularis ticks. The decreased survival of uvrB-deficient B. burgdorferi was associated with the generation of RNS in I. scapularis midguts and salivary glands during feeding. Collectively, these data suggest that B. burgdorferi must withstand cytotoxic levels of RNS produced during infection of I. scapularis ticks. PMID:27656169

  11. Borrelia burgdorferi: Carbon Metabolism and the Tick-Mammal Enzootic Cycle.

    PubMed

    Corona, Arianna; Schwartz, Ira

    2015-06-01

    Borrelia burgdorferi, the spirochetal agent of Lyme disease, is a zoonotic pathogen that is maintained in a natural cycle that typically involves mammalian reservoir hosts and a tick vector of the Ixodes species. During each stage of the enzootic cycle, B. burgdorferi is exposed to environments that differ in temperature, pH, small molecules, and most important, nutrient sources. B. burgdorferi has a highly restricted metabolic capacity because it does not contain a tricarboxylic acid cycle, oxidative phosphorylation, or any pathways for de novo biosynthesis of carbohydrates, amino acids, or lipids. Thus, B. burgdorferi relies solely on glycolysis for ATP production and is completely dependent on the transport of nutrients and cofactors from extracellular sources. Herein, pathways for carbohydrate uptake and utilization in B. burgdorferi are described. Regulation of these pathways during the different phases of the enzootic cycle is discussed. In addition, a model for differential control of nutrient flux through the glycolytic pathway as the spirochete transits through the enzootic cycle is presented.

  12. In vitro susceptibilities of Leptospira spp. and Borrelia burgdorferi isolates to amoxicillin, tilmicosin, and enrofloxacin.

    PubMed

    Kim, Doo; Kordick, Dorsey; Divers, Thomas; Chang, Yung Fu

    2006-12-01

    Antimicrobial susceptibility testing was conducted with 6 different spirochetal strains (4 strains of Leptospira spp. and 2 strains of Borrelia burgdorferi) against 3 antimicrobial agents, commonly used in equine and bovine practice. The ranges of MIC and MBC of amoxicillin against Leptospira spp. were 0.05 - 6.25 microgram/ml and 6.25 - 25.0 microgram/ml, respectively. And the ranges of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of amoxicillin against B. burgdorferi were 0.05 - 0.39 microgram/ml and 0.20 - 0.78 microgram/ml, respectively. The ranges of MIC and MBC of enrofloxacin against Leptospira spp. were 0.05 - 0.39 microgram/ml and 0.05 - 0.39 microgram/ml, respectively. Two strains of B. burgdorferi were resistant to enrofloxacin at the highest concentration tested for MBC (>or=100 microgram/ml). Therefore, the potential role of tilmicosin in the treatment of leptospirosis and borreliosis should be further evaluated in animal models to understand whether the in vivo studies will confirm in vitro results. All spirochetal isolates were inhibited (MIC) and were killed (MBC) by tilmicosin at concentrations below the limit of testing (

  13. BB0238, a presumed tetratricopeptide repeat-containing protein, is required during Borrelia burgdorferi mammalian infection.

    PubMed

    Groshong, Ashley M; Fortune, Danielle E; Moore, Brendan P; Spencer, Horace J; Skinner, Robert A; Bellamy, William T; Blevins, Jon S

    2014-10-01

    The Lyme disease spirochete, Borrelia burgdorferi, occupies both a tick vector and mammalian host in nature. Considering the unique enzootic life cycle of B. burgdorferi, it is not surprising that a large proportion of its genome is composed of hypothetical proteins not found in other bacterial pathogens. bb0238 encodes a conserved hypothetical protein of unknown function that is predicted to contain a tetratricopeptide repeat (TPR) domain, a structural motif responsible for mediating protein-protein interactions. To evaluate the role of bb0238 during mammalian infection, a bb0238-deficient mutant was constructed. The bb0238 mutant was attenuated in mice infected via needle inoculation, and complementation of bb0238 expression restored infectivity to wild-type levels. bb0238 expression does not change in response to varying culture conditions, and thus, it appears to be constitutively expressed under in vitro conditions. bb0238 is expressed in murine tissues during infection, though there was no significant change in expression levels among different tissue types. Localization studies indicate that BB0238 is associated with the inner membrane of the spirochete and is therefore unlikely to promote interaction with host ligands during infection. B. burgdorferi clones containing point mutations in conserved residues of the putative TPR motif of BB0238 demonstrated attenuation in mice that was comparable to that in the bb0238 deletion mutant, suggesting that BB0238 may contain a functional TPR domain.

  14. Rheumatic fever

    MedlinePlus

    ... an ASO test) Complete blood count (CBC) Electrocardiogram (EKG) Sedimentation rate (ESR -- a test that measures inflammation ... criteria include: Fever High ESR Joint pain Abnormal EKG You'll likely be diagnosed with rheumatic fever ...

  15. Dengue Fever

    MedlinePlus

    ... away from areas that have a dengue fever epidemic, the risk of contracting dengue fever is small for international travelers./p> Reviewed by: Elana Pearl Ben-Joseph, ... Nile Virus First Aid: Vomiting Are Insect Repellents With DEET ...

  16. Dengue Fever

    MedlinePlus

    ... Search Button Leading research to understand, treat, and prevent infectious, immunologic, and allergic diseases NIAID Home Health & ... NIAID News & Events Volunteer NIAID > Health & Research Topics > Dengue Fever > Understanding Dengue Fever Understanding Cause Transmission Symptoms ...

  17. Yellow fever

    MedlinePlus

    ... against yellow fever. Some countries require proof of vaccination to gain entry. If you will be traveling to an area where yellow fever is common: Sleep in screened housing Use mosquito repellents Wear ...

  18. Hemorrhagic Fevers

    MedlinePlus

    ... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

  19. Resurgence of Persisting Non-Cultivable Borrelia burgdorferi following Antibiotic Treatment in Mice

    PubMed Central

    Hodzic, Emir; Imai, Denise; Feng, Sunlian; Barthold, Stephen W.

    2014-01-01

    The agent of Lyme borreliosis, Borrelia burgdorferi, evades host immunity and establishes persistent infections in its varied mammalian hosts. This persistent biology may pose challenges to effective antibiotic treatment. Experimental studies in dogs, mice, and non-human primates have found persistence of B. burgdorferi DNA following treatment with a variety of antibiotics, but persisting spirochetes are non-cultivable. Persistence of B. burgdorferi DNA has been documented in humans following treatment, but the significance remains unknown. The present study utilized a ceftriaxone treatment regimen in the C3H mouse model that resulted in persistence of non-cultivable B. burgdorferi in order to determine their long-term fate, and to examine their effects on the host. Results confirmed previous studies, in which B. burgdorferi could not be cultured from tissues, but low copy numbers of B. burgdorferi flaB DNA were detectable in tissues at 2, 4 and 8 months after completion of treatment, and the rate of PCR-positive tissues appeared to progressively decline over time. However, there was resurgence of spirochete flaB DNA in multiple tissues at 12 months, with flaB DNA copy levels nearly equivalent to those found in saline-treated mice. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, flaB DNA was acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues by immunofluorescence and immunohistochemistry, respectively. A number of host cytokines were up- or down-regulated in tissues of both saline- and antibiotic-treated mice in the absence of histopathology, indicating host response to the presence of non-cultivable, despite the lack of inflammation in tissues. PMID:24466286

  20. Use of an endogenous plasmid locus for stable in trans complementation in Borrelia burgdorferi.

    PubMed

    Kasumba, Irene N; Bestor, Aaron; Tilly, Kit; Rosa, Patricia A

    2015-02-01

    Targeted mutagenesis and complementation are important tools for studying genes of unknown function in the Lyme disease spirochete Borrelia burgdorferi. A standard method of complementation is reintroduction of a wild-type copy of the targeted gene on a shuttle vector. However, shuttle vectors are present at higher copy numbers than B. burgdorferi plasmids and are potentially unstable in the absence of selection, thereby complicating analyses in the mouse-tick infectious cycle. B. burgdorferi has over 20 plasmids, with some, such as linear plasmid 25 (lp25), carrying genes required by the spirochete in vivo but relatively unstable during in vitro cultivation. We propose that complementation on an endogenous plasmid such as lp25 would overcome the copy number and in vivo stability issues of shuttle vectors. In addition, insertion of a selectable marker on lp25 could ensure its stable maintenance by spirochetes in culture. Here, we describe the construction of a multipurpose allelic-exchange vector containing a multiple-cloning site and either of two selectable markers. This suicide vector directs insertion of the complementing gene into the bbe02 locus, a site on lp25 that was previously shown to be nonessential during both in vitro and in vivo growth. We demonstrate the functional utility of this strategy by restoring infectivity to an ospC mutant through complementation at this site on lp25 and stable maintenance of the ospC gene throughout mouse infection. We conclude that this represents a convenient and widely applicable method for stable gene complementation in B. burgdorferi.

  1. Isolation and characterization of Borrelia burgdorferi from blood of a bird captured in the Saint Croix River Valley.

    PubMed Central

    McLean, R G; Ubico, S R; Hughes, C A; Engstrom, S M; Johnson, R C

    1993-01-01

    Field investigations were conducted to further evaluate the role of birds in the maintenance and dissemination of Borrelia burgdorferi. Blood specimens were taken from 39 passerine birds of 17 species captured during June 1991 at the Saint Croix National Riverway in Wisconsin, and one isolate, WI91-23, was cultured from an adult song sparrow (Melospiza melodia). This isolate was shown to be infectious for Peromyscus leucopus and Mesocricetus auratus (golden hamster). Isolate WI91-23 was confirmed as B. burgdorferi by immunofluorescence assay by using species-specific anti-OspA monoclonal antibodies H3TS and H5332 and anti-OspB antibody H5TS. Isolate WI91-23 was compared with Borrelia anserina Es, Borrelia hermsii MAN-1, and other B. burgdorferi strains (ATCC 53210, CT-1, and Catharus fuscescens [veery] liver 10293). Pulsed-field gel electrophoresis of in situ-lysed spirochetes revealed that the DNA plasmid profile of WI91-23 was most similar to those of plasmids from B. burgdorferi and most different from those of plasmids from B. anserina and B. hermsii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that the protein profile of WI91-23 was like that of other B. burgdorferi strains studied, with dominant proteins corresponding to OspA and OspB, and that it differed from the protein profiles of B. anserina and B. hermsii. These findings indicate that passerine birds may serve as reservoirs for B. burgdorferi. Images PMID:8370728

  2. Lyme disease in California: interrelationship of Ixodes pacificus (Acari: Ixodidae), the western fence lizard (Sceloporus occidentalis), and Borrelia burgdorferi.

    PubMed

    Lane, R S; Loye, J E

    1989-07-01

    The relationship of immature western black-legged ticks, Ixodes pacificus Cooley and Kohls, to the western fence lizard, Sceloporus occidentalis Baird and Girard, and to the Lyme disease spirochete, Borrelia burgdorferi, was investigated in chaparral and woodland-grass habitats in northern California from 1984 to 1986. Immature ticks were found on lizards in spring and summer, but the prevalence and abundance of ticks on this host were considerably greater in spring. The peak of larval abundance preceded that of nymphs by several weeks, but there was considerable seasonal overlap between these parasitic stages. Larvae and nymphs attached primarily to the lateral nuchal pockets of lizards in chaparral (99.5%) and woodland-grass (91.8%). The numbers of larvae infesting lizards in spring fit the negative binomial distribution in woodland-grass but not in chaparral; insufficient data precluded similar analyses for nymphs. Tick loads did not differ significantly with respect to age or gender of the lizard. Spirochetal infection rates (range, 0-3.7%) in I. pacificus immatures were comparable in both habitats and were similar to those reported previously for adults of this tick. Overall, 1 (0.9%) of 117 larvae and 10 (1.8%) of 552 nymphs were infected with spirochetes resembling B. burgdorferi. Spirochetes were not observed in blood smears prepared from 261 wild-caught lizards, including five lizards fed upon by infected ticks at the time of collection. These and other findings suggest that S. occidentalis, although an important host of I. pacificus immatures, may be less important as a source for infecting ticks with B. burgdorferi. PMID:2769705

  3. Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes

    PubMed Central

    Cervantes, Jorge L.; La Vake, Carson J.; Weinerman, Bennett; Luu, Stephanie; O'Connell, Caitlin; Verardi, Paulo H.; Salazar, Juan C.

    2013-01-01

    Phagocytosed Borrelia burgdorferi (Bb), the Lyme disease spirochete, induces a robust and complex innate immune response in human monocytes, in which TLR8 cooperates with TLR2 in the induction of NF-κB-mediated cytokine production, whereas TLR8 is solely responsible for transcription of IFN-β through IRF7. We now establish the role of Bb RNA in TLR8-mediated induction of IFN-β. First, using TLR2-transfected HEK.293 cells, which were unable to phagocytose intact Bb, we observed TLR2 activation by lipoprotein-rich borrelial lysates and TLR2 synthetic ligands but not in response to live spirochetes. Purified Bb RNA, but not borrelial DNA, triggered TLR8 activation. Neither of these 2 ligands induced activation of TLR7. Using purified human monocytes we then show that phagocytosed live Bb, as well as equivalent amounts of borrelial RNA delivered into the phagosome by polyethylenimine (PEI), induces transcription of IFN-β and secretion of TNF-α. The cytokine response to purified Bb RNA was markedly impaired in human monocytes naturally deficient in IRAK-4 and in cells with knockdown TLR8 expression by small interfering RNA. Using confocal microscopy we provide evidence that TLR8 colocalizes with internalized Bb RNA in both early (EEA1) and late endosomes (LAMP1). Live bacterial RNA staining indicates that spirochetal RNA does not transfer from the phagosome into the cytosol. Using fluorescent dextran particles we show that phagosomal integrity in Bb-infected monocytes is not affected. We demonstrate, for the first time, that Bb RNA is a TLR8 ligand in human monocytes and that transcription of IFN-β in response to the spirochete is induced from within the phagosomal vacuole through the TLR8-MyD88 pathway. PMID:23906644

  4. Correction: In Vivo Expression Technology Identifies a Novel Virulence Factor Critical for Borrelia burgdorferi Persistence in Mice.

    PubMed

    Ellis, Tisha Choudhury; Jain, Sunny; Linowski, Angelika K; Rike, Kelli; Bestor, Aaron; Rosa, Patricia A; Halpern, Micah; Kurhanewicz, Stephanie; Jewett, Mollie W

    2014-06-01

    Analysis of the transcriptome of Borrelia burgdorferi, the causative agent of Lyme disease, during infection has proven difficult due to the low spirochete loads in the mammalian tissues. To overcome this challenge, we have developed an In Vivo Expression Technology (IVET) system for identification of B. burgdorferi genes expressed during an active murine infection. Spirochetes lacking linear plasmid (lp) 25 are non-infectious yet highly transformable.Mouse infection can be restored to these spirochetes by expression of the essential lp25-encoded pnc A gene alone. Therefore, this IVET-based approach selects for in vivo-expressed promoters that drive expression of pncA resulting in the recovery of infectious spirochetes lacking lp25 following a three week infection in mice.Screening of approximately 15,000 clones in mice identified 289 unique in vivo-expressed DNA fragments from across all 22 replicons of the B. burgdorferi B31 genome. The in vivo-expressed candidate genes putatively encode proteins in various functional categories including antigenicity, metabolism, motility, nutrient transport and unknown functions. Candidate gene bbk46 on essential virulence plasmid lp36 was found to be highly induced in vivo and to be RpoS-independent. The bbk46 gene was dispensable for B. burgdorferi infection in mice. Our findings highlight the power of the IVET-based approach for identification of B. burgdorferi in vivo-expressed genes, which might not be discovered using other genome-wide gene expression methods. Further investigation of the novel in vivo-expressed candidate genes will contribute to advancing the understanding of molecular mechanisms of B.burgdorferi survival and pathogenicity in the mammalian host. PMID:24950221

  5. Lyme disease in California: interrelationship of Ixodes pacificus (Acari: Ixodidae), the western fence lizard (Sceloporus occidentalis), and Borrelia burgdorferi.

    PubMed

    Lane, R S; Loye, J E

    1989-07-01

    The relationship of immature western black-legged ticks, Ixodes pacificus Cooley and Kohls, to the western fence lizard, Sceloporus occidentalis Baird and Girard, and to the Lyme disease spirochete, Borrelia burgdorferi, was investigated in chaparral and woodland-grass habitats in northern California from 1984 to 1986. Immature ticks were found on lizards in spring and summer, but the prevalence and abundance of ticks on this host were considerably greater in spring. The peak of larval abundance preceded that of nymphs by several weeks, but there was considerable seasonal overlap between these parasitic stages. Larvae and nymphs attached primarily to the lateral nuchal pockets of lizards in chaparral (99.5%) and woodland-grass (91.8%). The numbers of larvae infesting lizards in spring fit the negative binomial distribution in woodland-grass but not in chaparral; insufficient data precluded similar analyses for nymphs. Tick loads did not differ significantly with respect to age or gender of the lizard. Spirochetal infection rates (range, 0-3.7%) in I. pacificus immatures were comparable in both habitats and were similar to those reported previously for adults of this tick. Overall, 1 (0.9%) of 117 larvae and 10 (1.8%) of 552 nymphs were infected with spirochetes resembling B. burgdorferi. Spirochetes were not observed in blood smears prepared from 261 wild-caught lizards, including five lizards fed upon by infected ticks at the time of collection. These and other findings suggest that S. occidentalis, although an important host of I. pacificus immatures, may be less important as a source for infecting ticks with B. burgdorferi.

  6. Geographic distribution of white-tailed deer with ticks and antibodies to Borrelia burgdorferi in Connecticut.

    PubMed

    Magnarelli, L A; Anderson, J F; Cartter, M L

    1993-01-01

    Ticks and blood specimens were collected from white-tailed deer (Odocoileus virginianus) in Connecticut and analyzed to identify foci for Lyme borreliosis. Males and females of Ixodes scapularis, the chief vector of Borrelia burgdorferi, were collected from deer in five of eight counties during 1989-1991. Analysis by indirect fluorescent antibody (IFA) staining of midgut tissues showed that prevalence of infection was highest (9.5% of 367 ticks) in south central and southeastern Connecticut. Infected I. scapularis also were collected from southwestern regions of the state (12.1% of 99 ticks), but prevalence of infection in northern counties was considerably lower (0.8% of 124 ticks). Deer sera, obtained in 1980 and 1989-1991, were analyzed by an enzyme-linked immunosorbent assay or by IFA staining methods. Antibodies to B. burgdorferi were detected in sera collected from all eight counties in Connecticut. Deer had been infected by this spirochete in at least 50 towns, 17 (34%) of which are in south central and southeastern parts of the state. Borrelia burgdorferi is widely distributed in I. scapularis populations in Connecticut. PMID:8256460

  7. CspA from Borrelia burgdorferi Inhibits the Terminal Complement Pathway

    PubMed Central

    Hallström, Teresia; Siegel, Corinna; Mörgelin, Matthias; Kraiczy, Peter; Skerka, Christine; Zipfel, Peter F.

    2013-01-01

    ABSTRACT In order to survive and persist in an immunocompetent human host, Borrelia burgdorferi controls the human immune attack and blocks the damaging effects of the activated complement system. These Gram-negative spirochetes use CspA (CRASP-1) and four additional immune evasion proteins to bind combinations of human plasma regulators, including factor H, factor H-like protein 1 (FHL-1), complement factor H-related protein 1 (CFHR1), CFHR2, CFHR5, and plasminogen. As many microbial immune evasion proteins have multiple functions, we hypothesized that CspA has additional roles in complement or immune control. Here, we identify CspA as a terminal complement inhibitor. Borrelial CspA binds the human terminal complement components C7 and C9 and blocks assembly and membrane insertion of the terminal complement complex (TCC). CspA inhibits TCC assembly at the level of C7, as revealed by hemolytic assays, and inhibits polymerization of C9. CspA, when ectopically expressed on the surface of serum-sensitive Borrelia garinii, blocks TCC assembly on the level of C7 and induces serum resistance in the transformed bacteria. This CspA-mediated serum resistance and terminal complement pathway inhibition allow B. burgdorferi to survive in the hostile environment of human plasma. PMID:23943762

  8. Interleukin-10 alters effector functions of multiple genes induced by Borrelia burgdorferi in macrophages to regulate Lyme disease inflammation.

    PubMed

    Gautam, Aarti; Dixit, Saurabh; Philipp, Mario T; Singh, Shree R; Morici, Lisa A; Kaushal, Deepak; Dennis, Vida A

    2011-12-01

    Interleukin-10 (IL-10) modulates inflammatory responses elicited in vitro and in vivo by Borrelia burgdorferi, the Lyme disease spirochete. How IL-10 modulates these inflammatory responses still remains elusive. We hypothesize that IL-10 inhibits effector functions of multiple genes induced by B. burgdorferi in macrophages to control concomitantly elicited inflammation. Because macrophages are essential in the initiation of inflammation, we used mouse J774 macrophages and live B. burgdorferi spirochetes as the model target cell and stimulant, respectively. First, we employed transcriptome profiling to identify genes that were induced by stimulation of cells with live spirochetes and that were perturbed by addition of IL-10 to spirochete cultures. Spirochetes significantly induced upregulation of 347 genes at both the 4-h and 24-h time points. IL-10 inhibited the expression levels, respectively, of 53 and 65 of the 4-h and 24-h genes, and potentiated, respectively, at 4 h and 24 h, 65 and 50 genes. Prominent among the novel identified IL-10-inhibited genes also validated by quantitative real-time PCR (qRT-PCR) were Toll-like receptor 1 (TLR1), TLR2, IRAK3, TRAF1, IRG1, PTGS2, MMP9, IFI44, IFIT1, and CD40. Proteome analysis using a multiplex enzyme-linked immunosorbent assay (ELISA) revealed the IL-10 modulation/and or potentiation of RANTES/CCL5, macrophage inflammatory protein 2 (MIP-2)/CXCL2, IP-10/CXCL10, MIP-1α/CCL3, granulocyte colony-stimulating factor (G-CSF)/CSF3, CXCL1, CXCL5, CCL2, CCL4, IL-6, tumor necrosis factor alpha (TNF-α), IL-1α, IL-1β, gamma interferon (IFN-γ), and IL-9. Similar results were obtained using sonicated spirochetes or lipoprotein as stimulants. Our data show that IL-10 alters effectors induced by B. burgdorferi in macrophages to control concomitantly elicited inflammatory responses. Moreover, for the first time, this study provides global insight into potential mechanisms used by IL-10 to control Lyme disease inflammation.

  9. Stage-Specific Global Alterations in the Transcriptomes of Lyme Disease Spirochetes During Tick Feeding and Following Mammalian Host-Adaptation

    PubMed Central

    Iyer, Radha; Caimano, Melissa J.; Luthra, Amit; Axline, David; Corona, Arianna; Iacobas, Dumitru A.; Radolf, Justin D.; Schwartz, Ira

    2015-01-01

    Borrelia burgdorferi, the agent of Lyme disease, is maintained in nature within an enzootic cycle involving a mammalian reservoir and an Ixodes sp. tick vector. The transmission, survival and pathogenic potential of B. burgdorferi depend on the bacterium’s ability to modulate its transcriptome as it transits between vector and reservoir host. Herein, we employed an amplification-microarray approach to define the B. burgdorferi transcriptomes in fed larvae, fed nymphs and in mammalian host-adapted organisms cultivated in dialysis membrane chambers. The results show clearly that spirochetes exhibit unique expression profiles during each tick stage and during cultivation within the mammal; importantly, none of these profiles resembles that exhibited by in vitro-grown organisms. Profound shifts in transcript levels were observed for genes encoding known or predicted lipoproteins as well as proteins involved in nutrient uptake, carbon utilization and lipid synthesis. Stage-specific expression patterns of chemotaxis-associated genes also were noted, suggesting that the composition and interactivities of the chemotaxis machinery components vary considerably in the feeding tick and mammal. The results as a whole make clear that environmental sensing by B. burgdorferi directly or indirectly drives an extensive and tightly integrated modulation of cell envelope constituents, chemotaxis/motility machinery, intermediary metabolism and cellular physiology. These findings provide the necessary transcriptional framework for delineating B. burgdorferi regulatory pathways throughout the enzootic cycle as well as defining the contribution(s) of individual genes to spirochete survival in nature and virulence in humans. PMID:25425211

  10. Global repression of host-associated genes of the Lyme disease spirochete through post-transcriptional modulation of the alternative sigma factor RpoS.

    PubMed

    Dulebohn, Daniel P; Hayes, Beth M; Rosa, Patricia A

    2014-01-01

    Borrelia burgdorferi, the agent of Lyme disease, is a vector-borne pathogen that transits between Ixodes ticks and vertebrate hosts. During the natural infectious cycle, spirochetes must globally adjust their transcriptome to survive in these dissimilar environments. One way B. burgdorferi accomplishes this is through the use of alternative sigma factors to direct transcription of specific genes. RpoS, one of only three sigma factors in B. burgdorferi, controls expression of genes required during tick-transmission and infection of the mammalian host. How spirochetes switch between different sigma factors during the infectious cycle has remained elusive. Here we establish a role for a novel protein, BBD18, in the regulation of the virulence-associated sigma factor RpoS. Constitutive expression of BBD18 repressed transcription of RpoS-dependent genes to levels equivalent to those observed in an rpoS mutant. Consistent with the global loss of RpoS-dependent transcripts, we were unable to detect RpoS protein. However, constitutive expression of BBD18 did not diminish the amount of rpoS transcript, indicating post-transcriptional regulation of RpoS by BBD18. Interestingly, BBD18-mediated repression of RpoS is independent of both the rpoS promoter and the 5' untranslated region, suggesting a mechanism of protein destabilization rather than translational control. We propose that BBD18 is a novel regulator of RpoS and its activity likely represents a first step in the transition from an RpoS-ON to an RpoS-OFF state, when spirochetes transition from the host to the tick vector.

  11. HrpA, an RNA helicase involved in RNA processing, is required for mouse infectivity and tick transmission of the Lyme disease spirochete.

    PubMed

    Salman-Dilgimen, Aydan; Hardy, Pierre-Olivier; Radolf, Justin D; Caimano, Melissa J; Chaconas, George

    2013-01-01

    The Lyme disease spirochete Borrelia burgdorferi must differentially express genes and proteins in order to survive in and transit between its tick vector and vertebrate reservoir. The putative DEAH-box RNA helicase, HrpA, has been recently identified as an addition to the spirochete's global regulatory machinery; using proteomic methods, we demonstrated that HrpA modulates the expression of at least 180 proteins. Although most bacteria encode an HrpA helicase, RNA helicase activity has never been demonstrated for HrpAs and the literature contains little information on the contribution of this protein to bacterial physiology or pathogenicity. In this work, we report that B. burgdorferi HrpA has RNA-stimulated ATPase activity and RNA helicase activity and that this enzyme is essential for both mammalian infectivity by syringe inoculation and tick transmission. Reduced infectivity of strains carrying mutations in the ATPase and RNA binding motif mutants suggests that full virulence expression requires both ATPase and coupled helicase activity. Microarray profiling revealed changes in RNA levels of two-fold, or less in an hrpA mutant versus wild-type, suggesting that the enzyme functions largely or exclusively at the post-transcriptional level. In this regard, northern blot analysis of selected gene products highly regulated by HrpA (bb0603 [p66], bba74, bb0241 [glpK], bb0242 and bb0243 [glpA]) suggests a role for HrpA in the processing and translation of transcripts. In addition to being the first demonstration of RNA helicase activity for a bacterial HrpA, our data indicate that the post-transcriptional regulatory functions of this enzyme are essential for maintenance of the Lyme disease spirochete's enzootic cycle.

  12. Niche partitioning of Borrelia burgdorferi and Borrelia miyamotoi in the same tick vector and mammalian reservoir species.

    PubMed

    Barbour, Alan G; Bunikis, Jonas; Travinsky, Bridgit; Hoen, Anne Gatewood; Diuk-Wasser, Maria A; Fish, Durland; Tsao, Jean I

    2009-12-01

    The Lyme borreliosis agent Borrelia burgdorferi and the relapsing fever group species Borrelia miyamotoi co-occur in the United States. We used species-specific, quantitative polymerase chain reaction to study both species in the blood and skin of Peromyscus leucopus mice and host-seeking Ixodes scapularis nymphs at a Connecticut site. Bacteremias with B. burgdorferi or B. miyamotoi were most prevalent during periods of greatest activity for nymphs or larvae, respectively. Whereas B. burgdorferi was 30-fold more frequent than B. miyamotoi in skin biopsies and mice had higher densities of B. burgdorferi densities in the skin than in the blood, B. miyamotoi densities were higher in blood than skin. In a survey of host-seeking nymphs in 11 northern states, infection prevalences for B. burgdorferi and B. miyamotoi averaged approximately 0.20 and approximately 0.02, respectively. Co-infections of P. leucopus or I. scapularis with both B. burgdorferi and B. miyamotoi were neither more nor less common than random expectations. PMID:19996447

  13. Novel methods for surveying reservoir hosts and vectors of Borrelia burgdorferi in Northern Minnesota

    NASA Astrophysics Data System (ADS)

    Seifert, Veronica Aili

    Lyme disease is the most prevalent tick-borne disease in North America and presents challenges to clinicians, researchers and the public in diagnosis, treatment and prevention. Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is a zoonotic pathogen obligate upon hematophagous arthropod vectors and propagates in small mammal reservoir hosts. Identifying factors governing zoonotic diseases within regions of high-risk provides local health and agricultural agencies with necessary information to formulate public policy and implement treatment protocols to abate the rise and expansion of infectious disease outbreaks. In the United States, the documented primary reservoir host of Lyme disease is the white-footed mouse, Peromyscus leucopus, and the arthropod vector is the deer tick, Ixodes scapularis. Reducing the impact of Lyme disease will need novel methods for identifying both the reservoir host and the tick vector. The reservoir host, Peromyscus leucopus is difficult to distinguish from the virtually identical Peromyscus maniculatus that also is present in Northern Minnesota, a region where Lyme disease is endemic. Collection of the Ixodes tick, the Lyme disease vector, is difficult as this is season dependent and differs from year to year. This study develops new strategies to assess the extent of Borrelia burgdorferi in the local environment of Northern Minnesota. A selective and precise method to identify Peromyscus species was developed. This assay provides a reliable and definitive method to identify the reservoir host, Peromyscus leucopus from a physically identical and sympatric Peromyscus species, Peromyscus maniculatus. A new strategy to collect ticks for measuring the disbursement of Borrelia was employed. Students from local high schools were recruited to collect ticks. This strategy increased the available manpower to cover greater terrain, provided students with valuable experience in research methodology, and highlighted the

  14. Borrelia burgdorferi Not Confirmed in Human-Biting Amblyomma americanum Ticks from the Southeastern United States

    PubMed Central

    Nadolny, Robyn M.; Gibbons, Jennifer A.; Auckland, Lisa D.; Vince, Mary A.; Elkins, Chad E.; Murphy, Michael P.; Hickling, Graham J.; Eshoo, Mark W.; Carolan, Heather E.; Crowder, Chris D.; Pilgard, Mark A.; Hamer, Sarah A.

    2015-01-01

    The predominant human-biting tick throughout the southeastern United States is Amblyomma americanum. Its ability to transmit pathogens causing Lyme disease-like illnesses is a subject of ongoing controversy. Results of previous testing by the Department of Defense Human Tick Test Kit Program and other laboratories indicated that it is highly unlikely that A. americanum transmits any pathogen that causes Lyme disease. In contrast, a recent publication by Clark and colleagues (K. L. Clark, B. Leydet, and S. Hartman, Int. J. Med. Sci. 10:915–931, 2013) reported detection of Lyme group Borrelia in A. americanum using a nested-flagellin-gene PCR. We evaluated this assay by using it and other assays to test 1,097 A. americanum ticks collected from humans. Using the Clark assay, in most samples we observed nonspecific amplification and nonrepeatability of results on subsequent testing of samples. Lack of reaction specificity and repeatability is consistent with mispriming, likely due to high primer concentrations and low annealing temperatures in this protocol. In six suspect-positive samples, Borrelia lonestari was identified by sequencing of an independent gene region; this is not a Lyme group spirochete and is not considered zoonotic. B. burgdorferi was weakly amplified from one pool using some assays, but not others, and attempts to sequence the amplicon of this pool failed, as did attempts to amplify and sequence B. burgdorferi from the five individual samples comprising this pool. Therefore, B. burgdorferi was not confirmed in any sample. Our results do not support the hypothesis that A. americanum ticks are a vector for Lyme group Borrelia infections. PMID:25788545

  15. Phylogenetic position and in situ identification of ectosymbiotic spirochetes on protists in the termite gut.

    PubMed

    Noda, Satoko; Ohkuma, Moriya; Yamada, Akinori; Hongoh, Yuichi; Kudo, Toshiaki

    2003-01-01

    Phylogenetic relationships, diversity, and in situ identification of spirochetes in the gut of the termite Neotermes koshunensis were examined without cultivation, with an emphasis on ectosymbionts attached to flagellated protists. Spirochetes in the gut microbial community investigated so far are related to the genus Treponema and divided into two phylogenetic clusters. In situ hybridizations with a 16S rRNA-targeting consensus oligonucleotide probe for one cluster (known as termite Treponema cluster I) detected both the ectosymbiotic spirochetes on gut protists and the free-swimming spirochetes in the gut fluid of N. koshunensis. The probe for the other cluster (cluster II), which has been identified as ectosymbionts on gut protists of two other termite species, Reticulitermes speratus and Hodotermopsis sjoestedti, failed to detect any spirochete population. The absence of cluster II spirochetes in N. koshunensis was confirmed by intensive 16S ribosomal DNA (rDNA) clone analysis, in which remarkably diverse spirochetes of 45 phylotypes were identified, almost all belonging to cluster I. Ectosymbiotic spirochetes of the three gut protist species Devescovina sp., Stephanonympha sp., and Oxymonas sp. in N. koshunensis were identified by their 16S rDNA and by in situ hybridizations using specific probes. The probes specific for these ectosymbionts did not receive a signal from the free-swimming spirochetes. The ectosymbionts were dispersed in cluster I of the phylogeny, and they formed distinct phylogenetic lineages, suggesting multiple origins of the spirochete attachment. Each single protist cell harbored multiple spirochete species, and some of the spirochetes were common among protist species. The results indicate complex relationships of the ectosymbiotic spirochetes with the gut protists.

  16. [Dengue fever].

    PubMed

    Pick, N; Potasman, I

    1995-07-01

    Dengue fever is a viral disease, transmitted to man via mosquito bites. It is endemic in tropical regions (10 million infected annually) and is characterized by high fever, headache, myalgia, lethargy, vomiting, rash and neutropenia. The upward trend in the number of young Israelis visiting tropical countries increases the number of those potentially exposed to this disease. We present 4 Israelis who returned with dengue fever from Thailand.

  17. Yellow fever.

    PubMed

    Monath, Thomas P; Vasconcelos, Pedro F C

    2015-03-01

    Yellow fever, a mosquito-borne flavivirus disease occurs in tropical areas of South America and Africa. It is a disease of major historical importance, but remains a threat to travelers to and residents of endemic areas despite the availability of an effective vaccine for nearly 70 years. An important aspect is the receptivity of many non-endemic areas to introduction and spread of yellow fever. This paper reviews the clinical aspects, pathogenesis, and epidemiology of yellow fever, with an emphasis on recent changes in the distribution and incidence of the disease. Recent knowledge about yellow fever 17D vaccine mechanism of action and safety are discussed.

  18. HLA-DR alleles determine responsiveness to Borrelia burgdoferi antigens

    PubMed Central

    Iliopoulou, Bettina Panagiota; Guerau-de-Arellano, Mireia; Huber, Brigitte T.

    2010-01-01

    Objective Arthritis is a prominent manifestation of Lyme disease, caused upon infection with Borrelia burgdorferi (Bb). Persistent chronic Lyme arthritis, even after antibiotic treatment, is linked to HLA-DRB1*0401 (DR4) and related alleles. On the contrary, Lyme patients who resolve arthritis within 3 months post-infection show an increased frequency of HLA-DRB1*1101 (DR11). The aim of this study was to analyze the underlying mechanism by which HLA-DR alleles confer genetic susceptibility or resistance to antibiotic-refractory Lyme arthritis. Methods We generated DR11 transgenic (tg) mice on a murine class II−/− background and compared their immune response to Bb-antigens to that of DR4 tg mice after immunization with Bb outer surface protein (Osp)A or infection with live Bb. Results We report that the T cells of OspA-immunized and Bb-infected DR11 tg mice were defective in IFN-γ production compared to those of DR4 mice. On the other hand, DR11 tg mice developed higher titers of anti-OspA and anti-Bb Abs, respectively, than DR4 mice. In accordance with this observation, we found that Bb-infected DR11 tg mice had decreased spirochetal burden compared to DR4 mice, measured by qPCR. Conclusion This study provides direct evidence that in the presence of HLA-DR11 the immune response against Bb-antigens is directed towards a protective Ab response. In contrast, an inflammatory Th1 response is induced in the presence of DR4. These observations offer an explanation for the differential genetic susceptibility of DR4+ and DR11+ individuals for the development of chronic Lyme arthritis and eventually the progression to antibiotic-refractory Lyme arthritis. PMID:19950279

  19. Host cell heparan sulfate glycosaminoglycans are ligands for OspF-related proteins of the Lyme disease spirochete.

    PubMed

    Lin, Yi-Pin; Bhowmick, Rudra; Coburn, Jenifer; Leong, John M

    2015-10-01

    Borrelia burgdorferi, the agent of Lyme disease, spreads from the site of the tick bite to tissues such as heart, joints and the nervous tissues. Host glycosaminoglycans, highly modified repeating disaccharides that are present on cell surfaces and in extracellular matrix, are common targets of microbial pathogens during tissue colonization. While several dermatan sulfate-binding B. burgdorferi adhesins have been identified, B. burgdorferi adhesins documented to promote spirochetal binding to heparan sulfate have not yet been identified. OspEF-related proteins (Erps), a large family of plasmid-encoded surface lipoproteins that are produced in the mammalian host, can be divided into the OspF-related, OspEF-leader peptide (Elp) and OspE-related subfamilies. We show here that a member of the OspF-related subfamily, ErpG, binds to heparan sulfate and when produced on the surface of an otherwise non-adherent B. burgdorferi strain, ErpG promotes heparan sulfate-mediated bacterial attachment to the glial but not the endothelial, synovial or respiratory epithelial cells. Six other OspF-related proteins were capable of binding heparan sulfate, whereas representative OspE-related and Elp proteins lacked this activity. These results indicate that OspF-related proteins are heparan sulfate-binding adhesins, at least one of which promotes bacterial attachment to glial cells.

  20. Host cell heparan sulfate glycosaminoglycans are ligands for OspF-related proteins of the Lyme disease spirochete

    PubMed Central

    Lin, Yi-Pin; Bhowmick, Rudra; Coburn, Jenifer; Leong, John M.

    2015-01-01

    Borrelia burgdorferi , the agent of Lyme disease, spreads from the site of the tick bite to tissues such as heart, joints and the nervous system. Host glycosaminoglycans (GAGs), highly modified repeating disaccharides that are present on cell surfaces and in extracellular matrix, are common targets of microbial pathogens during tissue colonization. While several dermatan sulfate-binding B. burgdorferi adhesins have been identified, B. burgdorferi adhesins documented to promote spirochetal binding to heparan sulfate have not yet been identified. OspEF-related proteins (Erps), a large family of plasmid-encoded surface lipoproteins that are produced in the mammalian host, can be divided into the OspF-related, OspEF leader peptide (Elp), and OspE-related subfamilies. We show here that a member of the OspF-related subfamily, ErpG, binds to heparan sulfate, and when produced on the surface of an otherwise nonadherent B. burgdorferi strain, ErpG promotes heparan sulfate-mediated bacterial attachment to glial but not endothelial, synovial or respiratory epithelial cells. Six other OspF-related proteins were capable of binding heparan sulfate, whereas representative OspE-related and Elp proteins lacked this activity. These results indicate that OspF-related proteins are heparan sulfate-binding adhesins, at least one of which promotes bacterial attachment to glial cells. PMID:25864455

  1. Lyme arthritis. Spirochetes found in synovial microangiopathic lesions.

    PubMed Central

    Johnston, Y. E.; Duray, P. H.; Steere, A. C.; Kashgarian, M.; Buza, J.; Malawista, S. E.; Askenase, P. W.

    1985-01-01

    In 17 patients with Lyme disease, synovial specimens, obtained by synovectomy or needle biopsy, showed nonspecific villous hypertrophy, synovial cell hyperplasia, prominent microvasculature, lymphoplasmacellular infiltration, and sometimes lymphoid follicles. The larger surgically obtained specimens also showed striking deposition of fibrin in synovial stroma and a form of endarteritis obliterans. In 2 patients, spirochetes were seen in and around blood vessels by the Dieterle silver stain. Compared with 55 cases of other synovial disease, obliterative microvascular lesions were seen only in Lyme synovia, but marked stromal deposition of fibrin seemed nonspecific. These findings imply that the Lyme spirochete may survive for years in affected synovium and may be directly responsible for the microvascular injury. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3966535

  2. Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease

    PubMed Central

    1996-01-01

    The outer surface proteins (Osps) of Borrelia burgdorferi, the etiologic agent of Lyme disease, are principle targets of protective immune responses against this organism. Whereas most North American strains of B. burgdorferi in culture express an abundant amount of Osp A, antibodies to this protein are either absent or only weakly detected in the sera of naturally infected patients or experimentally infected mice. In contrast, Osp C, which has variable expression on cultured organisms; elicits an early, strong humoral response. To examine this paradox, we have studied the in vivo adaptation of a cloned population of B. burgdorferi strain N40 during the early course of experimental murine borreliosis. As in human disease, antibodies to Osp A were only weakly present in the early immune repertoire after murine inoculation with low dose (10(3)) spirochetes. In contrast, antibodies to Osp C were prominent, even though on cultured spirochetes Osp C mRNA and protein expression could not be detected by reverse transcription polymerase chain reaction (RT-PCR) or indirect immunofluorescence, respectively. These observations led us to investigate the expression of Osp A and Osp C in vivo. By direct fluorescent staining of uncultured spirochetes ex vivo and by PCR amplification of spirochetal mRNA, we show that Osp C is indeed expressed by some spirochetes after infection in the mouse. Spirochetes expressing Osp A could also be detected within the first 2 wk of infection, but not at 30 d. Osp A mRNA, although present at day 14 of infection, could not be amplified by RT-PCR at day 30, suggesting that the expression of this Osp is transient. This further implies that the late burst in Osp A antibodies in both mice and humans may be anamnestic. These results indicate that either Osp C is upregulated on spirochetes after infection, or Osp C- expressing spirochetes expand preferentially over those expressing Osp A during infection. These results have important implications for

  3. Organized spirochetal behavior in human subgingival plaques - A virulence factor in periodontal infections?

    PubMed Central

    Keyes, Paul H.; Rams, Thomas E.

    2015-01-01

    The organization and behavior of spirochetes in human subgingival plaques was studied with phase-contrast microscopy. Wet-mounts of non-dispersed subgingival microbial specimens from deep pockets of 10 persons with untreated adult periodontitis revealed “brush formations” with outer coatings of closely-massed spirochetes exhibiting synchronized motility. Monolayers of closely-packed spirochetes co-aggregated with “brush formation” monofilaments were obtained by using mineral oil as a mounting medium for wet-mount preparations. Spirochetes were observed to produce collectively coordinated metachronal wave patterns with their cell movements along the outer surfaces of the “brush formation” monofilaments, rather than flexing independently and at random. Organized spirochetal activity in subgingival plaques may serve as a virulence factor contributing to the periodontopathic potential of spirochetes and/or other microbial species. PMID:26336331

  4. Cristispira from oyster styles: complex morphology of large symbiotic spirochetes

    NASA Technical Reports Server (NTRS)

    Margulis, L.; Nault, L.; Sieburth, J. M.

    1991-01-01

    Crystalline styles (digestive organs) of bivalve mollusks provide the habitat for highly motile bacteria. Styles from freshly-collected oysters, Crassostrea virginica, were studied by electron microscopy; Cristispira spirochetes were abundant in these organs. Detailed study reveals these spirochetes to be among the most complex prokaryotic cells known. More than 600 periplasmic flagella and an adhering outer lipoprotein membrane (e.g., a 270 degrees sillon) form the ultrastructural basis for the "crista," first described by light microscopy. Unique rosette structures corresponding to the "chambers" or "ovoid inclusions" of light microscopy were detected at the periphery of all protoplasmic cylinders. Polar organelles and linearly aligned flagellar insertions are conspicuous. In size and complexity, Cristispira more resembles Pillotina, Diplocalyx, Clevelandina and Hollandina (large spirochetes symbiotic in termites) than it does Treponema. Cristispira pectinis (Gross, 1910), the type species; Spirillum ostrea (Noguchi, 1921); and another, less frequent bacterial symbiont are the predominant inhabitants of the dense style matrix. The ultrastructure of the spirillum and an electron micrograph of the third bacterium are shown.

  5. Cardiac Apoptosis in Severe Relapsing Fever Borreliosis

    PubMed Central

    Londoño, Diana; Bai, Yunhong; Zückert, Wolfram R.; Gelderblom, Harald; Cadavid, Diego

    2005-01-01

    Previous studies revealed that the heart suffers significant injury during experimental Lyme and relapsing fever borreliosis when the immune response is impaired (D. Cadavid, Y. Bai, E. Hodzic, K. Narayan, S. W. Barthold, and A. R. Pachner, Lab. Investig. 84:1439-1450, 2004; D. Cadavid, T. O'Neill, H. Schaefer, and A. R. Pachner, Lab. Investig. 80:1043-1054, 2000; and D. Cadavid, D. D. Thomas, R. Crawley, and A. G. Barbour, J. Exp. Med. 179:631-642, 1994). To investigate cardiac injury in borrelia carditis, we used antibody-deficient mice persistently infected with isogenic serotypes of the relapsing fever agent Borrelia turicatae. We studied infection in hearts 1 to 2 months after inoculation by TaqMan reverse transcription-PCR and immunohistochemistry (IHC) and inflammation by hematoxylin and eosin and trichrome staining, IHC, and in situ hybridization (ISH). We studied apoptosis by terminal transferase-mediated DNA nick end labeling assay and measured expression of apoptotic molecules by RNase protection assay, immunofluorescence, and immunoblot. All antibody-deficient mice, but none of the immunocompetent controls, developed persistent infection of the heart. Antibody-deficient mice infected with serotype 2 had more severe cardiac infection and injury than serotype 1-infected mice. The injury was more severe around the base of the heart and pericardium, corresponding to sites of marked infiltration by activated macrophages and upregulation of interleukin-6 (IL-6). Infected hearts showed evidence of apoptosis of macrophages and cardiomyocytes as well as significant upregulation of caspases, most notably caspase-1. We conclude that persistent infection with relapsing fever borrelias causes significant loss of cardiomyocytes associated with prominent infiltration by activated macrophages, upregulation of IL-6, induction of caspase-1, and apoptosis. PMID:16239571

  6. The bba64 gene of Borrelia burgdorferi, the Lyme disease agent, is critical for mammalian infection via tick bite transmission.

    PubMed

    Gilmore, Robert D; Howison, Rebekah R; Dietrich, Gabrielle; Patton, Toni G; Clifton, Dawn R; Carroll, James A

    2010-04-20

    The spirochetal agent of Lyme disease, Borrelia burgdorferi, is transmitted by bites of Ixodes ticks to mammalian reservoir hosts and humans. The mechanism(s) by which the organism is trafficked from vector to host is poorly understood. In this study, we demonstrate that a B. burgdorferi mutant strain deficient in the synthesis of the bba64 gene product was incapable of infecting mice via tick bite even though the mutant was (i) infectious in mice when introduced by needle inoculation, (ii) acquired by larval ticks feeding on infected mice, and (iii) able to persist through tick molting stages. This finding of a B. burgdorferi gene required for pathogen transfer and/or survival from the tick to the susceptible host represents an important breakthrough toward understanding transmission mechanisms involved for the Lyme disease agent.

  7. [Yellow fever].

    PubMed

    Sabbatani, Sergio; Fiorino, Sirio

    2007-06-01

    After the discovery of the New World, yellow fever proved to be an important risk factor of morbidity and mortality for Caribbean populations. In the following centuries epidemic risk, expanded by sea trade and travel, progressively reached the settlements in North America and Brazil as well as the Atlantic seaboard of tropical and equatorial Africa. In the eighteenth century and the first half of the nineteenth century epidemics of yellow fever were reported in some coastal towns in the Iberian peninsula, French coast, Great Britain and Italy, where, in 1804 at Leghorn, only one epidemic was documented. Prevention and control programs against yellow fever, developed at the beginning of the twentieth century in Cuba and in Panama, were a major breakthrough in understanding definitively its aetiology and pathogenesis. Subsequently, further advances in knowledge of yellow fever epidemiology were obtained when French scientists, working in West and Central Africa, showed that monkeys were major hosts of the yellow fever virus (the wild yellow fever virus), besides man. In addition, advances in research, contributing to the development of vaccines against the yellow fever virus in the first half of the nineteenth century, are reported in this paper. PMID:17599002

  8. Multilocus sequence analysis of Borrelia bissettii strains from North America reveals a new Borrelia species, Borrelia kurtenbachii

    PubMed Central

    Margos, Gabriele; Hojgaard, Andrias; Lane, Robert S.; Cornet, Muriel; Fingerle, Volker; Rudenko, Nataliia; Ogden, Nicholas; Aanensen, David M.; Fish, Durland; Piesman, Joseph

    2010-01-01

    Using multilocus sequence analyses (MLSA), we investigated the phylogenetic relationship of spirochaete strains from North America previously assigned to the genospecies Borrelia bissettii. We amplified internal fragments of 8 housekeeping genes (clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA) located on the main linear chromosome by polymerase chain reaction. Phylogenetic analysis of concatenated sequences of the 8 loci showed that the B. bissettii clade consisted of 4 closely related clusters which included strains from California (including the type strain DN127-Cl9-2/p7) and Colorado that were isolated from Ixodes pacificus, I. spinipalpis, or infected reservoir hosts. Several strains isolated from I. scapularis clustered distantly from B. bissettii. Genetic distance analyses confirmed that these strains are more distant to B. bissettii than they are to B. carolinensis, a recently described Borrelia species, which suggests that they constitute a new Borrelia genospecies. We propose that it be named Borrelia kurtenbachii sp. nov. in honour of the late Klaus Kurtenbach. The data suggest that ecological differences between B. bissettii and the new Borrelia genospecies reflect different transmission cycles. In view of these findings, the distinct vertebrate host-tick vector associations and the distributions of B. bissettii and B. kurtenbachii require further investigation. PMID:21157575

  9. Q Fever.

    PubMed

    Shishido, Akira A; Letiaia, Andrew G; Hartzell, Joshua D

    2016-01-01

    Q fever is a significant infectious disease threat to US military personnel deployed in the Middle East. Its environmental stability, aerosol transmission, and animal reservoir make it a considerable risk for deployed troops due to its potential for weaponization and risk of natural infection. It presents as a flu-like illness that responds promptly to antimicrobial therapy. Q fever should be suspected in patients presenting with a compatible febrile illness in an endemic area and especially if the individual has been exposed to livestock. Diagnosis is confirmed with serologic blood tests, but empiric therapy should be initiated when Q fever is considered. If left untreated, patients with acute Q fever can develop severe complications as well as chronic disease manifesting several months after the initial infection.

  10. Rheumatic Fever

    MedlinePlus

    ... always tell your doctor or dentist about your history of rheumatic fever before you have a surgical or dental procedure. Such procedures may cause bacteria to enter the bloodstream and infect your heart ...

  11. Q Fever.

    PubMed

    Shishido, Akira A; Letiaia, Andrew G; Hartzell, Joshua D

    2016-01-01

    Q fever is a significant infectious disease threat to US military personnel deployed in the Middle East. Its environmental stability, aerosol transmission, and animal reservoir make it a considerable risk for deployed troops due to its potential for weaponization and risk of natural infection. It presents as a flu-like illness that responds promptly to antimicrobial therapy. Q fever should be suspected in patients presenting with a compatible febrile illness in an endemic area and especially if the individual has been exposed to livestock. Diagnosis is confirmed with serologic blood tests, but empiric therapy should be initiated when Q fever is considered. If left untreated, patients with acute Q fever can develop severe complications as well as chronic disease manifesting several months after the initial infection. PMID:26874100

  12. Lassa Fever

    MedlinePlus

    ... an acute viral illness that occurs in west Africa. The illness was discovered in 1969 when two ... Lassa fever is endemic in parts of west Africa including Sierra Leone, Liberia, Guinea and Nigeria; however, ...

  13. Dengue fever.

    PubMed

    Payling, K J

    1997-04-01

    Dengue fever, and its more serious haemorrhagic form, is increasingly being found among UK travellers to tropical and sub-tropical countries. This Update examines transmission, the main symptoms and nursing care of affected people.

  14. Dengue fever

    MedlinePlus

    ... and netting can help reduce the risk of mosquito bites that can spread dengue fever and other infections. Limit outdoor activity during mosquito season, especially when they are most active, at ...

  15. Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model

    PubMed Central

    Wagemakers, Alex; van ‘t Veer, Cornelis; Oei, Anneke; van der Pot, Wouter J.; Ahmed, Kalam; van der Poll, Tom; Geijtenbeek, Teunis B. H.; Hovius, Joppe W. R.

    2016-01-01

    Borrelia burgdorferi is transmitted into the skin of the host where it encounters and interacts with two dendritic cell (DC) subsets; Langerhans cells (LCs) and dermal DCs (DDCs). These cells recognize pathogens via pattern recognition receptors, mature and migrate out of the skin into draining lymph nodes, where they orchestrate adaptive immune responses. In order to investigate the response of skin DCs during the early immunopathogenesis of Lyme borreliosis, we injected B. burgdorferi intradermally into full-thickness human skin and studied the migration of DCs out of the skin, the activation profile and phenotype of migrated cells. We found a significant increase in the migration of LCs and DDCs in response to B. burgdorferi. Notably, migration was prevented by blocking TLR2. DCs migrated from skin inoculated with higher numbers of spirochetes expressed significantly higher levels of CD83 and produced pro-inflammatory cytokines. No difference was observed in the expression of HLA-DR, CD86, CD38, or CCR7. To conclude, we have established an ex vivo human skin model to study DC-B. burgdorferi interactions. Using this model, we have demonstrated that B. burgdorferi-induced DC migration is mediated by TLR2. Our findings underscore the utility of this model as a valuable tool to study immunity to spirochetal infections. PMID:27695100

  16. Treponema pallidum Lipoprotein TP0435 Expressed in Borrelia burgdorferi Produces Multiple Surface/Periplasmic Isoforms and mediates Adherence

    PubMed Central

    Chan, Kamfai; Nasereddin, Thayer; Alter, Laura; Centurion-Lara, Arturo; Giacani, Lorenzo; Parveen, Nikhat

    2016-01-01

    The ability of Treponema pallidum, the syphilis spirochete to colonize various tissues requires the presence of surface-exposed adhesins that have been difficult to identify due to the inability to culture and genetically manipulate T. pallidum. Using a Borrelia burgdorferi-based heterologous system and gain-in-function approach, we show for the first time that a highly immunogenic lipoprotein TP0435 can be differentially processed into multiple isoforms with one variant stochastically displayed on the spirochete surface. TP0435 was previously believed to be exclusively located in T. pallidum periplasm. Furthermore, non-adherent B. burgdorferi strain expressing TP0435 acquires the ability to bind to a variety of host cells including placental cells and exhibits slow opsonophagocytosis in vitro similar to poor ex vivo phagocytosis of T. pallidum by host macrophages reported previously. This phenomenon of production of both surface and periplasmic immunogenic lipoprotein isoforms has possible implications in immune evasion of the obligate pathogen T. pallidum during infection. PMID:27161310

  17. Q Fever

    PubMed Central

    Maurin, M.; Raoult, D.

    1999-01-01

    Q fever is a zoonosis with a worldwide distribution with the exception of New Zealand. The disease is caused by Coxiella burnetii, a strictly intracellular, gram-negative bacterium. Many species of mammals, birds, and ticks are reservoirs of C. burnetii in nature. C. burnetii infection is most often latent in animals, with persistent shedding of bacteria into the environment. However, in females intermittent high-level shedding occurs at the time of parturition, with millions of bacteria being released per gram of placenta. Humans are usually infected by contaminated aerosols from domestic animals, particularly after contact with parturient females and their birth products. Although often asymptomatic, Q fever may manifest in humans as an acute disease (mainly as a self-limited febrile illness, pneumonia, or hepatitis) or as a chronic disease (mainly endocarditis), especially in patients with previous valvulopathy and to a lesser extent in immunocompromised hosts and in pregnant women. Specific diagnosis of Q fever remains based upon serology. Immunoglobulin M (IgM) and IgG antiphase II antibodies are detected 2 to 3 weeks after infection with C. burnetii, whereas the presence of IgG antiphase I C. burnetii antibodies at titers of ≥1:800 by microimmunofluorescence is indicative of chronic Q fever. The tetracyclines are still considered the mainstay of antibiotic therapy of acute Q fever, whereas antibiotic combinations administered over prolonged periods are necessary to prevent relapses in Q fever endocarditis patients. Although the protective role of Q fever vaccination with whole-cell extracts has been established, the population which should be primarily vaccinated remains to be clearly identified. Vaccination should probably be considered in the population at high risk for Q fever endocarditis. PMID:10515901

  18. Ecology of Borrelia burgdorferi in ticks (Acari: Ixodidae), rodents, and birds in the Sierra Nevada foothills, Placer County, California.

    PubMed

    Wright, S A; Thompson, M A; Miller, M J; Knerl, K M; Elms, S L; Karpowicz, J C; Young, J F; Kramer, V L

    2000-11-01

    This study examined the prevalence of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner in host-seeking adult and nymphal Ixodes pacificus Cooley & Kohls and estimated the I. pacificus infestation and B. burgdorferi infection of rodent and avian hosts in the western Sierra Nevada foothills of northern California. Additionally, we identified species likely to participate in an enzootic cycle for B. burgdorferi in this yellow pine transition habitat. Evidence of infection with B. burgdorferi was identified in 7.3 and 5.4% of host-seeking I. pacificus adults and nymphs, respectively. Mean numbers of I. pacificus observed on rodents were 1.15 for Neotoma fuscipes Baird and 0.18 for Peromyscus spp. One of 104 ear punch tissues obtained from woodrats and none from 49 Peromyscus spp. yielded B. burgdorferi. A total of 291 collected birds representing 34 species had a mean of 0.27 I. pacificus per bird. The mean I. pacificus infestation of ground-dwelling birds was 2.5 ticks per bird. Forty-nine of 92 (53%) blood smears collected from birds were reactive to a B. burgdorferi specific antibody. This study presents the identification of a B. burgdorferi-like spirochete in birds in western North America. The tick burden and spirochete infection of birds suggests that birds may be involved in a local B. burgdorferi enzootic cycle and likely participate in the transport of ticks and spirochetes to other locations while rodents from this site do not appear to be major contributors. PMID:11126549

  19. Differential regulation of the multiple flagellins in spirochetes.

    PubMed

    Li, Chunhao; Sal, Melanie; Marko, Michael; Charon, Nyles W

    2010-05-01

    The expression of flagellin genes in most bacteria is typically regulated by the flagellum-specific sigma(28) factor FliA, and an anti-sigma(28) factor, FlgM. However, the regulatory hierarchy in several bacteria that have multiple flagellins is more complex. In these bacteria, the flagellin genes are often transcribed by at least two different sigma factors. The flagellar filament in spirochetes consists of one to three FlaB core proteins and at least one FlaA sheath protein. Here, the genetically amenable bacterium Brachyspira hyodysenteriae was used as a model spirochete to investigate the regulation of its four flagellin genes, flaA, flaB1, flaB2, and flaB3. We found that the flaB1 and flaB2 genes are regulated by sigma(28), whereas the flaA and flaB3 genes are controlled by sigma(70). The analysis of a flagellar motor switch fliG mutant further supported this proposition; in the mutant, the transcription of flaB1 and flaB2 was inhibited, but that of flaA and flaB3 was not. In addition, the continued expression of flaA and flaB3 in the mutant resulted in the formation of incomplete flagellar filaments that were hollow tubes and consisted primarily of FlaA. Finally, our recent studies have shown that each flagellin unit contributes to the stiffness of the periplasmic flagella, and this stiffness directly correlates with motility. The regulatory mechanism identified here should allow spirochetes to change the relative ratio of these flagellin proteins and, concomitantly, vary the stiffness of their flagellar filament.

  20. Historic evidence to support a causal relationship between spirochetal infections and Alzheimer’s disease

    PubMed Central

    Miklossy, Judith

    2015-01-01

    Following previous observations a statistically significant association between various types of spirochetes and Alzheimer’s disease (AD) fulfilled Hill’s criteria in favor of a causal relationship. If spirochetal infections can indeed cause AD, the pathological and biological hallmarks of AD should also occur in syphilitic dementia. To answer this question, observations and illustrations on the detection of spirochetes in the atrophic form of general paresis, which is known to be associated with slowly progressive dementia, were reviewed and compared with the characteristic pathology of AD. Historic observations and illustrations published in the first half of the 20th Century indeed confirm that the pathological hallmarks, which define AD, are also present in syphilitic dementia. Cortical spirochetal colonies are made up by innumerable tightly spiraled Treponema pallidum spirochetes, which are morphologically indistinguishable from senile plaques, using conventional light microscopy. Local brain amyloidosis also occurs in general paresis and, as in AD, corresponds to amyloid beta. These historic observations enable us to conclude that chronic spirochetal infections can cause dementia and reproduce the defining hallmarks of AD. They represent further evidence in support a causal relationship between various spirochetal infections and AD. They also indicate that local invasion of the brain by these helically shaped bacteria reproduce the filamentous pathology characteristic of AD. Chronic infection by spirochetes, and co-infection with other bacteria and viruses should be included in our current view on the etiology of AD. Prompt action is needed as AD might be prevented. PMID:25932012

  1. Genetic diversity of Borrelia burgdorferi sensu stricto in Peromyscus leucopus, the primary reservoir of Lyme disease in a region of endemicity in southern Maryland.

    PubMed

    Anderson, Jennifer M; Norris, Douglas E

    2006-08-01

    In the north central and northeastern United States, Borrelia burgdorferi sensu stricto, the etiologic agent of Lyme disease (LD), is maintained in an enzootic cycle between the vector, Ixodes scapularis, and the primary reservoir host, Peromyscus leucopus. Genetic diversity of the pathogen based on sequencing of two plasmid-located genes, those for outer surface protein A (ospA) and outer surface protein C (ospC), has been examined in both tick and human specimens at local, regional, and worldwide population scales. Additionally, previous studies have only been conducted with tick or human specimens at the local population level in areas with high LD transmission rates. This study examined the genetic diversity of circulating borreliae in the reservoir population from a large region of the western coastal plains of southern Maryland, where moderate numbers of human LD cases are reported. Six ospA mobility classes, including two that were not previously described, and eight ospC groups were found among the P. leucopus samples. Twenty-five percent of all specimens were infected with more than one ospA or ospC variant. The frequency distribution of variants was homogeneous, both locally and spatially. The spirochete diversity found in Maryland was not as high as that observed among northern tick populations, yet similar genotypes were observed in both populations. These results also show that mice are important for maintaining Borrelia variants, even rare variants, and that reservoir populations should therefore be considered when assessing the diversity of B. burgdorferi.

  2. Functional Equivalence of OspA and OspB, but Not OspC, in Tick Colonization by Borrelia burgdorferi

    PubMed Central

    Bestor, Aaron

    2016-01-01

    Borrelia burgdorferi, a Lyme disease agent, makes different major outer surface lipoproteins at different stages of its mouse–tick infectious cycle. Outer surface protein A (OspA) coats the spirochetes from the time they enter ticks until they are transmitted to a mammal. OspA is required for normal tick colonization and has been shown to bind a tick midgut protein, indicating that OspA may serve as a tick midgut adhesin. Tick colonization by spirochetes lacking OspA is increased when the infecting blood meal is derived from mice that do not produce antibody, indicating that OspA may protect the spirochetes from host antibody, which will not recognize tick-specific proteins such as OspA. To further study the importance of OspA during tick colonization, we constructed a form of B. burgdorferi in which the ospA open reading frame, on lp54, was replaced with the ospC gene or the ospB gene, encoding a mammal-specific or tick-specific lipoprotein, respectively. These fusions yielded a strain that produces OspC within a tick (from the fusion gene) and during early mammalian infection (from the normal ospC locus) and a strain that produces OspB in place of OspA within ticks. Here we show that the related, tick-specific protein OspB can fully substitute for OspA, whereas the unrelated, mammal-specific protein OspC cannot. These data were derived from three different methods of infecting ticks, and they confirm and extend previous studies indicating that OspA both protects spirochetes within ticks from mammalian antibody and serves an additional role during tick colonization. PMID:26953324

  3. Transmission cycles of Borrelia burgdorferi and B. bissettii in relation to habitat type in northwestern California.

    PubMed

    Eisen, Lars; Eisen, Rebecca J; Mun, Jeomhee; Salkeld, Daniel J; Lane, Robert S

    2009-06-01

    This study was undertaken to determine which rodent species serve as primary reservoirs for the Lyme disease spirochete Borrelia burgdorferi in commonly occurring woodland types in inland areas of northwestern California, and to examine whether chaparral or grassland serve as source habitats for dispersal of B. burgdorferi- or B. bissettii-infected rodents into adjacent woodlands. The western gray squirrel (Sciurus griseus) was commonly infected with B. burgdorferi in oak woodlands, whereas examination of 30 dusky-footed woodrats (Neotoma fuscipes) and 280 Peromyscus spp. mice from 13 widely spaced Mendocino County woodlands during 2002 and 2003 yielded only one infected woodrat and one infected deer mouse (P. maniculatus). These data suggest that western gray squirrels account for the majority of production by rodents of fed Ixodes pacificus larvae infected with B. burgdorferi in the woodlands sampled. Infections with B. burgdorferi also were rare in woodrats (0/47, 0/3) and mice (3/66, 1/6) captured in chaparral and grassland, respectively, and therefore these habitats are unlikely sources for dispersal of this spirochete into adjacent woodlands. On the other hand, B. bissettii was commonly detected in both woodrats (22/47) and mice (15/66) in chaparral. We conclude that the data from this and previous studies in northwestern California are suggestive of a pattern where inland oak-woodland habitats harbor a B. burgdorferi transmission cycle driven primarily by I. pacificus and western gray squirrels, whereas chaparral habitats contain a B. bissettii transmission cycle perpetuated largely by I. spinipalpis, woodrats and Peromyscus mice. The dominant role of western gray squirrels as reservoirs of B. burgdorferi in certain woodlands offers intriguing opportunities for preventing Lyme disease by targeting these animals by means of either host-targeted acaricides or oral vaccination against B. burgdorferi. PMID:20514140

  4. Birds and their ticks in northwestern California: minimal contribution to Borrelia burgdorferi enzootiology.

    PubMed

    Slowik, T J; Lane, R S

    2001-08-01

    Birds and their attendant ticks were surveyed for infection with the Lyme disease spirochete Borrelia burgdorferi, in chaparral and woodland-grass habitats in northwestern California from March to July, 1998 to 1999. In total, 234 birds were captured and recaptured (15%); nearly 2.5 times more birds were captured in chaparral than in woodland-grass. Overall, 34 species representing 15 families were collected during this study; of these, 24 species were caught in chaparral, 19 in woodland-grass, and 9 in both vegetational types. The most frequently captured birds were sage sparrows (Amphispiza belli) in chaparral, and American robins (Turdus migratorius) and oak titmice (Baelophus inornatus) in woodland-grass. Birds hosted 35 Ixodes pacificus (15 larvae, 20 nymphs) and 9 Haemaphysalis leporispalustris (3 larvae, 5 nymphs, 1 adult) ticks, of which 32 were removed from chaparral birds and 12 from woodland birds. The prevalence of tick infestation was 13% (21/167) in chaparral and 5% (3/67) in woodland-grass, but the relative and mean tick intensities of 0.19 and 1.5 for chaparral birds, and 0.18 and 4.0 for woodland birds, respectively, did not differ significantly by habitat. Spirochetes were not detected in either bird-blood or tick-tissue samples when tested by culture, immunofluorescence, or Giemsa-staining. In contrast, over 90% (86/94) of western fence lizards (Sceloporus occidentalis) collected in June or July were infested with an average of 6.9 and 8.9 immature I. pacificus in chaparral and woodland-grass, respectively. We conclude that birds contribute little to the enzootiology of B. burgdorferi in chaparral and woodland-grass habitats in northwestern California because of their limited parasitism by tick vectors and lack of detectable spirochetemias. PMID:11534638

  5. Borrelia burgdorferi swims with a planar waveform similar to that of eukaryotic flagella.

    PubMed Central

    Goldstein, S F; Charon, N W; Kreiling, J A

    1994-01-01

    Borrelia burgdorferi is a motile spirochete with multiple internal periplasmic flagella (PFs) attached near each end of the cell cylinder; these PFs overlap in the cell center. We analyzed the shape and motion of wild type and PF-deficient mutants using both photomicrography and video microscopy. We found that swimming cells resembled the dynamic movements of eukaryotic flagella. In contrast to helically shaped spirochetes, which propagate spiral waves, translating B. burgdorferi swam with a planar waveform with occasional axial twists; waves had a peak-to-peak amplitude of 0.85 micron and a wavelength of 3.19 microns. Planar waves began full-sized at the anterior end and propagated toward the back end of the cell. Concomitantly, these waves gyrated counter-clockwise as viewed from the posterior end along the cell axis. In nontranslating cells, wave propagation ceased. Either the waveform of nontranslating cells resembled the translating form, or the cells became markedly contorted. Cells of the PF-deficient mutant isolated by Sadziene et al. [Sadziene, A., Thomas, D. D., Bundoc, V. G., Holt, S. C. & Barbour, A. G. (1991) J. Clin. Invest. 88, 82-92] were found to be relatively straight. The results suggest that the shape of B. burgdorferi is dictated by interactions between the cell body and the PFs. In addition, the PFs from opposite ends of the cell are believed to interact with one another so that during the markedly distorted nontranslational form, the PFs from opposite ends rotate in opposing directions around one another, causing the cell to bend. Images PMID:8159765

  6. Transmission cycles of Borrelia burgdorferi and B. bissettii in relation to habitat type in northwestern California

    PubMed Central

    Eisen, Lars; Eisen, Rebecca J.; Mun, Jeomhee; Salkeld, Daniel J.; Lane, Robert S.

    2008-01-01

    This study was undertaken to determine which rodent species serve as primary reservoirs for the Lyme disease spirochete Borrelia burgdorferi in commonly occurring woodland types in inland areas of northwestern California, and to examine whether chaparral or grassland serve as source habitats for dispersal of B. burgdorferi- or B. bissettii-infected rodents into adjacent woodlands. The western gray squirrel (Sciurus griseus) was commonly infected with B. burgdorferi in oak woodlands, whereas examination of 30 dusky-footed woodrats (Neotoma fuscipes) and 280 Peromyscus spp. mice from 13 widely spaced Mendocino County woodlands during 2002 and 2003 yielded only one infected woodrat and one infected deer mouse (P. maniculatus). These data suggest that western gray squirrels account for the majority of production by rodents of fed Ixodes pacificus larvae infected with B. burgdorferi in the woodlands sampled. Infections with B. burgdorferi also were rare in woodrats (0/47, 0/3) and mice (3/66, 1/6) captured in chaparral and grassland, respectively, and therefore these habitats are unlikely sources for dispersal of this spirochete into adjacent woodlands. On the other hand, B. bissettii was commonly detected in both woodrats (22/47) and mice (15/66) in chaparral. We conclude that the data from this and previous studies in northwestern California are suggestive of a pattern where inland oak-woodland habitats harbor a B. burgdorferi transmission cycle driven primarily by I. pacificus and western gray squirrels, whereas chaparral habitats contain a B. bissettii transmission cycle perpetuated largely by I. spinipalpis, woodrats and Peromyscus mice. The dominant role of western gray squirrels as reservoirs of B. burgdorferi in certain woodlands offers intriguing opportunities for preventing Lyme disease by targeting these animals by means of either host-targeted acaricides or oral vaccination against B. burgdorferi. PMID:20514140

  7. Borrelia burgdorferi swims with a planar waveform similar to that of eukaryotic flagella.

    PubMed

    Goldstein, S F; Charon, N W; Kreiling, J A

    1994-04-12

    Borrelia burgdorferi is a motile spirochete with multiple internal periplasmic flagella (PFs) attached near each end of the cell cylinder; these PFs overlap in the cell center. We analyzed the shape and motion of wild type and PF-deficient mutants using both photomicrography and video microscopy. We found that swimming cells resembled the dynamic movements of eukaryotic flagella. In contrast to helically shaped spirochetes, which propagate spiral waves, translating B. burgdorferi swam with a planar waveform with occasional axial twists; waves had a peak-to-peak amplitude of 0.85 micron and a wavelength of 3.19 microns. Planar waves began full-sized at the anterior end and propagated toward the back end of the cell. Concomitantly, these waves gyrated counter-clockwise as viewed from the posterior end along the cell axis. In nontranslating cells, wave propagation ceased. Either the waveform of nontranslating cells resembled the translating form, or the cells became markedly contorted. Cells of the PF-deficient mutant isolated by Sadziene et al. [Sadziene, A., Thomas, D. D., Bundoc, V. G., Holt, S. C. & Barbour, A. G. (1991) J. Clin. Invest. 88, 82-92] were found to be relatively straight. The results suggest that the shape of B. burgdorferi is dictated by interactions between the cell body and the PFs. In addition, the PFs from opposite ends of the cell are believed to interact with one another so that during the markedly distorted nontranslational form, the PFs from opposite ends rotate in opposing directions around one another, causing the cell to bend.

  8. Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen, Borrelia burgdorferi.

    PubMed Central

    Schoenfeld, R; Araneo, B; Ma, Y; Yang, L M; Weis, J J

    1992-01-01

    Lyme disease refers to the multisymptomatic illness in humans which results from infection with the tick-borne spirochete Borrelia burgdorferi. The white-footed mouse is the major reservoir for B. burgdorferi and, upon infection, certain inbred mice develop symptoms similar to those reported in human disease. Sonicated preparations of washed spirochetes were found to have potent mitogenic activity when cultured with lymphocytes from naive C57BL/6, C3H/HeJ, or BALB/c mice. The activity of the B. burgdorferi sonicate was approximately fourfold greater than that of a similarly prepared Escherichia coli sonicate. Polymyxin B efficiently inhibited the mitogenic activity of the E. coli sonicate but only slightly inhibited that of the B. burgdorferi sonicate, suggesting that a lipid A-containing lipopolysaccharide was not responsible for the B. burgdorferi activity. Kinetic analysis indicated peak proliferation at 2 to 3 days of culturing, suggesting polyclonal activation. B- and T-lymphocyte depletion experiments indicated that the major cell type responding to the B. burgdorferi mitogen was the B lymphocyte. This mitogen stimulated murine B cells not only to proliferate but also to differentiate into antibody-secreting cells, as demonstrated by the production of immunoglobulin by stimulated splenocytes. Furthermore, the sonicated preparation stimulated the B-cell tumor line CH12.LX to secrete immunoglobulin in the absence of accessory cells. B. burgdorferi also stimulated interleukin-6 production in splenocyte cultures. The observation that B. burgdorferi can stimulate activation of and immunoglobulin production by normal B lymphocytes may directly reflect on the development of arthritis associated with persistent infection by this organism. Images PMID:1730476

  9. Transmission cycles of Borrelia burgdorferi and B. bissettii in relation to habitat type in northwestern California.

    PubMed

    Eisen, Lars; Eisen, Rebecca J; Mun, Jeomhee; Salkeld, Daniel J; Lane, Robert S

    2009-06-01

    This study was undertaken to determine which rodent species serve as primary reservoirs for the Lyme disease spirochete Borrelia burgdorferi in commonly occurring woodland types in inland areas of northwestern California, and to examine whether chaparral or grassland serve as source habitats for dispersal of B. burgdorferi- or B. bissettii-infected rodents into adjacent woodlands. The western gray squirrel (Sciurus griseus) was commonly infected with B. burgdorferi in oak woodlands, whereas examination of 30 dusky-footed woodrats (Neotoma fuscipes) and 280 Peromyscus spp. mice from 13 widely spaced Mendocino County woodlands during 2002 and 2003 yielded only one infected woodrat and one infected deer mouse (P. maniculatus). These data suggest that western gray squirrels account for the majority of production by rodents of fed Ixodes pacificus larvae infected with B. burgdorferi in the woodlands sampled. Infections with B. burgdorferi also were rare in woodrats (0/47, 0/3) and mice (3/66, 1/6) captured in chaparral and grassland, respectively, and therefore these habitats are unlikely sources for dispersal of this spirochete into adjacent woodlands. On the other hand, B. bissettii was commonly detected in both woodrats (22/47) and mice (15/66) in chaparral. We conclude that the data from this and previous studies in northwestern California are suggestive of a pattern where inland oak-woodland habitats harbor a B. burgdorferi transmission cycle driven primarily by I. pacificus and western gray squirrels, whereas chaparral habitats contain a B. bissettii transmission cycle perpetuated largely by I. spinipalpis, woodrats and Peromyscus mice. The dominant role of western gray squirrels as reservoirs of B. burgdorferi in certain woodlands offers intriguing opportunities for preventing Lyme disease by targeting these animals by means of either host-targeted acaricides or oral vaccination against B. burgdorferi.

  10. Reservoir competence of four chaparral-dwelling rodents for Borrelia burgdorferi in California.

    PubMed

    Brown, R N; Lane, R S

    1996-01-01

    Aspects of the reservoir competence of four rodents for the Lyme disease spirochete, Borrelia burgdorferi, were evaluated in California. Rodents were live-trapped and ear-punch biopsies were cultured during each season. A second set of biopsies was cultured from representative individuals after 2-3 weeks of captivity and the results of culturing biopsies taken on both dates were compared with the results of feeding Ixodes pacificus larvae on hosts xenodiagnostically. The prevalence of infections did not differ significantly between dusky-footed woodrats (Neotoma fuscipes) and California kangaroo rats (Dipodomys californicus) nor among seasons. Combined results of the three tests showed that 85.7% of dusky-footed woodrats (n = 21) and 78.6% of California kangaroo rats (n = 14) were infected with B. burgdorferi. In contrast, only 22.2% of brush mice (Peromyscus boylii) (n = 14) and 7.1% of pinyon mice (P. truei) (n = 9) were infected. The sensitivity of culturing ear-punch biopsies as an assay for borrelial infection was significantly greater when biopsies were taken after a short period of captivity (0.89) rather than on the day of capture (0.52). Tick xenodiagnosis, in which I. pacificus was used as the vector, revealed borrelial infections in 90.3% of infected rodents. Spirochetes were observed in 37.7% of 239, 45.2% of 155, 60.0% of 10, and 7.1% of 14 cultures of nymphal I. pacificus fed as larvae on naturally infected woodrats, kangaroo rats, brush mice, and a pinyon mouse, respectively. The mean prevalence of infection in xenodiagnostic ticks varied significantly among host species with a greater proportion of ticks infected while feeding on woodrats and kangaroo rats than on mice. This study reconfirms previous reports that implicated woodrats and kangaroo rats as reservoirs of B. burgdorferi in California.

  11. Birds and their ticks in northwestern California: minimal contribution to Borrelia burgdorferi enzootiology.

    PubMed

    Slowik, T J; Lane, R S

    2001-08-01

    Birds and their attendant ticks were surveyed for infection with the Lyme disease spirochete Borrelia burgdorferi, in chaparral and woodland-grass habitats in northwestern California from March to July, 1998 to 1999. In total, 234 birds were captured and recaptured (15%); nearly 2.5 times more birds were captured in chaparral than in woodland-grass. Overall, 34 species representing 15 families were collected during this study; of these, 24 species were caught in chaparral, 19 in woodland-grass, and 9 in both vegetational types. The most frequently captured birds were sage sparrows (Amphispiza belli) in chaparral, and American robins (Turdus migratorius) and oak titmice (Baelophus inornatus) in woodland-grass. Birds hosted 35 Ixodes pacificus (15 larvae, 20 nymphs) and 9 Haemaphysalis leporispalustris (3 larvae, 5 nymphs, 1 adult) ticks, of which 32 were removed from chaparral birds and 12 from woodland birds. The prevalence of tick infestation was 13% (21/167) in chaparral and 5% (3/67) in woodland-grass, but the relative and mean tick intensities of 0.19 and 1.5 for chaparral birds, and 0.18 and 4.0 for woodland birds, respectively, did not differ significantly by habitat. Spirochetes were not detected in either bird-blood or tick-tissue samples when tested by culture, immunofluorescence, or Giemsa-staining. In contrast, over 90% (86/94) of western fence lizards (Sceloporus occidentalis) collected in June or July were infested with an average of 6.9 and 8.9 immature I. pacificus in chaparral and woodland-grass, respectively. We conclude that birds contribute little to the enzootiology of B. burgdorferi in chaparral and woodland-grass habitats in northwestern California because of their limited parasitism by tick vectors and lack of detectable spirochetemias.

  12. Xenodiagnosis to Detect Borrelia burgdorferi Infection: A First-in-Human Study

    PubMed Central

    Marques, Adriana; Telford, Sam R.; Turk, Siu-Ping; Chung, Erin; Williams, Carla; Dardick, Kenneth; Krause, Peter J.; Brandeburg, Christina; Crowder, Christopher D.; Carolan, Heather E.; Eshoo, Mark W.; Shaw, Pamela A.; Hu, Linden T.

    2014-01-01

    Background. Animal studies suggest that Borrelia burgdorferi, the agent of Lyme disease, may persist after antibiotic therapy and can be detected by various means including xenodiagnosis using the natural tick vector (Ixodes scapularis). No convincing evidence exists for the persistence of viable spirochetes after recommended courses of antibiotic therapy in humans. We determined the safety of using I. scapularis larvae for the xenodiagnosis of B. burgdorferi infection in humans. Methods. Laboratory-reared larval I. scapularis ticks were placed on 36 subjects and allowed to feed to repletion. Ticks were tested for B. burgdorferi by polymerase chain reaction (PCR), culture, and/or isothermal amplification followed by PCR and electrospray ionization mass spectroscopy. In addition, attempts were made to infect immunodeficient mice by tick bite or inoculation of tick contents. Xenodiagnosis was repeated in 7 individuals. Results. Xenodiagnosis was well tolerated with no severe adverse events. The most common adverse event was mild itching at the tick attachment site. Xenodiagnosis was negative in 16 patients with posttreatment Lyme disease syndrome (PTLDS) and/or high C6 antibody levels and in 5 patients after completing antibiotic therapy for erythema migrans. Xenodiagnosis was positive for B. burgdorferi DNA in a patient with erythema migrans early during therapy and in a patient with PTLDS. There is insufficient evidence, however, to conclude that viable spirochetes were present in either patient. Conclusions. Xenodiagnosis using Ixodes scapularis larvae was safe and well tolerated. Further studies are needed to determine the sensitivity of xenodiagnosis in patients with Lyme disease and the significance of a positive result. Clinical Trials Registration NCT01143558. PMID:24523212

  13. Comparative analysis of the Borrelia garinii genome.

    PubMed

    Glöckner, G; Lehmann, R; Romualdi, A; Pradella, S; Schulte-Spechtel, U; Schilhabel, M; Wilske, B; Sühnel, J; Platzer, M

    2004-01-01

    Three members of the genus Borrelia (B.burgdorferi, B.garinii, B.afzelii) cause tick-borne borreliosis. Depending on the Borrelia species involved, the borreliosis differs in its clinical symptoms. Comparative genomics opens up a way to elucidate the underlying differences in Borrelia species. We analysed a low redundancy whole-genome shotgun (WGS) assembly of a B.garinii strain isolated from a patient with neuroborreliosis in comparison to the B.burgdorferi genome. This analysis reveals that most of the chromosome is conserved (92.7% identity on DNA as well as on amino acid level) in the two species, and no chromosomal rearrangement or larger insertions/deletions could be observed. Furthermore, two collinear plasmids (lp54 and cp26) seem to belong to the basic genome inventory of Borrelia species. These three collinear parts of the Borrelia genome encode 861 genes, which are orthologous in the two species examined. The majority of the genetic information of the other plasmids of B.burgdorferii is also present in B.garinii although orthology is not easy to define due to a high redundancy of the plasmid fraction. Yet, we did not find counterparts of the B.burgdorferi plasmids lp36 and lp38 or their respective gene repertoire in the B.garinii genome. Thus, phenotypic differences between the two species could be attributable to the presence or absence of these two plasmids as well as to the potentially positively selected genes. PMID:15547252

  14. Geographical distribution and prevalence of Borrelia burgdorferi genospecies in questing Ixodes ricinus from Romania: a countrywide study.

    PubMed

    Kalmár, Zsuzsa; Mihalca, Andrei D; Dumitrache, Mirabela O; Gherman, Călin M; Magdaş, Cristian; Mircean, Viorica; Oltean, Miruna; Domşa, Cristian; Matei, Ioana A; Mărcuţan, Daniel I; Sándor, Attila D; D'Amico, Gianluca; Paştiu, Anamaria; Györke, Adriana; Gavrea, Raluca; Marosi, Béla; Ionică, Angela; Burkhardt, Etelka; Toriay, Hortenzia; Cozma, Vasile

    2013-09-01

    The paper reports the prevalence and geographical distribution of Borrelia burgdorferi sensu lato (s.l.) and its genospecies in 12,221 questing Ixodes ricinus ticks collected at 183 locations from all the 41 counties of Romania. The unfed ticks were examined for the presence of B. burgdorferi s.l. by PCR targeting the intergenic spacer 5S-23S. Reverse line blot hybridization (RLB) and restriction fragment length polymorphism (RFLP) analysis were performed for identification of B. burgdorferi genospecies. The overall prevalence of infection was 1.4%, with an average local prevalence between 0.75% and 18.8%. B. burgdorferi s.l. was found in ticks of 55 of the 183 localities. The overall prevalence B. burgdorferi s.l. in ticks in the infected localities was 3.8%. The total infection prevalence was higher in female ticks than in other developmental stages. Three Borrelia genospecies were detected. The most widely distributed genospecies was B. afzelii, followed by B. garinii and B. burgdorferi sensu stricto (s.s.). The study is the first countrywide study and the first report of B. burgdorferi s.s. in Romania. The distribution maps show that higher prevalences were recorded in hilly areas, but Lyme borreliosis spirochetes were also present in forested lowlands, albeit with a lower prevalence.

  15. Interleukin-10 Alters Effector Functions of Multiple Genes Induced by Borrelia burgdorferi in Macrophages To Regulate Lyme Disease Inflammation ▿ †

    PubMed Central

    Gautam, Aarti; Dixit, Saurabh; Philipp, Mario T.; Singh, Shree R.; Morici, Lisa A.; Kaushal, Deepak; Dennis, Vida A.

    2011-01-01

    Interleukin-10 (IL-10) modulates inflammatory responses elicited in vitro and in vivo by Borrelia burgdorferi, the Lyme disease spirochete. How IL-10 modulates these inflammatory responses still remains elusive. We hypothesize that IL-10 inhibits effector functions of multiple genes induced by B. burgdorferi in macrophages to control concomitantly elicited inflammation. Because macrophages are essential in the initiation of inflammation, we used mouse J774 macrophages and live B. burgdorferi spirochetes as the model target cell and stimulant, respectively. First, we employed transcriptome profiling to identify genes that were induced by stimulation of cells with live spirochetes and that were perturbed by addition of IL-10 to spirochete cultures. Spirochetes significantly induced upregulation of 347 genes at both the 4-h and 24-h time points. IL-10 inhibited the expression levels, respectively, of 53 and 65 of the 4-h and 24-h genes, and potentiated, respectively, at 4 h and 24 h, 65 and 50 genes. Prominent among the novel identified IL-10-inhibited genes also validated by quantitative real-time PCR (qRT-PCR) were Toll-like receptor 1 (TLR1), TLR2, IRAK3, TRAF1, IRG1, PTGS2, MMP9, IFI44, IFIT1, and CD40. Proteome analysis using a multiplex enzyme-linked immunosorbent assay (ELISA) revealed the IL-10 modulation/and or potentiation of RANTES/CCL5, macrophage inflammatory protein 2 (MIP-2)/CXCL2, IP-10/CXCL10, MIP-1α/CCL3, granulocyte colony-stimulating factor (G-CSF)/CSF3, CXCL1, CXCL5, CCL2, CCL4, IL-6, tumor necrosis factor alpha (TNF-α), IL-1α, IL-1β, gamma interferon (IFN-γ), and IL-9. Similar results were obtained using sonicated spirochetes or lipoprotein as stimulants. Our data show that IL-10 alters effectors induced by B. burgdorferi in macrophages to control concomitantly elicited inflammatory responses. Moreover, for the first time, this study provides global insight into potential mechanisms used by IL-10 to control Lyme disease inflammation. PMID

  16. Relapsing fever borreliosis in Eurasia--forgotten, but certainly not gone!

    PubMed

    Assous, M V; Wilamowski, A

    2009-05-01

    Tick-borne relapsing fever (TBRF) has been reported in Eurasia and attributed mainly to Borrelia persica, although other entities have also been described. Ornithodoros tholozani is the most important tick vector, found in India and Kashmir, the southern countries of the former USSR, Iran, Iraq, Syria, Jordan, Turkey, Israel, Egypt, and Cyprus. It inhabits caves, ruins, and burrows of rodents and small mammals. In the northern countries, O. tholozani also lives in houses and cowsheds. In Israel, 30-60% of caves were found to be infested. PCR studies of Borrelia infection of O. tholozani ticks collected in caves showed very variable rates, ranging from less than 2% to 40%. The number of human cases reported varies among countries, from eight cases per year in Israel to 72 cases per year in Iran. The incubation period is 5-9 days. The fever attacks last from several hours to 4 days, and are accompanied by chills, headache, nausea and vomiting, sweating, abdominal pain, arthralgia, and cough; complications are rare. Other described Borrelia species are Borrelia caucasica, Borrelia latyschewii, Borrelia microtii, and Borrelia baltazardi. The classic taxonomy based on the co-speciation concept is very complex and very confusing. For this reason, 16S rRNA and flaB genes were used for taxonomic clarification. Sequencing of Israeli TBRF flaB genes, from human and tick samples, has demonstrated a third cluster corresponding to the Eurasia strains, in addition to both New World and Old World clusters. Thin and thick blood smears remain the most frequently used methods for laboratory diagnosis, with a sensitivity of 80%. PCR-based diagnosis is the most sensitive method, and has the advantage of allowing species identification. PMID:19489923

  17. Bpur, the Lyme Disease Spirochete's PUR Domain Protein

    PubMed Central

    Jutras, Brandon L.; Chenail, Alicia M.; Carroll, Dustin W.; Miller, M. Clarke; Zhu, Haining; Bowman, Amy; Stevenson, Brian

    2013-01-01

    The PUR domain is a nucleic acid-binding motif found in critical regulatory proteins of higher eukaryotes and in certain species of bacteria. During investigations into mechanisms by which the Lyme disease spirochete controls synthesis of its Erp surface proteins, it was discovered that the borrelial PUR domain protein, Bpur, binds with high affinity to double-stranded DNA adjacent to the erp transcriptional promoter. Bpur was found to enhance the effects of the erp repressor protein, BpaB. Bpur also bound single-stranded DNA and RNA, with relative affinities RNA > double-stranded DNA > single-stranded DNA. Rational site-directed mutagenesis of Bpur identified amino acid residues and domains critical for interactions with nucleic acids, and it revealed that the PUR domain has a distinct mechanism of interaction with each type of nucleic acid ligand. These data shed light on both gene regulation in the Lyme spirochete and functional mechanisms of the widely distributed PUR domain. PMID:23846702

  18. Life history of Ixodes (Ixodes) jellisoni (Acari: Ixodidae) and its vector competence for Borrelia burgdorferi sensu lato.

    PubMed

    Lane, R S; Peavey, C A; Padgett, K A; Hendson, M

    1999-05-01

    Ixodes (Ixodes) jellisoni Cooley & Kohls, a nonhuman biting and little known tick, is one of 4 members of the I. ricinus complex in the United States. A localized population of I. jellisoni inhabiting a grassland biotope in Mendocino County, CA, was studied from 1993 to 1997. Rodent trapping in all seasons revealed that the only host of both immature and adult I. jellisoni was the heteromyid rodent Dipodomys californicus Merriam. Field investigations suggested that I. jellisoni is nidicolous in habit, and laboratory findings demonstrated that it reproduces parthenogenetically. Known parthenogenetic females (n = 4) produced an average of 530 eggs of which 74% hatched, which was comparable to the fecundity and fertility of wild-caught females (n = 8). After the transstadial molt, 57 F1 or F2 nymphs derived from 2 wild-caught or 4 laboratory-reared, unmated females produced only females. Ixodes jellisoni males were not found on 112 wild-caught D. californicus individuals that were captured an average of 2 times. Collectively, these findings suggest that I. jellisoni may be obligatorily parthenogenetic. Borrelial isolates were obtained from 85% of 58 D. californicus and 33% of 21 I. jellisoni females removed from this rodent. None of the 7 infected female ticks passed borreliae ovarially to its F1 larval progeny. Eight D. californicus and 5 I. jellisoni-derived isolates that were genetically characterized belonged to 2 restriction pattern groups of Borrelia burgdorferi s.l. Neither restriction pattern group has been assigned to a particular genospecies yet. After placement on naturally infected D. californicus, noninfected larval ticks acquired and transstadially passed spirochetes as efficiently as (group 1 borreliae) or 6 times more efficiently (group 2 borreliae) than Ixodes pacificus Cooley & Kohls. As few as 1-4 infected I. jellisoni nymphs were capable of transmitting group 1 or group 2 borreliae to naive D. californicus. We conclude that I. jellisoni is a

  19. Identification and characterization of a surface-exposed, 66-kilodalton protein from Borrelia burgdorferi.

    PubMed Central

    Probert, W S; Allsup, K M; LeFebvre, R B

    1995-01-01

    The surface-exposed antigens of Borrelia burgdorferi represent important targets for the development of a protective immune response. We have identified a proteinase K-accessible, 66-kDa protein from B. burgdorferi and have demonstrated that at least a portion of this protein is surface exposed. The 66-kDa protein was purified by sequential extraction of spirochetes with butanol and Triton X-114 followed by preparative gel electrophoresis. Polyclonal antibodies developed against the purified 66-kDa protein were Borrelia spp. specific, whereas a monoclonal antibody, Route 66, displayed a genospecies-specific pattern of recognition for the 66-kDa protein. N-terminal amino acid sequence was obtained from an internal fragment, a truncated version, and the full-length form of the 66-kDa protein. A search of protein and gene databases for homologous sequences yielded a match with the predicted amino acid sequence from a segment of B. burgdorferi chromosomal DNA (P. A. Rosa, D. Hogan, and T. G. Schwan, J. Clin. Microbiol. 29:524-532, 1991). The construction of primers based on this DNA sequence and the N-terminal amino acid sequence allowed the amplification and cloning of the 66-kDa-protein gene. The identity of the cloned gene was verified by the recognition of the expressed gene product by Route 66. Pulsed-field gel electrophoresis and Southern blot analysis were performed to confirm the chromosomal location of the 66-kDa-protein gene. This study describes the identification and cloning of the first chromosomally encoded, surface-exposed protein from B. burgdoferi. PMID:7729905

  20. Few vertebrate species dominate the Borrelia burgdorferi s.l. life cycle

    NASA Astrophysics Data System (ADS)

    Hofmeester, T. R.; Coipan, E. C.; van Wieren, S. E.; Prins, H. H. T.; Takken, W.; Sprong, H.

    2016-04-01

    Background. In the northern hemisphere, ticks of the Ixodidae family are vectors of diseases such as Lyme borreliosis, Rocky Mountain spotted fever and tick-borne encephalitis. Most of these ticks are generalists and have a three-host life cycle for which they are dependent on three different hosts for their blood meal. Finding out which host species contribute most in maintaining ticks and the pathogens they transmit, is imperative in understanding the drivers behind the dynamics of a disease. Methods. We performed a systematic review to identify the most important vertebrate host species for Ixodes ricinus and Borrelia burgdorferi s.l. as a well-studied model system for tick-borne diseases. We analyzed data from 66 publications and quantified the relative contribution for 15 host species. Review results. We found a positive correlation between host body mass and tick burdens for the different stages of I. ricinus. We show that nymphal burdens of host species are positively correlated with infection prevalence with B. burgdorferi s.l., which is again positively correlated with the realized reservoir competence of a host species for B. burgdorferi s.l. Our quantification method suggests that only a few host species, which are amongst the most widespread species in the environment (rodents, thrushes and deer), feed the majority of I. ricinus individuals and that rodents infect the majority of I. ricinus larvae with B. burgdorferi s.l. Discussion. We argue that small mammal-transmitted Borrelia spp. are maintained due to the high density of their reservoir hosts, while bird-transmitted Borrelia spp. are maintained due to the high infection prevalence of their reservoir hosts. Our findings suggest that Ixodes ricinus and Borrelia burgdorferi s.l. populations are maintained by a few widespread host species. The increase in distribution and abundance of these species, could be the cause for the increase in Lyme borreliosis incidence in Europe in recent decades.

  1. Structural mechanisms underlying sequence-dependent variations in GAG affinities of decorin binding protein A, a Borrelia burgdorferi adhesin.

    PubMed

    Morgan, Ashli M; Wang, Xu

    2015-05-01

    Decorin-binding protein A (DBPA) is an important surface adhesin of the bacterium Borrelia burgdorferi, the causative agent of Lyme disease. DBPA facilitates the bacteria's colonization of human tissue by adhering to glycosaminoglycan (GAG), a sulfated polysaccharide. Interestingly, DBPA sequence variation among different strains of Borrelia spirochetes is high, resulting in significant differences in their GAG affinities. However, the structural mechanisms contributing to these differences are unknown. We determined the solution structures of DBPAs from strain N40 of B. burgdorferi and strain PBr of Borrelia garinii, two DBPA variants whose GAG affinities deviate significantly from strain B31, the best characterized version of DBPA. Our structures revealed that significant differences exist between PBr DBPA and B31/N40 DBPAs. In particular, the C-terminus of PBr DBPA, unlike C-termini from B31 and N40 DBPAs, is positioned away from the GAG-binding pocket and the linker between helices one and two of PBr DBPA is highly structured and retracted from the GAG-binding pocket. The repositioning of the C-terminus allowed the formation of an extra GAG-binding epitope in PBr DBPA and the retracted linker gave GAG ligands more access to the GAG-binding epitopes than other DBPAs. Characterization of GAG ligands' interactions with wild-type (WT) PBr and mutants confirmed the importance of the second major GAG-binding epitope and established the fact that the two epitopes are independent of one another and the new epitope is as important to GAG binding as the traditional epitope.

  2. vls Antigenic Variation Systems of Lyme Disease Borrelia: Eluding Host Immunity through both Random, Segmental Gene Conversion and Framework Heterogeneity.

    PubMed

    Norris, Steven J

    2014-12-01

    Spirochetes that cause Lyme borreliosis (also called Lyme disease) possess the vls locus, encoding an elaborate antigenic variation system. This locus contains the expression site vlsE as well as a contiguous array of vls silent cassettes, which contain variations of the central cassette region of vlsE. The locus is present on one of the many linear plasmids in the organism, e.g. plasmid lp28-1 in the strain Borrelia burgdorferi B31. Changes in the sequence of vlsE occur continuously during mammalian infection and consist of random, segmental, unidirectional recombination events between the silent cassettes and the cassette region of vlsE. These gene conversion events do not occur during in vitro culture or the tick portion of the infection cycle of B. burgdorferi or the other related Borrelia species that cause Lyme disease. The mechanism of recombination is largely unknown, but requires the RuvAB Holliday junction branch migrase. Other features of the vls locus also appear to be required, including cis locations of vlsE and the silent cassettes and high G+C content and GC skew. The vls system is required for long-term survival of Lyme Borrelia in infected mammals and represents an important mechanism of immune evasion. In addition to sequence variation, immune selection also results in significant heterogeneity in the sequence of the surface lipoprotein VlsE. Despite antigenic variation, VlsE generates a robust antibody response, and both full-length VlsE and the C6 peptide (corresponding to invariant region 6) are widely used in immunodiagnostic tests for Lyme disease.

  3. Characterization of a DNA Adenine Methyltransferase Gene of Borrelia hermsii and Its Dispensability for Murine Infection and Persistence.

    PubMed

    James, Allison E; Rogovskyy, Artem S; Crowley, Michael A; Bankhead, Troy

    2016-01-01

    DNA methyltransferases have been implicated in the regulation of virulence genes in a number of pathogens. Relapsing fever Borrelia species harbor a conserved, putative DNA methyltransferase gene on their chromosome, while no such ortholog can be found in the annotated genome of the Lyme disease agent, Borrelia burgdorferi. In the relapsing fever species Borrelia hermsii, the locus bh0463A encodes this putative DNA adenine methyltransferase (dam). To verify the function of the BH0463A protein product as a Dam, the gene was cloned into a Dam-deficient strain of Escherichia coli. Restriction fragment analysis subsequently demonstrated that complementation of this E. coli mutant with bh0463A restored adenine methylation, verifying bh0463A as a Dam. The requirement of bh0463A for B. hermsii viability, infectivity, and persistence was then investigated by genetically disrupting the gene. The dam- mutant was capable of infecting immunocompetent mice, and the mean level of spirochetemia in immunocompetent mice was not significantly different from wild type B. hermsii. Collectively, the data indicate that dam is dispensable for B. hermsii viability, infectivity, and persistence. PMID:27195796

  4. Characterization of a DNA Adenine Methyltransferase Gene of Borrelia hermsii and Its Dispensability for Murine Infection and Persistence

    PubMed Central

    James, Allison E.; Rogovskyy, Artem S.; Crowley, Michael A.; Bankhead, Troy

    2016-01-01

    DNA methyltransferases have been implicated in the regulation of virulence genes in a number of pathogens. Relapsing fever Borrelia species harbor a conserved, putative DNA methyltransferase gene on their chromosome, while no such ortholog can be found in the annotated genome of the Lyme disease agent, Borrelia burgdorferi. In the relapsing fever species Borrelia hermsii, the locus bh0463A encodes this putative DNA adenine methyltransferase (dam). To verify the function of the BH0463A protein product as a Dam, the gene was cloned into a Dam-deficient strain of Escherichia coli. Restriction fragment analysis subsequently demonstrated that complementation of this E. coli mutant with bh0463A restored adenine methylation, verifying bh0463A as a Dam. The requirement of bh0463A for B. hermsii viability, infectivity, and persistence was then investigated by genetically disrupting the gene. The dam- mutant was capable of infecting immunocompetent mice, and the mean level of spirochetemia in immunocompetent mice was not significantly different from wild type B. hermsii. Collectively, the data indicate that dam is dispensable for B. hermsii viability, infectivity, and persistence. PMID:27195796

  5. Dengue fever (image)

    MedlinePlus

    Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

  6. Identification of host blood-meal sources and Borrelia in field-collected Ixodes ricinus ticks in north-western Poland.

    PubMed

    Wodecka, Beata; Skotarczak, Bogumila

    2016-01-01

    Forest animals play fundamental roles in the maintenance of Ixodes ricinus and Borrelia species in the forest biotope. To identify the forest vertebrate species that are host for I. ricinus and for the recognition of the reservoirs of Borrelia species, the blood-meal of 325 I. ricinus ticks collected at two forest sites in north-western Poland were analysed. Nested PCR was used to detect polymorphisms in a fragment of the mitochondrial 12S rRNA gene for the identification of the hosts species. The products were digested with the restriction enzymes, a combination that allows the identification of 60 vertebrate species, comprising 17 bird, 4 reptile and 39 mammalian species. Host DNA was detected in 244 (75%) I. ricinus individuals, with the species being detected and classified for 210 (86%) samples. The restriction patterns resulted in the identification of 14 vertebrate species, including 2 species of birds, lizard, badger, rabbit, deer; most of the samples contained DNA from wild boar (Sus scrofa), red fox (Vulpes vulpes), red deer (Cervus elaphus) and roe deer (Capreolus capreolus). Identification of Borrelia species was based on the flaB gene using nested PCR coupled to RFLP. This method allows the identification of all Borrelia species transmitted by I. ricinus in Europe, including B. miyamotoi and 3 genetic variants of B. garinii. In the studied isolates, 2 species belonging to B. burgdorferi sensu lato were identified--B. garinii and B. afzelii, and B. miyamotoi, which are related to relapsing fever borreliae. PMID:27007518

  7. Spirochete attachment ultrastructure: Implications for the origin and evolution of cilia.

    PubMed

    Wier, Andrew M; Sacchi, Luciano; Dolan, Michael F; Bandi, Claudio; Macallister, James; Margulis, Lynn

    2010-02-01

    The fine structure of spirochete attachments to the plasma membrane of anaerobic protists displays variations here interpreted as legacies of an evolutionary sequence analogous to that from free-living spirochetes to undulipodia (eukaryotic "flagella" and homologous structures). Attached spirochetes form a vestment, a wriggling fringe of motile cells at the edge of the plasma membrane of unidentified cellulolytic protist cells in the hypertrophied hindgut of the digestive system of Mastotermes darwiniensis, the large wood-feeding termite from northern Australia. From the membrane extend both undulipodia and a complex of comparably sized (10-12 microm x 0.2-0.3 microm) ectosymbiotic spirochetes that resembles unruly ciliated epithelium. In the intestines are helical (swimming) and round-body morphotypes. Round bodies (RBs) are slow or immotile spirochetes, propagules known to revert to typical swimming helices under culture conditions favorable for growth. The surfaces of both the spirochete gram-negative eubacteria and the parabasalid protists display distinctive attachment structures. The attached hypertrophied structures, some of which resemble ciliate kinetids, are found consistently at sites where the spirochete termini contact the protist plasma membranes. PMID:20203251

  8. Spirochete attachment ultrastructure: Implications for the origin and evolution of cilia.

    PubMed

    Wier, Andrew M; Sacchi, Luciano; Dolan, Michael F; Bandi, Claudio; Macallister, James; Margulis, Lynn

    2010-02-01

    The fine structure of spirochete attachments to the plasma membrane of anaerobic protists displays variations here interpreted as legacies of an evolutionary sequence analogous to that from free-living spirochetes to undulipodia (eukaryotic "flagella" and homologous structures). Attached spirochetes form a vestment, a wriggling fringe of motile cells at the edge of the plasma membrane of unidentified cellulolytic protist cells in the hypertrophied hindgut of the digestive system of Mastotermes darwiniensis, the large wood-feeding termite from northern Australia. From the membrane extend both undulipodia and a complex of comparably sized (10-12 microm x 0.2-0.3 microm) ectosymbiotic spirochetes that resembles unruly ciliated epithelium. In the intestines are helical (swimming) and round-body morphotypes. Round bodies (RBs) are slow or immotile spirochetes, propagules known to revert to typical swimming helices under culture conditions favorable for growth. The surfaces of both the spirochete gram-negative eubacteria and the parabasalid protists display distinctive attachment structures. The attached hypertrophied structures, some of which resemble ciliate kinetids, are found consistently at sites where the spirochete termini contact the protist plasma membranes.

  9. Orchid Fever

    ERIC Educational Resources Information Center

    Oliver, Phillip

    2004-01-01

    Exotic, captivating, and seductive, orchids have long fascinated plant lovers. They first attracted the attention of Westerners in the 17th century, when explorers brought back samples from South America and Asia. By the mid-1800s, orchid collecting had reached a fever pitch, not unlike that of the Dutch tulip craze of the 1630s, with rich (and…

  10. Scarlet fever.

    PubMed

    2016-04-27

    Essential facts Scarlet fever is characterised by a rash that usually accompanies a sore throat and flushed cheeks. It is mainly a childhood illness. While this contagious disease rarely poses a danger to life today, outbreaks in the past led to many deaths.

  11. Dengue Fever

    Technology Transfer Automated Retrieval System (TEKTRAN)

    “Dengue Fever” will be included in “Health Information for International Travel, 2007-2008” which will be published by the U.S. Centers for Disease Control and Prevention. Dengue and dengue hemorrhagic fever are viral diseases transmitted by Aedes mosquitoes. The disease is found in tropical and s...

  12. Spirosymplokos deltaeiberi nov. gen., nov. sp.: variable-diameter composite spirochete from microbial mats

    NASA Technical Reports Server (NTRS)

    Guerrero, R.; Ashen, J.; Sole, M.; Margulis, L.

    1993-01-01

    Large (up to 100 micrometers long), loosely coiled, free-living spirochetes with variable diameters (from 0.4 to 3 micrometers in the same cell) were seen at least 40 times between August 1990 and January 1993. These spirochetes were observed in mud water and enrichment media from highly specific habitats in intertidal evaporite flats at three disjunct localities, one in Spain and two in Mexico. All three are sites of commercial saltworks. Associated with Microcoleus chthonoplastes the large spirochetes from Spain display phototaxis and a composite organization. Shorter and smaller-diameter spirochetes are seen inside both healthy and spent periplasm of larger ones. Small spirochetes attached to large ones have been observed live. From two to twelve spirochete protoplasmic cylinders were seen inside a single common outer membrane. A distinctive granulated cytoplasm in which the granules are of similar diameter (20-32 nanometers) to that of the flagella (26 nanometers) was present. Granule diameters were measured in thin section and in negatively-stained whole-mount preparations. Based on their ultrastructure, large size, variable diameter, number of flagella (3 to 6), and phototactic behavior these unique spirochetes are formally named Spirosymplokos deltaeiberi. Under anoxic (or low oxygen) conditions they formed blooms in mixed culture in media selective for spirochetes. Cellobiose was the major carbon source in 80% seawater, the antibiotic rifampicin was added, mat from the original field site was present and tubes were incubated in the light at from 18-31 degrees C. Within 1-2 weeks populations of the large spirochete developed at 25 degrees C but they could not be transferred to fresh medium.

  13. Oligoarthritis caused by Borrelia bavariensis, Austria, 2014.

    PubMed

    Markowicz, Mateusz; Ladstatter, Stefan; Schotta, Anna M; Reiter, Michael; Pomberger, Gerhard; Stanek, Gerold

    2015-06-01

    A case of Lyme oligoarthritis occurred in an 11-year-old boy in Vienna, Austria. DNA of Borrelia bavariensis was detected by PCR in 2 aspirates obtained from different joints. Complete recovery was achieved after a 4-week course with amoxicillin. Lyme arthritis must be considered in patients from Europe who have persisting joint effusions.

  14. Oligoarthritis Caused by Borrelia bavariensis, Austria, 2014

    PubMed Central

    Ladstätter, Stefan; Schötta, Anna M.; Reiter, Michael; Pomberger, Gerhard; Stanek, Gerold

    2015-01-01

    A case of Lyme oligoarthritis occurred in an 11-year-old boy in Vienna, Austria. DNA of Borrelia bavariensis was detected by PCR in 2 aspirates obtained from different joints. Complete recovery was achieved after a 4-week course with amoxicillin. Lyme arthritis must be considered in patients from Europe who have persisting joint effusions. PMID:25992945

  15. Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: evidence for a conformational protective epitope in OspC.

    PubMed

    Gilmore, R D; Kappel, K J; Dolan, M C; Burkot, T R; Johnson, B J

    1996-06-01

    Outbred mice were immunized with the soluble fraction of a crude Escherichia coli lysate containing either recombinant outer surface protein C (OspC or P39 of Borrelia burgdorferi B31 (low passage). Following seroconversion, the mice were challenged with an infectious dose of B. burgdorferi B31 via the natural transmission mode of tick bite. Three mice immunized with P39 were not protected; however, all 12 of the recombinant OspC-immunized mice were protected from infection as assayed by culture and serology. Although OspC has been shown to be a protective immunogen against challenge with in vitro-cultured borrelia administered by needle, this study is the first to demonstrate OspC effectiveness against tick-borne spirochetes. Following feeding, all ticks still harbored B. burgdorferi, suggesting that the mechanism of protection is not linked to destruction of the infectious spirochete within the tick. In a separate experiment, groups of four mice were immunized with protein fractions from B. burgdorferi B31 purified by preparative gel electrophoresis in an attempt to identify potential protective antigens. Many of these mice developed high-titer-antibody responses against OspC, but curiously the mice were susceptible to B. burgdorferi infection via tick bite. These results suggest that the protective epitope(s) on OspC is heat sensitive/conformational, a finding which has implications in vaccine development.

  16. An efficient method for enumerating oral spirochetes using flow cytometry.

    PubMed

    Orth, Rebecca; O'Brien-Simpson, Neil; Dashper, Stuart; Walsh, Katrina; Reynolds, Eric

    2010-02-01

    Spirochetes, such as Treponema denticola, are thin walled, helical, motile bacteria. They are notoriously difficult to enumerate due to their thinness and the difficulties associated with culturing them. Here we have developed a modified oral bacterial growth medium (OBGM) that significantly improves the cultivation of T. denticola compared with a previously published growth medium. Three methods for the enumeration of T. denticola, semi-solid growth medium colony-forming unit (CFU) counts, DNA analysis and flow cytometry, are described and compared. Enumeration of T. denticola using the semi-solid agar method resulted in a positive linear relationship with absorbance of the culture (R(2)=0.9423). However, the semi-solid agar method was found to consistently underestimate (by 50 fold) the T. denticola cell density compared to previously published data. DNA analysis of T. denticola cultures reliably and consistently resulted in a positive linear relationship with absorbance (R(2)=0.9360), giving a calculated cell density of 6.9 x 10(8)cells/mL at an absorbance of 0.2 at 650 nm. Flow cytometry was also found to result in a positive linear relationship with absorbance (R(2)=0.9874), giving a calculated cell density of 6.6 x 10(8)cells/mL at an absorbance of 0.2 at 650 nm. In comparing all of these enumeration methods, the flow cytometry method was found to have distinct advantages, as it is accurate, rapid, and could distinguish between live and dead bacteria. Thus flow cytometry is a recommended means for the rapid and reliable enumeration of viable spirochetes from culture.

  17. The salt-sensitive structure and zinc inhibition of Borrelia burgdorferi protease BbHtrA.

    PubMed

    Russell, Theresa M; Tang, Xiaoling; Goldstein, Jason M; Bagarozzi, Dennis; Johnson, Barbara J B

    2016-02-01

    HtrA serine proteases are highly conserved and essential ATP-independent proteases with chaperone activity. Bacteria express a variable number of HtrA homologues that contribute to the virulence and pathogenicity of bacterial pathogens. Lyme disease spirochetes possess a single HtrA protease homologue, Borrelia burgdorferi HtrA (BbHtrA). Previous studies established that, like the human orthologue HtrA1, BbHtrA is proteolytically active against numerous extracellular proteins in vitro. In this study, we utilized size exclusion chromatography and blue native polyacrylamide gel electrophoresis (BN-PAGE) to demonstrate BbHtrA oligomeric structures that were substrate independent and salt sensitive. Examination of the influence of transition metals on the activity of BbHtrA revealed that this protease is inhibited by Zn(2+) > Cu(2+) > Mn(2+). Extending this analysis to two other HtrA proteases, E. coli DegP and HtrA1, revealed that all three HtrA proteases were reversibly inhibited by ZnCl2 at all micro molar concentrations examined. Commercial inhibitors for HtrA proteases are not available and physiologic HtrA inhibitors are unknown. Our observation of conserved zinc inhibition of HtrA proteases will facilitate structural and functional studies of additional members of this important class of proteases. PMID:26480895

  18. Borrelia burgdorferi has minimal impact on the Lyme disease reservoir host Peromyscus leucopus.

    PubMed

    Schwanz, Lisa E; Voordouw, Maarten J; Brisson, Dustin; Ostfeld, Richard S

    2011-02-01

    The epidemiology of vector-borne zoonotic diseases is determined by encounter rates between vectors and hosts. Alterations to the behavior of reservoir hosts caused by the infectious agent have the potential to dramatically alter disease transmission and human risk. We examined the effect of Borrelia burgdorferi, the etiological agent of Lyme disease, on one of its most important reservoir hosts, the white-footed mouse, Peromyscus leucopus. We mimic natural infections in mice using the vector (Black-legged ticks, Ixodes scapularis) and examine the immunological and behavioral responses of mouse hosts. Despite producing antibodies against B. burgdorferi, infected mice did not have elevated white blood cells compared with uninfected mice. In addition, infected and uninfected mice did not differ in their wheel-running activity. Our results suggest that infection with the spirochete B. burgdorferi has little impact on the field activity of white-footed mice. Lyme disease transmission appears to be uncomplicated by pathogen-altered behavior of this reservoir host. PMID:20569016

  19. Microarray-Based Comparative Genomic and Transcriptome Analysis of Borrelia burgdorferi

    PubMed Central

    Iyer, Radha; Schwartz, Ira

    2016-01-01

    Borrelia burgdorferi, the spirochetal agent of Lyme disease, is maintained in nature in a cycle involving a tick vector and a mammalian host. Adaptation to the diverse conditions of temperature, pH, oxygen tension and nutrient availability in these two environments requires the precise orchestration of gene expression. Over 25 microarray analyses relating to B. burgdorferi genomics and transcriptomics have been published. The majority of these studies has explored the global transcriptome under a variety of conditions and has contributed substantially to the current understanding of B. burgdorferi transcriptional regulation. In this review, we present a summary of these studies with particular focus on those that helped define the roles of transcriptional regulators in modulating gene expression in the tick and mammalian milieus. By performing comparative analysis of results derived from the published microarray expression profiling studies, we identified composite gene lists comprising differentially expressed genes in these two environments. Further, we explored the overlap between the regulatory circuits that function during the tick and mammalian phases of the enzootic cycle. Taken together, the data indicate that there is interplay among the distinct signaling pathways that function in feeding ticks and during adaptation to growth in the mammal. PMID:27600075

  20. Borrelia burgdorferi needs chemotaxis to establish infection in mammals and to accomplish its enzootic cycle.

    PubMed

    Sze, Ching Wooen; Zhang, Kai; Kariu, Toru; Pal, Utpal; Li, Chunhao

    2012-07-01

    Borrelia burgdorferi, the causative agent of Lyme disease, can be recovered from different organs of infected animals and patients, indicating that the spirochete is very invasive. Motility and chemotaxis contribute to the invasiveness of B. burgdorferi and play important roles in the process of the disease. Recent reports have shown that motility is required for establishing infection in mammals. However, the role of chemotaxis in virulence remains elusive. Our previous studies showed that cheA₂, a gene encoding a histidine kinase, is essential for the chemotaxis of B. burgdorferi. In this report, the cheA₂ gene was inactivated in a low-passage-number virulent strain of B. burgdorferi. In vitro analyses (microscopic observations, computer-based bacterial tracking analysis, swarm plate assays, and capillary tube assays) showed that the cheA₂ mutant failed to reverse and constantly ran in one direction; the mutant was nonchemotactic to attractants. Mouse needle infection studies showed that the cheA₂ mutant failed to infect either immunocompetent or immunodeficient mice and was quickly eliminated from the initial inoculation sites. Tick-mouse infection studies revealed that although the mutant was able to survive in ticks, it failed to establish a new infection in mice via tick bites. The altered phenotypes were completely restored when the mutant was complemented. Collectively, these data demonstrate that B. burgdorferi needs chemotaxis to establish mammalian infection and to accomplish its natural enzootic cycle.

  1. Borrelia burgdorferi erp genes are expressed at different levels within tissues of chronically infected mammalian hosts.

    PubMed

    Miller, Jennifer C; Stevenson, Brian

    2006-05-01

    The spirochete Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans and other vertebrate hosts through the bites of ixodid ticks. B. burgdorferi Erp (OspE-F related lipoprotein) family members are encoded on members of the 32 kb circular plasmid-like prophage family (cp32s). Many Erp proteins serve as receptors for the complement inhibitory factor H molecules of numerous vertebrate hosts, providing one mechanism by which the bacteria potentially evade the innate immune system. Indirect immunofluorescence analyses (IFA) have demonstrated that Erp expression is temporally regulated throughout the mammal-tick infectious cycle, indicating that Erp proteins perform an important role (or even roles) during mammalian infection. However, it was not previously known whether Erp proteins are continually produced by B. burgdorferi throughout the course of mammalian infection. To address this issue, quantitative RT-PCR (q-RT-PCR) was utilized to assess erp transcription levels by bacteria within numerous different tissues of both mice and non-human primates (NHPs) chronically infected with B. burgdorferi. Q-RT-PCR results obtained using both animal models indicated that while the majority of erp genes were detectably transcribed during chronic infection, differences in expression levels were noted. These data strongly suggest that Erp proteins contribute to B. burgdorferi persistence within chronically infected host tissues, perhaps by protecting the bacteria from complement-mediated killing. PMID:16530008

  2. Borrelia burgdorferi BmpA Is a Laminin-Binding Protein▿

    PubMed Central

    Verma, Ashutosh; Brissette, Catherine A.; Bowman, Amy; Stevenson, Brian

    2009-01-01

    The Borrelia burgdorferi BmpA outer surface protein plays a significant role in mammalian infection by the Lyme disease spirochete and is an important antigen for the serodiagnosis of human infection. B. burgdorferi adheres to host extracellular matrix components, including laminin. The results of our studies indicate that BmpA and its three paralogous proteins, BmpB, BmpC, and BmpD, all bind to mammalian laminin. BmpA did not bind mammalian type I or type IV collagens or fibronectin. BmpA-directed antibodies significantly inhibited the adherence of live B. burgdorferi to laminin. The laminin-binding domain of BmpA was mapped to the carboxy-terminal 80 amino acids. Solubilized collagen inhibited BmpA-laminin binding, suggesting interactions through the collagen-binding domains of laminin. These results, together with previous data, indicate that BmpA and its paralogs are targets for the development of preventative and curative therapies for Lyme disease. PMID:19703983

  3. Substrate prediction of Ixodes ricinus salivary lipocalins differentially expressed during Borrelia afzelii infection

    PubMed Central

    Valdés, James J.; Cabezas-Cruz, Alejandro; Sima, Radek; Butterill, Philip T.; Růžek, Daniel; Nuttall, Patricia A.

    2016-01-01

    Evolution has provided ticks with an arsenal of bioactive saliva molecules that counteract host defense mechanisms. This salivary pharmacopoeia enables blood-feeding while enabling pathogen transmission. High-throughput sequencing of tick salivary glands has thus become a major focus, revealing large expansion within protein encoding gene families. Among these are lipocalins, ubiquitous barrel-shaped proteins that sequester small, typically hydrophobic molecules. This study was initiated by mining the Ixodes ricinus salivary gland transcriptome for specific, uncharacterized lipocalins: three were identified. Differential expression of these I. ricinus lipocalins during feeding at distinct developmental stages and in response to Borrelia afzelii infection suggests a role in transmission of this Lyme disease spirochete. A phylogenetic analysis using 803 sequences places the three I. ricinus lipocalins with tick lipocalins that sequester monoamines, leukotrienes and fatty acids. Both structural analysis and biophysical simulations generated robust predictions showing these I. ricinus lipocalins have the potential to bind monoamines similar to other tick species previously reported. The multidisciplinary approach employed in this study characterized unique lipocalins that play a role in tick blood-feeding and transmission of the most important tick-borne pathogen in North America and Eurasia. PMID:27584086

  4. Borrelia burgdorferi BBA52 is a potential target for transmission blocking Lyme disease vaccine.

    PubMed

    Kumar, Manish; Kaur, Simarjot; Kariu, Toru; Yang, Xiuli; Bossis, Ioannis; Anderson, John F; Pal, Utpal

    2011-11-01

    The surface-exposed antigens of Borrelia burgdorferi represent important targets for induction of protective host immune responses. BBA52 is preferentially expressed by B. burgdorferi in the feeding tick, and a targeted deletion of bba52 interferes with vector-host transitions in vivo. In this study, we demonstrate that BBA52 is an outer membrane surface-exposed protein and that disulfide bridges take part in the homo-oligomeric assembly of native protein. BBA52 antibodies lack detectable borreliacidal activities in vitro. However, active immunization studies demonstrated that BBA52 vaccinated mice were significantly less susceptible to subsequent tick-borne challenge infection. Similarly, passive transfer of BBA52 antibodies in ticks completely blocked B. burgdorferi transmission from feeding ticks to naïve mice. Taken together, these studies highlight the role of BBA52 in spirochete dissemination from ticks to mice and demonstrate the potential of BBA52 antibody-mediated strategy to complement the ongoing efforts to develop vaccines for blocking the transmission of B. burgdorferi.

  5. Borrelia burgdorferi has minimal impact on the Lyme disease reservoir host Peromyscus leucopus.

    PubMed

    Schwanz, Lisa E; Voordouw, Maarten J; Brisson, Dustin; Ostfeld, Richard S

    2011-02-01

    The epidemiology of vector-borne zoonotic diseases is determined by encounter rates between vectors and hosts. Alterations to the behavior of reservoir hosts caused by the infectious agent have the potential to dramatically alter disease transmission and human risk. We examined the effect of Borrelia burgdorferi, the etiological agent of Lyme disease, on one of its most important reservoir hosts, the white-footed mouse, Peromyscus leucopus. We mimic natural infections in mice using the vector (Black-legged ticks, Ixodes scapularis) and examine the immunological and behavioral responses of mouse hosts. Despite producing antibodies against B. burgdorferi, infected mice did not have elevated white blood cells compared with uninfected mice. In addition, infected and uninfected mice did not differ in their wheel-running activity. Our results suggest that infection with the spirochete B. burgdorferi has little impact on the field activity of white-footed mice. Lyme disease transmission appears to be uncomplicated by pathogen-altered behavior of this reservoir host.

  6. GENETIC AND IMMUNOLOGICAL EVIDENCES OF BORRELIA BURGDORFERI IN DOG IN THAILAND.

    PubMed

    Sthitmatee, Nattawooti; Jinawan, Wanna; Jaisan, Nawaporn; Tangjitjaroen, Weerapongse; Chailangkarn, Sasisophin; Sodarat, Chollada; Ekgatat, Monaya; Padungtod, Pawin

    2016-01-01

    Lyme disease is a tick-borne zoonotic disease caused by spirochete Borrelia burgdorferi. It is transmitted from animals to humans by the bite of infected ticks of the genus Ixodes. Although Lyme disease has been reported in China and Japan, the disease has never been reported in Thailand. Blood samples and ticks were collected from 402 dogs from 7 and 3 animal clinics in Chiang Mai and Phuket Provinces, Thailand, respectively. Blood samples were tested for antibodies against B. burgdorferi, Anaplasma spp, Ehrlichia spp and Dirofilaria immitis using a commercial kit, and positive blood samples were subjected to nested PCR assay for B. burgdorferi fla, ospA and ospC, amplicons of which also were sequenced. Only one dog (from Chiang Mai) was positive for B. burgdorferi, with 97% to 100% genetic identity, depending on the sequences used for comparison, with strains from United State of America. All 376 ticks collected were Rhipicephalus sanguineus, but no tick was found on the infected dog. Further investigations of the infection source and vector are needed to understand potential risks of Lyme disease to dogs and humans in Thailand.

  7. Microarray-Based Comparative Genomic and Transcriptome Analysis of Borrelia burgdorferi.

    PubMed

    Iyer, Radha; Schwartz, Ira

    2016-01-01

    Borrelia burgdorferi, the spirochetal agent of Lyme disease, is maintained in nature in a cycle involving a tick vector and a mammalian host. Adaptation to the diverse conditions of temperature, pH, oxygen tension and nutrient availability in these two environments requires the precise orchestration of gene expression. Over 25 microarray analyses relating to B. burgdorferi genomics and transcriptomics have been published. The majority of these studies has explored the global transcriptome under a variety of conditions and has contributed substantially to the current understanding of B. burgdorferi transcriptional regulation. In this review, we present a summary of these studies with particular focus on those that helped define the roles of transcriptional regulators in modulating gene expression in the tick and mammalian milieus. By performing comparative analysis of results derived from the published microarray expression profiling studies, we identified composite gene lists comprising differentially expressed genes in these two environments. Further, we explored the overlap between the regulatory circuits that function during the tick and mammalian phases of the enzootic cycle. Taken together, the data indicate that there is interplay among the distinct signaling pathways that function in feeding ticks and during adaptation to growth in the mammal. PMID:27600075

  8. Substrate prediction of Ixodes ricinus salivary lipocalins differentially expressed during Borrelia afzelii infection.

    PubMed

    Valdés, James J; Cabezas-Cruz, Alejandro; Sima, Radek; Butterill, Philip T; Růžek, Daniel; Nuttall, Patricia A

    2016-01-01

    Evolution has provided ticks with an arsenal of bioactive saliva molecules that counteract host defense mechanisms. This salivary pharmacopoeia enables blood-feeding while enabling pathogen transmission. High-throughput sequencing of tick salivary glands has thus become a major focus, revealing large expansion within protein encoding gene families. Among these are lipocalins, ubiquitous barrel-shaped proteins that sequester small, typically hydrophobic molecules. This study was initiated by mining the Ixodes ricinus salivary gland transcriptome for specific, uncharacterized lipocalins: three were identified. Differential expression of these I. ricinus lipocalins during feeding at distinct developmental stages and in response to Borrelia afzelii infection suggests a role in transmission of this Lyme disease spirochete. A phylogenetic analysis using 803 sequences places the three I. ricinus lipocalins with tick lipocalins that sequester monoamines, leukotrienes and fatty acids. Both structural analysis and biophysical simulations generated robust predictions showing these I. ricinus lipocalins have the potential to bind monoamines similar to other tick species previously reported. The multidisciplinary approach employed in this study characterized unique lipocalins that play a role in tick blood-feeding and transmission of the most important tick-borne pathogen in North America and Eurasia. PMID:27584086

  9. Boutonneuse fever.

    PubMed Central

    Moraga, F A; Martinez-Roig, A; Alonso, J L; Boronat, M; Domingo, F

    1982-01-01

    Sixty children, aged between 2 and 10 years, had boutonneuse fever during the summer months of 1979 and 1980. They presented with fever and a generalised maculopapular rash. The tàche noire could be seen at the site of the tick bite in 38 (63%) of them. The antibody response, assayed nonspecifically, by the Weil-Felix reaction was positive in 52. A singe titre of more than 1:80 or a 4-fold increase between two paired specimens separated by a 7-day interval was considered diagnostic. Maximum titres were reached at the end of the second week of convalescence in 81% of patients. Treatment with oral oxytetracycline was effective in all cases. Images Fig. 1 Fig. 2 Fig. 3 PMID:7065712

  10. Zika fever.

    PubMed

    Martínez de Salazar, Pablo; Suy, Anna; Sánchez-Montalvá, Adrián; Rodó, Carlota; Salvador, Fernando; Molina, Israel

    2016-04-01

    Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between Zika infection and complications, such as microencephaly or Guillem-Barré syndrome. PMID:26993436

  11. Zika fever.

    PubMed

    Martínez de Salazar, Pablo; Suy, Anna; Sánchez-Montalvá, Adrián; Rodó, Carlota; Salvador, Fernando; Molina, Israel

    2016-04-01

    Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between Zika infection and complications, such as microencephaly or Guillem-Barré syndrome.

  12. Experimental Lyme disease in rabbits: spirochetes found in erythema migrans and blood.

    PubMed Central

    Kornblatt, A N; Steere, A C; Brownstein, D G

    1984-01-01

    In attempts to produce experimental Lyme disease, 33 rabbits were inoculated with Lyme spirochetes by tick feeding or from tick organ homogenates or cultures. Two rabbits developed erythema chronicum migrans at the site of inoculation, in one instance 2 days after injection of a tick organ homogenate and in the other instance, 17 days after feeding of infected Ixodes dammini ticks. Spirochetes were seen in skin biopsy specimens of the second lesion with Warthin-Starry and immunoperoxidase stains. Spirochetes were also recovered from blood cultures of two additional rabbits 2 weeks post-inoculation. These findings are characteristic of early Lyme disease in humans and give additional support for the spirochetal etiology of Lyme disease. Images PMID:6480108

  13. Interactions of phagocytes with the Lyme disease spirochete: role of the Fc receptor

    SciTech Connect

    Benach, J.L.; Fleit, H.B.; Habicht, G.S.; Coleman, J.L.; Bosler, E.M.; Lane, B.P.

    1984-10-01

    The phagocytic capacity of murine and human mononuclear and polymorphonuclear phagocytes (including peripheral blood monocytes and neutrophils), rabbit and murine peritoneal exudate cells, and the murine macrophage cell line P388D1 against the Lyme disease spirochete was studied. All of these cells were capable of phagocytosing the spirochete; phagocytosis was measured by the uptake of radiolabeled spirochetes, the appearance of immunofluorescent bodies in phagocytic cells, and electron microscopy. Both opsonized and nonopsonized organisms were phagocytosed. The uptake of opsonized organisms by neutrophils was blocked by a monoclonal antibody specific for the Fc receptor and by immune complexes; these findings suggested that most phagocytosis is mediated by the Fc receptor. Similarly, the uptake of opsonized organisms by human monocytes was inhibited by human monomeric IgG1 and by immune complexes. These results illustrate the role of immune phagocytosis of spirochetes in host defense against Lyme disease.

  14. Typhoid fever.

    PubMed

    Wain, John; Hendriksen, Rene S; Mikoleit, Matthew L; Keddy, Karen H; Ochiai, R Leon

    2015-03-21

    Control of typhoid fever relies on clinical information, diagnosis, and an understanding for the epidemiology of the disease. Despite the breadth of work done so far, much is not known about the biology of this human-adapted bacterial pathogen and the complexity of the disease in endemic areas, especially those in Africa. The main barriers to control are vaccines that are not immunogenic in very young children and the development of multidrug resistance, which threatens efficacy of antimicrobial chemotherapy. Clinicians, microbiologists, and epidemiologists worldwide need to be familiar with shifting trends in enteric fever. This knowledge is crucial, both to control the disease and to manage cases. Additionally, salmonella serovars that cause human infection can change over time and location. In areas of Asia, multidrug-resistant Salmonella enterica serovar Typhi (S Typhi) has been the main cause of enteric fever, but now S Typhi is being displaced by infections with drug-resistant S enterica serovar Paratyphi A. New conjugate vaccines are imminent and new treatments have been promised, but the engagement of local medical and public health institutions in endemic areas is needed to allow surveillance and to implement control measures.

  15. Characterization of an anti-Borrelia burgdorferi OspA conformational epitope by limited proteolysis of monoclonal antibody-bound antigen and mass spectrometric peptide mapping.

    PubMed Central

    Legros, V.; Jolivet-Reynaud, C.; Battail-Poirot, N.; Saint-Pierre, C.; Forest, E.

    2000-01-01

    Lyme borreliosis is a multisystem disorder caused by the spirochete Borrelia burgdorferi that is transmitted to humans by the tick Ixodes dammini. The immune response against the 31 kDa OspA, which is one of the most abundant B. burgdorferi proteins, appears to be critical in preventing infection and tissue inflammation. Detailed knowledge of the immunological and molecular characteristics of the OspA protein is important for the development of reliable diagnostic assays. In this study, we characterized a new conformational epitope present within the middle part of B. burgdorferi OspA. Our approach used enzymatic proteolyses of the immune complex followed by mass spectrometric identification of the peptides bound to the antibody. It appears to be one of the first reports on the characterization of a discontinuous epitope using mass spectrometry. PMID:10850810

  16. Biochemical and biophysical characterization of the major outer surface protein, OSP-A from North American and European isolates of Borrelia burgdorferi

    SciTech Connect

    McGrath, B.C.; Dunn, J.J.; France, L.L.; Jaing, W.; Polin, D.; Gorgone, G.; Luft, B.; Dykhuizen, D.

    1995-12-31

    Lyme borreliosis, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in North America and Western Europe. As the major delayed immune response in humans, a better understanding of the major outer surface lipoproteins OspA and OspB are of much interest. These proteins have been shown to exhibit three distinct phylogenetic genotypes based on their DNA sequences. This paper describes the cloning of genomic DNA for each variant and amplification of PCR. DNA sequence data was used to derive computer driven phylogenetic analysis and deduced amino acid sequences. Overproduction of variant OspAs was carried out in E. coli using a T7-based expression system. Circular dichroism and fluorescence studies was carried out on the recombinant B31 PspA yielding evidence supporting a B31 protein containing 11% alpha-helix, 34% antiparallel beta-sheet, 12% parallel beta sheet.

  17. Selective association of outer surface lipoproteins with the lipid rafts of Borrelia burgdorferi.

    PubMed

    Toledo, Alvaro; Crowley, Jameson T; Coleman, James L; LaRocca, Timothy J; Chiantia, Salvatore; London, Erwin; Benach, Jorge L

    2014-03-11

    Borrelia burgdorferi contains unique cholesterol-glycolipid-rich lipid rafts that are associated with lipoproteins. These complexes suggest the existence of macromolecular structures that have not been reported for prokaryotes. Outer surface lipoproteins OspA, OspB, and OspC were studied for their participation in the formation of lipid rafts. Single-gene deletion mutants with deletions of ospA, ospB, and ospC and a spontaneous gene mutant, strain B313, which does not express OspA and OspB, were used to establish their structural roles in the lipid rafts. All mutant strains used in this study produced detergent-resistant membranes, a common characteristic of lipid rafts, and had similar lipid and protein slot blot profiles. Lipoproteins OspA and OspB but not OspC were shown to be associated with lipid rafts by transmission electron microscopy. When the ability to form lipid rafts in live B. burgdorferi spirochetes was measured by fluorescence resonance energy transfer (FRET), strain B313 showed a statistically significant lower level of segregation into ordered and disordered membrane domains than did the wild-type and the other single-deletion mutants. The transformation of a B313 strain with a shuttle plasmid containing ospA restored the phenotype shared by the wild type and the single-deletion mutants, demonstrating that OspA and OspB have redundant functions. In contrast, a transformed B313 overexpressing OspC neither rescued the FRET nor colocalized with the lipid rafts. Because these lipoproteins are expressed at different stages of the life cycle of B. burgdorferi, their selective association is likely to have an important role in the structure of prokaryotic lipid rafts and in the organism's adaptation to changing environments. IMPORTANCE Lipid rafts are cholesterol-rich clusters within the membranes of cells. Lipid rafts contain proteins that have functions in sensing the cell environment and transmitting signals. Although selective proteins are present in

  18. Virulence of recurrent infestations with Borrelia-infected ticks in a Borrelia-amplifying bird

    NASA Astrophysics Data System (ADS)

    Heylen, Dieter J. A.; Müller, Wendt; Vermeulen, Anke; Sprong, Hein; Matthysen, Erik

    2015-11-01

    Lyme disease cases caused by Borrelia burgdorferi s.l. bacteria is increasing steadily in Europe, in part due to the expansion of the vector, Ixodes ricinus. Wild reservoir hosts are typically recurrently infested. Understanding the impact of these cumulative parasite exposures on the host’s health is, therefore, central to predict the distribution of tick populations and their pathogens. Here, we have experimentally investigated the symptoms of disease caused by recurrent infestations in a common songbird (Parus major). Birds were exposed three times in succession to ticks collected in a Borrelia endemic area. Health and immune measures were analyzed in order to investigate changes in response to tick infestation and Borrelia infection rate. Nitric oxide levels increased with the Borrelia infection rate, but this effect was increasingly counteracted by mounting tick infestation rates. Tick infestations equally reduced haematocrit during each cycle. But birds overcompensated in their response to tick feeding, having higher haematocrit values during tick-free periods depending on the number of ticks they had been previously exposed to. Body condition showed a similar overshooting response in function of the severity of the Borrelia infection. The observed overcompensation increases the bird’s energetic needs, which may result in an increase in transmission events.

  19. Virulence of recurrent infestations with Borrelia-infected ticks in a Borrelia-amplifying bird.

    PubMed

    Heylen, Dieter J A; Müller, Wendt; Vermeulen, Anke; Sprong, Hein; Matthysen, Erik

    2015-01-01

    Lyme disease cases caused by Borrelia burgdorferi s.l. bacteria is increasing steadily in Europe, in part due to the expansion of the vector, Ixodes ricinus. Wild reservoir hosts are typically recurrently infested. Understanding the impact of these cumulative parasite exposures on the host's health is, therefore, central to predict the distribution of tick populations and their pathogens. Here, we have experimentally investigated the symptoms of disease caused by recurrent infestations in a common songbird (Parus major). Birds were exposed three times in succession to ticks collected in a Borrelia endemic area. Health and immune measures were analyzed in order to investigate changes in response to tick infestation and Borrelia infection rate. Nitric oxide levels increased with the Borrelia infection rate, but this effect was increasingly counteracted by mounting tick infestation rates. Tick infestations equally reduced haematocrit during each cycle. But birds overcompensated in their response to tick feeding, having higher haematocrit values during tick-free periods depending on the number of ticks they had been previously exposed to. Body condition showed a similar overshooting response in function of the severity of the Borrelia infection. The observed overcompensation increases the bird's energetic needs, which may result in an increase in transmission events. PMID:26553505

  20. Virulence of recurrent infestations with Borrelia-infected ticks in a Borrelia-amplifying bird

    PubMed Central

    Heylen, Dieter J. A.; Müller, Wendt; Vermeulen, Anke; Sprong, Hein; Matthysen, Erik

    2015-01-01

    Lyme disease cases caused by Borrelia burgdorferi s.l. bacteria is increasing steadily in Europe, in part due to the expansion of the vector, Ixodes ricinus. Wild reservoir hosts are typically recurrently infested. Understanding the impact of these cumulative parasite exposures on the host’s health is, therefore, central to predict the distribution of tick populations and their pathogens. Here, we have experimentally investigated the symptoms of disease caused by recurrent infestations in a common songbird (Parus major). Birds were exposed three times in succession to ticks collected in a Borrelia endemic area. Health and immune measures were analyzed in order to investigate changes in response to tick infestation and Borrelia infection rate. Nitric oxide levels increased with the Borrelia infection rate, but this effect was increasingly counteracted by mounting tick infestation rates. Tick infestations equally reduced haematocrit during each cycle. But birds overcompensated in their response to tick feeding, having higher haematocrit values during tick-free periods depending on the number of ticks they had been previously exposed to. Body condition showed a similar overshooting response in function of the severity of the Borrelia infection. The observed overcompensation increases the bird’s energetic needs, which may result in an increase in transmission events. PMID:26553505

  1. Cosmopolitan distribution of the large composite microbial mat spirochete, Spirosymplokos deltaeiberi

    NASA Technical Reports Server (NTRS)

    Margulis, L.; Navarrete, A.; Sole, M.

    1998-01-01

    Inocula from organic-rich black muds immediately underlying intertidal laminated microbial mats dominated by Microcoleus chthonoplastes yielded large, variable diameter spirochetes. These unusual spirochetes, previously reported only from the Alfacs Peninsula at the delta of the Ebro river in northeast Spain, contain striking arrays of cytoplasmic granules packed into their protoplasmic cylinders. On several occasions, both in summer and winter, the huge spirochetes were recognized in samples from mats growing in the Sippewissett salt marsh at Woods Hole Massachusetts. They were also seen in similar samples from microbial mats at North Pond, Laguna Figueroa, Baja California Norte, Mexico. The identity of these spirochetes was confirmed by electron microscopy: number and disposition of flagella, composite structure, measurements of their distinctive cytoplasmic granules. The granules, larger, more conspicuous and present in addition to ribosomes, are hypothesized to contain ATPases. As culture conditions worsen, these spirochetes retract into membrane-bounded round bodies in which they form refractile inclusions. From morphology and behavior we conclude the North American spirochetes from both Atlantic and Pacific intertidal microbial mats are indistinguishable from those at the delta of the Ebro river. We conclude a cosmopolitan distribution for Spirosymplokos deltaeiberi.

  2. Short report: mode of action of protective immunity to Lyme disease spirochetes.

    PubMed

    Shih, C M; Spielman, A; Telford, S R

    1995-01-01

    To determine whether protective immunity against the agent of Lyme disease may be expressed mainly within its tick vector prior to transmission, we passively immunized mice at various intervals after infected ticks had attached, and assayed such mice for evidence of spirochetal infection by xenodiagnosis one month after challenge. Groups of CD-1 mice were intraperitoneally infused with 0.5 ml of hyperimmune rabbit or mouse serum, reagents and quantities previously determined to protect against syringe-challenge with 10(6) low-passage JD1 spirochetes 12 hr after passive transfer. Comparison groups received normal rabbit serum or saline. All mice were protected from infection when infused no more than one day after infective ticks were allowed to attach. However, if infused three or five days post-tick attachment, 60-100% of the mice became infected. All mice became persistently infected when infused with saline or normal rabbit serum. We conclude that antibody is protective against tick-transmitted spirochetal infection only when passively administered before the spirochetes are deposited in the skin of the host. Ingested antibody may destroy spirochetes or interfere with activation and replication within the tick gut, or with dissemination to the salivary glands. Lyme disease vaccines may thus be uniquely effective because of the vulnerability of the spirochetal agent within its vector.

  3. Borrelia burgdorferi stimulates macrophages to secrete higher levels of cytokines and chemokines than Borrelia afzelii or Borrelia garinii.

    PubMed

    Strle, Klemen; Drouin, Elise E; Shen, Shiqian; El Khoury, Joseph; McHugh, Gail; Ruzic-Sabljic, Eva; Strle, Franc; Steere, Allen C

    2009-12-15

    To delineate the inflammatory potential of the 3 pathogenic species of Borrelia burgdorferi sensu lato, we stimulated monocyte-derived macrophages from healthy human donors with 10 isolates each of B. burgdorferi, Borrelia afzelii, or Borrelia garinii recovered from erythema migrans skin lesions of patients with Lyme borreliosis from the United States or Slovenia. B. burgdorferi isolates from the United States induced macrophages to secrete significantly higher levels of interleukin (IL)-8, CCL3, CCL4, IL-6, IL-10, and tumor necrosis factor than B. garinii or B. afzelii isolates. Consistent with this response in cultured macrophages, chemokine and cytokine levels in serum samples of patients from whom the isolates were obtained were significantly greater in B. burgdorferi-infected patients than in B. afzelii- or B. garinii-infected patients. These results demonstrate in vitro and in vivo that B. burgdorferi has greater inflammatory potential than B. afzelii and B. garinii, which may account in part for variations in the clinical manifestations of Lyme borreliosis.

  4. [Criteria for evaluation of immunoblots using Borrelia afzelii, Borrelia garinii and Borrelia burgdorferi sensu stricto for diagnosis of Lyme borreliosis].

    PubMed

    Honegr, K; Havlasová, J; Gebouský, P; Dostál, V; Pellantová, V; Skrabková, Z; Hulínská, D

    2001-11-01

    The immunoblot was prepared from genotypes Borrelia afzelii (KC 90), Borrelia garinii (M 192) and Borrelia burgdorferi sensu stricto (B 31). Sera of 63 patients with different forms of Lyme borreliosis were examined and 40 healthy donors in the endemic area of the disease. In class IgM in the group of patients significantly more frequently antibodies against OspC, p39, p41 B. afzelii, p39, p41, p66, p83 B. garinii and OspC1, OspA, B. burgdorferi sensu stricto were found. In class IgG there were antibodies against p39, p41, p93 B. afzelii, p14, p41, p93 B. garinii and OspA, OspC p93 B. burgdorferi sensu lato. Based on the assembled results by means of discrimination analysis and logistic regression the most suitable combinations of antigens for evaluation of immunoblots in different genotypes were determined. Furthermore evaluation was suggested using a combination of antigens of several genotypes which led to an increased sensitivity and specificity of the immunoblot. Tables were prepared for easier evaluation of newly examined sera samples.

  5. [Heterogeneity of the gene P83/100 of Borrelia borrelia burgdorferi sensu lato complex].

    PubMed

    Fomenko, N V; Sabitova, Iu B; Khasnatinov, M A; Gol'tsova, N A; Danchinova, G A; Bataa, Zh; Ambed, D; Stronin, O V

    2007-01-01

    The 35 full-length Borrelia burgdorferi sensu lato complex a83/100 gene nucleotide sequences were determined. High level of homology was observed in the nucleotide sequences corresponding to the strains and isolates of Borrelia fzelii. The analysis of the nucleotide sequences revealed two groups of Borrelia garinii. The most variable p83/100 gene region containing species-typical insertions and deletions was demonstrated to be included into the region where the antigenic determinants of protein were encoded. According to the data obtained in this work, the modification of the P83/100 protein structure and immunological properties could be suggested to exist even within species. The results of this work could be used for receiving recombinant P83/100 proteins useful for diagnostic applications.

  6. [Typhoid fever].

    PubMed

    Marchou, B

    1996-01-15

    Endemic in regions with poor hygienic conditions, Enteric fevers are imported in France by returning travellers. They are caused by Salmonella strains, mainly S. Typhi, transmitted via fecal-oral route. Salmonella reach the blood stream after proliferating in mesenteric lymph nodes. At an initial stage blood and bone marrow cultures, later on Widal-Felix serology permit diagnosis. Antibiotics have rendered death exceptional. Quinolones and ceftriaxone allow treatments shorter than 10 days. Immunization (Typhim Vi) and improvement of hygienic standards are the cornerstone of prevention.

  7. Assessment of the geographic distribution of Ornithodoros turicata (Argasidae): climate variation and host diversity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ornithodoros turicata is an argasid, or soft tick of medical and veterinary importance because it is a known vector of the relapsing fever spirochete, Borrelia turicatae, and potentially African swine fever virus. Historic collections of O. turicata have been recorded from Latin America to the south...

  8. Is Localized Scleroderma Caused by Borrelia burgdorferi?

    PubMed

    Zinchuk, Alexander N; Kalyuzhna, Lidiya D; Pasichna, Iryna A

    2016-09-01

    Despite considerable achievements in the study of localized scleroderma, the etiology of the disease has not been investigated completely. Borrelia burgdorferi-the agent of Lyme disease-is suggested to be one of the possible etiological factors of localized scleroderma. However, among scientists, this hypothesis is quite controversial. We have conducted investigations of the level of IgM and IgG class antibodies to B. burgdorferi in the serum of patients with localized scleroderma. To rationally substantiate the role of B. burgdorferi in the occurrence of localized scleroderma, thirty-two patients with localized scleroderma treated at an in-patient department were examined. The level of anti-Borrelia antibodies was determined in ELISA. Diagnostic levels of IgM and/or IgG were detected in 18.8% of patients with localized scleroderma, which is more than in the population (p < 0.01). Positive levels of anti-Borrelia antibodies in patients with localized scleroderma confirm the borreliosis nature of the disease, requiring conduction of complex antimicrobial treatment. PMID:27387068

  9. Dengue hemorrhagic fever

    MedlinePlus

    Hemorrhagic dengue; Dengue shock syndrome; Philippine hemorrhagic fever; Thai hemorrhagic fever; Singapore hemorrhagic fever ... and sweaty. These symptoms are followed by a shock -like state. Bleeding appears as tiny spots of ...

  10. Antibody to a 39-kilodalton Borrelia burgdorferi antigen (P39) as a marker for infection in experimentally and naturally inoculated animals.

    PubMed Central

    Simpson, W J; Burgdorfer, W; Schrumpf, M E; Karstens, R H; Schwan, T G

    1991-01-01

    Borrelia burgdorferi expresses a conserved, species-specific 39-kDa protein (P39) that can stimulate antibodies during human infection. To confirm that anti-P39 antibodies are produced consistently in animals exposed to infectious spirochetes, white-footed mice, Peromyscus leucopus, and laboratory white mice, Mus musculus (strain BALB/c), were experimentally inoculated with either infectious or noninfectious B. burgdorferi and the antibody response to P39 was determined by immunoblot at 21 days postinoculation. All mice inoculated with approximately 10(7) infectious B. burgdorferi produced anti-P39 antibodies and were cultured positive for this spirochete. Mice inoculated with similar numbers of inactivated or viable noninfectious B. burgdorferi still producing P39 did not induce anti-P39 antibodies. By contrast, putative antiflagellin antibodies were detected in less than 18% of the infected animals, which supports the notion that antibody reactive with flagellin may not be reliable as a marker for B. burgdorferi exposure as was originally thought. Mice infected with B. burgdorferi following exposure to ticks (Ixodes dammini) produced anti-P39 antibodies no later than 7 days postinfection, indicating that P39 is an effective immunogen in natural infections. Notably, anti-P39 antibodies were the predominant B. burgdorferi reactive antibodies detected early in the infection. Our results indicate that anti-P39 antibodies are produced in response to an active infection and are therefore reliable markers for infection in experimentally and naturally inoculated animals. Images PMID:2007630

  11. Persistence of the antibody response to the VlsE sixth invariant region (IR6) peptide of Borrelia burgdorferi after successful antibiotic treatment of Lyme disease.

    PubMed

    Peltomaa, Miikka; McHugh, Gail; Steere, Allen C

    2003-04-15

    It has been suggested that a <4-fold decline in the immunoglobulin G (IgG) antibody response to the VlsE sixth invariant region peptide of Borrelia burgdorferi within 6 months after antibiotic treatment may indicate spirochetal persistence in Lyme disease. We studied the response to this peptide in 77 patients with early or late disease, for whom archival samples were available at the time of antibiotic treatment and approximately 6 months or years later. Eight (33%) of the 24 patients with early manifestations and 18 (86%) of the 21 patients with late manifestations had a <4-fold decline in IgG anti-VlsE titers approximately 6 months after successful antibiotic treatment. Of 32 additional patients, 13 (50%) with early manifestations and 5 (83%) with late manifestations still had positive anti-VlsE titers 8-15 years after successful antibiotic treatment. We conclude that persistence of the anti-VlsE antibody response for months or years after antibiotic treatment cannot be equated with spirochetal persistence in Lyme disease.

  12. Chikungunya fever.

    PubMed

    Kucharz, Eugene J; Cebula-Byrska, Ilona

    2012-06-01

    Chikungunya fever (CF) is an acute illness caused by Chikungunya virus (CHIKV) belonging to the alphavirus genus of the Alphaviruses (Togaviridae) family. The virus is transmitted by Aedes mosquitoes. CF is primarily tropical disease occurring in Africa, Asia and Indian Ocean islands but in the last decade an outbreak of CHIKV autochthonous infections were reported in Italy and France. It is associated with viral genome mutations facilitating transmission of the disease by Aedes albopictus, a mosquito occurring in several European countries. The CF is highly symptomatic, characterized by fever, cutaneuos rash and severe athralgia and arthritis. In some patients severe neurological or hemorrhagic manifestations occur. The disease is self-limiting but a part of the patients suffers from a long-lasting arthritis akin to rheumatoid arthritis. Treatment is only symptomatic. Prevention includes reduction of mosquito bite (mosquito net, repellent) or application of measures against mosquito larvae. Vaccination is not currently available but investigations are in progress. CF presents a significant worldwide health problem affecting in the last decade millions of person, and currently dangerous also for European countries.

  13. CheY3 of Borrelia burgdorferi is the key response regulator essential for chemotaxis and forms a long-lived phosphorylated intermediate.

    PubMed

    Motaleb, M A; Sultan, Syed Z; Miller, Michael R; Li, Chunhao; Charon, Nyles W

    2011-07-01

    Spirochetes have a unique cell structure: These bacteria have internal periplasmic flagella subterminally attached at each cell end. How spirochetes coordinate the rotation of the periplasmic flagella for chemotaxis is poorly understood. In other bacteria, modulation of flagellar rotation is essential for chemotaxis, and phosphorylation-dephosphorylation of the response regulator CheY plays a key role in regulating this rotary motion. The genome of the Lyme disease spirochete Borrelia burgdorferi contains multiple homologues of chemotaxis genes, including three copies of cheY, referred to as cheY1, cheY2, and cheY3. To investigate the function of these genes, we targeted them separately or in combination by allelic exchange mutagenesis. Whereas wild-type cells ran, paused (flexed), and reversed, cells of all single, double, and triple mutants that contained an inactivated cheY3 gene constantly ran. Capillary tube chemotaxis assays indicated that only those strains with a mutation in cheY3 were deficient in chemotaxis, and cheY3 complementation restored chemotactic ability. In vitro phosphorylation assays indicated that CheY3 was more efficiently phosphorylated by CheA2 than by CheA1, and the CheY3-P intermediate generated was considerably more stable than the CheY-P proteins found in most other bacteria. The results point toward CheY3 being the key response regulator essential for chemotaxis in B. burgdorferi. In addition, the stability of CheY3-P may be critical for coordination of the rotation of the periplasmic flagella.

  14. Borrelia burgdorferi s.l. in Ixodes ricinus (Acari: Ixodidae) ticks collected from vegetation and small rodents in recreational areas of the city of Poznań.

    PubMed

    Michalik, Jerzy; Hofman, Teresa; Buczek, Alicja; Skoracki, Maciej; Sikora, Bozena

    2003-09-01

    During 1998-1999, Ixodes ricinus (L.) populations were investigated in three different biotopes (deciduous, mixed, coniferous forest) situated in popular recreational areas in Poznań, Poland. In total, 1,123 questing ticks (1,002 nymphs, 69 males, 52 females) were collected by flagging vegetation. Additionally, in 1998 between May and September small rodents were trapped and inspected for feeding ticks. Altogether, 213 rodents of three species: Apodemus agrarius Pall., A. flavicollis Melchior, Clethrionomys glareolus Schreber were captured. Of 323 engorged ticks, 304 were larvae and 19 nymphs. All ticks collected from vegetation, as well as from rodents were examined for the presence of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigenwalt & Brenner s.l. spirochetes by indirect immunofluorescence assay (IFA) using PAB 1B29. The seasonal pattern of activity of questing I. ricinus was always bimodal (May/June and August/September). The most abundant tick population occurred in the deciduous forest. The total infection rate in questing ticks was 16.2%. Differences in mean infection prevalence of host-seeking ticks between three biotopes each year were not significant. On average more larvae parasitized on the genus of Apodemus than on C. glareolus. 17.8% of larvae and 31.6% of nymphs fed on rodents harbored spirochetes. The three rodent species contributed to a different degree in to transmission of the pathogen to subadult stages. Approximately 27% of larvae infested on A. agrarius, 22% on C. glareolus, and only 4.2% on A. flavicollis contained spirochetes. The results suggest that the prevalence of A. agrarius and C. glareolus in disturbed urban forests used for leisure activities seems to be crucial for the maintenance of B. burgdorferi s.l. in I. ricinus populations.

  15. Exploitation of complement regulatory proteins by Borrelia and Francisella.

    PubMed

    Madar, Marian; Bencurova, Elena; Mlynarcik, Patrik; Almeida, André M; Soares, Renata; Bhide, Katarina; Pulzova, Lucia; Kovac, Andrej; Coelho, Ana V; Bhide, Mangesh

    2015-06-01

    Pathogens have developed sophisticated mechanisms of complement evasion such as binding to the host complement regulatory proteins (CRPs) on their surface or expression of CRP mimicking molecules. The ability of pathogens to evade the complement system has been correlated with pathogenesis and host selectivity. Hitherto, little work has been undertaken to determine whether Borrelia and Francisella exploit various CRPs to block complement attack. Seventeen Borrelia (twelve species) and six Francisella (three subspecies) strains were used to assess their ability to bind human, sheep and cattle CRPs or mimic membrane associated complement regulators. A series of experiments including affinity ligand binding experiments, pull-down assays and mass spectrometry based protein identification, revealed an array of CRP binding proteins of Borrelia and Francisella. Unlike Francisella, Borrelia strains were able to bind multiple human CRPs. Three strains of Borrelia (SKT-4, SKT-2 and HO14) showed the presence of a human CD46-homologous motif, indicating their ability to possess putative human CD46 mimicking molecules. Similarly, five strains of Borrelia and two strains of Francisella may have surface proteins with human CD59-homologous motifs. Among ovine and bovine CRPs, the only CRP bound by Francisella (LVS, Tul4 strain) was vitronectin, while ovine C4BP, ovine factor H and bovine factor H were bound to Borrelia strains SKT-2, DN127 and Co53. This study presents an array of proteins of Borrelia and Francisella that bind CRPs or may mimic membrane-CRPs, thus enabling multiphasic complement evasion strategies of these pathogens.

  16. Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi.

    PubMed

    Salazar, Carlos A; Rothemich, Monika; Drouin, Elise E; Glickstein, Lisa; Steere, Allen C

    2005-05-01

    In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis.

  17. Human Lyme Arthritis and the Immunoglobulin G Antibody Response to the 37-Kilodalton Arthritis-Related Protein of Borrelia burgdorferi

    PubMed Central

    Salazar, Carlos A.; Rothemich, Monika; Drouin, Elise E.; Glickstein, Lisa; Steere, Allen C.

    2005-01-01

    In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis. PMID:15845501

  18. Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex.

    PubMed

    Garcia, Brandon L; Zhi, Hui; Wager, Beau; Höök, Magnus; Skare, Jon T

    2016-01-01

    Pathogens that traffic in blood, lymphatics, or interstitial fluids must adopt strategies to evade innate immune defenses, notably the complement system. Through recruitment of host regulators of complement to their surface, many pathogens are able to escape complement-mediated attack. The Lyme disease spirochete, Borrelia burgdorferi, produces a number of surface proteins that bind to factor H related molecules, which function as the dominant negative regulator of the alternative pathway of complement. Relatively less is known about how B. burgdorferi evades the classical pathway of complement despite the observation that some sensu lato strains are sensitive to classical pathway activation. Here we report that the borrelial lipoprotein BBK32 potently and specifically inhibits the classical pathway by binding with high affinity to the initiating C1 complex of complement. In addition, B. burgdorferi cells that produce BBK32 on their surface bind to both C1 and C1r and a serum sensitive derivative of B. burgdorferi is protected from killing via the classical pathway in a BBK32-dependent manner. Subsequent biochemical and biophysical approaches localized the anti-complement activity of BBK32 to its globular C-terminal domain. Mechanistic studies reveal that BBK32 acts by entrapping C1 in its zymogen form by binding and inhibiting the C1 subcomponent, C1r, which serves as the initiating serine protease of the classical pathway. To our knowledge this is the first report of a spirochetal protein acting as a direct inhibitor of the classical pathway and is the only example of a biomolecule capable of specifically and noncovalently inhibiting C1/C1r. By identifying a unique mode of complement evasion this study greatly enhances our understanding of how pathogens subvert and potentially manipulate host innate immune systems.

  19. Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex

    PubMed Central

    Wager, Beau; Höök, Magnus; Skare, Jon T.

    2016-01-01

    Pathogens that traffic in blood, lymphatics, or interstitial fluids must adopt strategies to evade innate immune defenses, notably the complement system. Through recruitment of host regulators of complement to their surface, many pathogens are able to escape complement-mediated attack. The Lyme disease spirochete, Borrelia burgdorferi, produces a number of surface proteins that bind to factor H related molecules, which function as the dominant negative regulator of the alternative pathway of complement. Relatively less is known about how B. burgdorferi evades the classical pathway of complement despite the observation that some sensu lato strains are sensitive to classical pathway activation. Here we report that the borrelial lipoprotein BBK32 potently and specifically inhibits the classical pathway by binding with high affinity to the initiating C1 complex of complement. In addition, B. burgdorferi cells that produce BBK32 on their surface bind to both C1 and C1r and a serum sensitive derivative of B. burgdorferi is protected from killing via the classical pathway in a BBK32-dependent manner. Subsequent biochemical and biophysical approaches localized the anti-complement activity of BBK32 to its globular C-terminal domain. Mechanistic studies reveal that BBK32 acts by entrapping C1 in its zymogen form by binding and inhibiting the C1 subcomponent, C1r, which serves as the initiating serine protease of the classical pathway. To our knowledge this is the first report of a spirochetal protein acting as a direct inhibitor of the classical pathway and is the only example of a biomolecule capable of specifically and noncovalently inhibiting C1/C1r. By identifying a unique mode of complement evasion this study greatly enhances our understanding of how pathogens subvert and potentially manipulate host innate immune systems. PMID:26808924

  20. DhhP, a Cyclic di-AMP Phosphodiesterase of Borrelia burgdorferi, Is Essential for Cell Growth and Virulence

    PubMed Central

    Ye, Meiping; Zhang, Jun-Jie; Fang, Xin; Lawlis, Gavin B.; Troxell, Bryan; Zhou, Yan; Gomelsky, Mark

    2014-01-01

    Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. Most of work on c-di-AMP signaling has been done in Gram-positive bacteria, firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect potassium transport, cell wall structure, and antibiotic resistance. Little is known about c-di-AMP signaling in other bacteria. Borrelia burgdorferi, the causative agent of Lyme disease, is a spirochete that has a Gram-negative dual membrane. In this study, we demonstrated that B. burgdorferi BB0619, a DHH-DHHA1 domain protein (herein designated DhhP), functions as c-di-AMP phosphodiesterase. Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn2+- or Mg2+-dependent manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP appears to be essential for B. burgdorferi growth both in vitro and in the mammalian host. Inactivation of the chromosomal dhhP gene could be achieved only in the presence of a plasmid-encoded inducible dhhP gene. The conditional dhhP mutant had a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Unlike what has been observed in Gram-positive bacteria, elevated cellular c-di-AMP in B. burgdorferi did not result in an increased resistance to β-lactamase antibiotics, suggesting that c-di-AMP's functions in spirochetes differ from those in Gram-positive bacteria. In addition, the dhhP mutant was defective in induction of the σS factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers an important role of c-di-AMP in B. burgdorferi virulence. PMID:24566626

  1. Dual role for Fcγ receptors in host defense and disease in Borrelia burgdorferi-infected mice

    PubMed Central

    Belperron, Alexia A.; Liu, Nengyin; Booth, Carmen J.; Bockenstedt, Linda K.

    2014-01-01

    Arthritis in mice infected with the Lyme disease spirochete, Borrelia burgdorferi, results from the influx of innate immune cells responding to the pathogen in the joint and is influenced in part by mouse genetics. Production of inflammatory cytokines by innate immune cells in vitro is largely mediated by Toll-like receptor (TLR) interaction with Borrelia lipoproteins, yet surprisingly mice deficient in TLR2 or the TLR signaling molecule MyD88 still develop arthritis comparable to that seen in wild type mice after B. burgdorferi infection. These findings suggest that other, MyD88-independent inflammatory pathways can contribute to arthritis expression. Clearance of B. burgdorferi is dependent on the production of specific antibody and phagocytosis of the organism. As Fc receptors (FcγR) are important for IgG-mediated clearance of immune complexes and opsonized particles by phagocytes, we examined the role that FcγR play in host defense and disease in B. burgdorferi-infected mice. B. burgdorferi-infected mice deficient in the Fc receptor common gamma chain (FcεRγ−/− mice) harbored ~10 fold more spirochetes than similarly infected wild type mice, and this was associated with a transient increase in arthritis severity. While the elevated pathogen burdens seen in B. burgdorferi-infected MyD88−/− mice were not affected by concomitant deficiency in FcγR, arthritis was reduced in FcεRγ−/−MyD88−/− mice in comparison to wild type or single knockout mice. Gene expression analysis from infected joints demonstrated that absence of both MyD88 and FcγR lowers mRNA levels of proteins involved in inflammation, including Cxcl1 (KC), Xcr1 (Gpr5), IL-1beta, and C reactive protein. Taken together, our results demonstrate a role for FcγR-mediated immunity in limiting pathogen burden and arthritis in mice during the acute phase of B. burgdorferi infection, and further suggest that this pathway contributes to the arthritis that develops in B. burgdorferi

  2. The Borrelia burgdorferi telomere resolvase, ResT, anneals ssDNA complexed with its cognate ssDNA-binding protein

    PubMed Central

    Huang, Shu Hui; Kobryn, Kerri

    2016-01-01

    Spirochetes of the genus Borrelia possess unusual genomes that consist in a linear chromosome and multiple linear and circular plasmids. The linear replicons are terminated by covalently closed hairpin ends, referred to as hairpin telomeres. The hairpin telomeres represent a simple solution to the end-replication problem. Deoxyribonucleic acid replication initiates internally and proceeds bidirectionally toward the hairpin telomeres. The telomere resolvase, ResT, forms the hairpin telomeres from replicated telomere intermediates in a reaction with similarities to those promoted by type IB topoisomerases and tyrosine recombinases. ResT has also been shown to possess DNA single-strand annealing activity. We report here that ResT promotes single-strand annealing of both free DNA strands and ssDNA complexed with single-stranded DNA binding protein (SSB). The annealing of complementary strands bound by SSB requires a ResT–SSB interaction that is mediated by the conserved amphipathic C-terminal tail of SSB. These properties of ResT are similar to those demonstrated for the recombination mediator protein, RecO, of the RecF pathway. Borrelia burgdorferi is unusual in lacking identifiable homologs of the RecFOR proteins. We propose that ResT may provide missing RecFOR functions. PMID:27131360

  3. The Borrelia burgdorferi telomere resolvase, ResT, anneals ssDNA complexed with its cognate ssDNA-binding protein.

    PubMed

    Huang, Shu Hui; Kobryn, Kerri

    2016-06-20

    Spirochetes of the genus Borrelia possess unusual genomes that consist in a linear chromosome and multiple linear and circular plasmids. The linear replicons are terminated by covalently closed hairpin ends, referred to as hairpin telomeres. The hairpin telomeres represent a simple solution to the end-replication problem. Deoxyribonucleic acid replication initiates internally and proceeds bidirectionally toward the hairpin telomeres. The telomere resolvase, ResT, forms the hairpin telomeres from replicated telomere intermediates in a reaction with similarities to those promoted by type IB topoisomerases and tyrosine recombinases. ResT has also been shown to possess DNA single-strand annealing activity. We report here that ResT promotes single-strand annealing of both free DNA strands and ssDNA complexed with single-stranded DNA binding protein (SSB). The annealing of complementary strands bound by SSB requires a ResT-SSB interaction that is mediated by the conserved amphipathic C-terminal tail of SSB. These properties of ResT are similar to those demonstrated for the recombination mediator protein, RecO, of the RecF pathway. Borrelia burgdorferi is unusual in lacking identifiable homologs of the RecFOR proteins. We propose that ResT may provide missing RecFOR functions. PMID:27131360

  4. Free-living spirochetes from Cape Cod microbial mats detected by electron microscopy

    NASA Technical Reports Server (NTRS)

    Teal, T. H.; Chapman, M.; Guillemette, T.; Margulis, L.

    1996-01-01

    Spirochetes from microbial mats and anaerobic mud samples collected in salt marshes were studied by light microscopy, whole mount and thin section transmission electron microscopy. Enriched in cellobiose-rifampin medium, selective for Spirochaeta bajacaliforniensis, seven distinguishable spirochete morphotypes were observed. Their diameters ranged from 0.17 micron to > 0.45 micron. Six of these morphotypes came from southwest Cape Cod, Massachusetts: five from Microcoleus-dominated mat samples collected at Sippewissett salt marsh and one from anoxic mud collected at School Street salt marsh (on the east side of Eel Pond). The seventh morphotype was enriched from anoxic mud sampled from the north central Cape Cod, at the Sandy Neck salt marsh. Five of these morphotypes are similar or identical to previously described spirochetes (Leptospira, Spirochaeta halophila, Spirochaeta bajacaliforniensis, Spirosymplokos deltaeiberi and Treponema), whereas the other two have unique features that suggest they have not been previously described. One of the morphotypes resembles Spirosymplokos deltaeiberi (the largest free-living spirochete described), in its large variable diameter (0.4-3.0 microns), cytoplasmic granules, and spherical (round) bodies with composite structure. This resemblance permits its tentative identification as a Sippewissett strain of Spirosymplokos deltaeiberi. Microbial mats samples collected in sterile Petri dishes and stored dry for more than four years yielded many organisms upon rewetting, including small unidentified spirochetes in at least 4 out of 100 enrichments.

  5. [Viral hemorrhagic fever].

    PubMed

    Kager, P A

    1998-02-28

    Viral haemorrhagic fevers, such as Lassa fever and yellow fever, cause tens of thousands of deaths annually outside the Netherlands. The viruses are mostly transmitted by mosquitoes, ticks or via excreta of rodents. Important to travellers are yellow fever, dengue and Lassa and Ebola fever. For yellow fever there is an efficacious vaccine. Dengue is frequently observed in travellers; prevention consists in avoiding mosquito bites, the treatment is symptomatic. Lassa and Ebola fever are extremely rare among travellers; a management protocol can be obtained from the Netherlands Ministry of Health, Welfare and Sports. Diagnostics of a patient from the tropics with fever and haemorrhagic diathesis should be aimed at treatable disorders such as malaria, typhoid fever, rickettsiosis or bacterial sepsis, because the probability of such a disease is much higher than that of Lassa or Ebola fever.

  6. Differences in prevalence of Borrelia burgdorferi and Anaplasma spp. infection among host-seeking Dermacentor occidentalis, Ixodes pacificus, and Ornithodoros coriaceus ticks in northwestern California

    PubMed Central

    Lane, Robert S.; Mun, Jeomhee; Peribáñez, Miguel A.; Fedorova, Natalia

    2010-01-01

    Previous studies revealed that the Pacific Coast tick (Dermacentor occidentalis) is infected occasionally with the agents of Lyme disease (Borrelia burgdorferi) or human granulocytic anaplasmosis (Anaplasma phagocytophilum) and that it is an inefficient experimental vector of B. burgdorferi. The relationship of the pajahuello tick (Ornithodoros coriaceus) to each of these bacterial zoonotic agents has not been reported. The primary bridging vector of both bacterial zoonotic agents to humans is the western black-legged tick (Ixodes pacificus). Because of the spatial and temporal overlap of D. occidentalis and O. coriaceus populations with those of I. pacificus in natural foci of B. burgdorferi and A. phagocytophilum in northwestern California, we conducted field and laboratory studies to determine if the Pacific Coast tick or the pajahuello tick potentially may serve as secondary vectors of either bacterium. Our findings reconfirmed that wild-caught D. occidentalis ticks are infected infrequently with B. burgdorferi or A. phagocytophilum, but some adult ticks from dense woodlands or chaparral were found to contain 2 important veterinary pathogens for the first time (Anaplasma bovis, A. ovis). The high prevalence of A. bovis infection (4.3%, n=185 ticks) within chaparral-derived ticks suggests that D. occidentalis could be an efficient vector of this rickettsia. Experimental attempts to transmit borreliae or Anaplasma spp. that may have been present in >100 wild-caught D. occidentalis adults to naïve rabbits were unsuccessful. Anaplasma spp. were not detected in O. coriaceus, but one (4.3%) of 23 nymphs was infected with B. bissettii. This finding and an antecedent report of a B. burgdorferi-like spirochete from the same tick species demonstrate that O. coriaceus sometimes acquires and transstadially passes Lyme disease group spirochetes. I. pacificus nymphs inhabiting a woodland nidus of B. burgdorferi and A. phagocytophilum had a 5-fold higher prevalence of

  7. Differences in prevalence of Borrelia burgdorferi and Anaplasma spp. infection among host-seeking Dermacentor occidentalis, Ixodes pacificus, and Ornithodoros coriaceus ticks in northwestern California.

    PubMed

    Lane, Robert S; Mun, Jeomhee; Peribáñez, Miguel A; Fedorova, Natalia

    2010-12-01

    Previous studies revealed that the Pacific Coast tick (Dermacentor occidentalis) is infected occasionally with the agents of Lyme disease (Borrelia burgdorferi) or human granulocytic anaplasmosis (Anaplasma phagocytophilum) and that it is an inefficient experimental vector of B. burgdorferi. The relationship of the pajahuello tick (Ornithodoros coriaceus) to each of these bacterial zoonotic agents has not been reported. The primary bridging vector of both bacterial zoonotic agents to humans is the western black-legged tick (Ixodes pacificus). Because of the spatial and temporal overlap of D. occidentalis and O. coriaceus populations with those of I. pacificus in natural foci of B. burgdorferi and A. phagocytophilum in northwestern California, we conducted field and laboratory studies to determine if the Pacific Coast tick or the pajahuello tick potentially may serve as secondary vectors of either bacterium. Our findings reconfirmed that wild-caught D. occidentalis ticks are infected infrequently with B. burgdorferi or A. phagocytophilum, but some adult ticks from dense woodlands or chaparral were found to contain 2 important veterinary pathogens for the first time (Anaplasma bovis, A. ovis). The high prevalence of A. bovis infection (4.3%, n=185 ticks) within chaparral-derived ticks suggests that D. occidentalis could be an efficient vector of this rickettsia. Experimental attempts to transmit borreliae or Anaplasma spp. that may have been present in >100 wild-caught D. occidentalis adults to naïve rabbits were unsuccessful. Anaplasma spp. were not detected in O. coriaceus, but one (4.3%) of 23 nymphs was infected with B. bissettii. This finding and an antecedent report of a B. burgdorferi-like spirochete from the same tick species demonstrate that O. coriaceus sometimes acquires and transstadially passes Lyme disease group spirochetes. I. pacificus nymphs inhabiting a woodland nidus of B. burgdorferi and A. phagocytophilum had a 5-fold higher prevalence of

  8. Genomic Characteristics of Chinese Borrelia burgdorferi Isolates

    PubMed Central

    Hou, Xuexia; Zhang, Lin; Zhang, Yuanyuan; Liu, Huixin; Liu, Wei; Chen, Chen; Wan, Kanglin

    2016-01-01

    In China, B. burgdorferi, B.garinii, B. afzelii and B. yangtze sp. nov have been reported; B.garinii and B. afzelii are the main pathogenic genotypes. But until now only one Chinese strain was reported with whole genome sequence. In order to further understand the genomic characteristics and diversity of Chinese Borrelia strains, 5 isolates from China were sequenced and compared with the whole genome sequences of strains in other areas. The results showed a high degree of conservation within the linear chromosome of Chinese strains, whereas plasmid showed a much larger diversity according to the majority genomic information of plasmids. The genome sequences of the five Chinese strains were compared with the corresponding reference strains, respectively, according to the genospecies. Pairwise analysis demonstrates that there are only 70 SNPs between the genomes of CS4 and B31. However, there are many more SNPs between the genomes of QX-S13 and VS116, PD91 and PBi, FP1 and PKo, R9 and Pko, respectively. Gene comparison showed some important different genes. OspA was one of the important different genes. Comparative genomic studies have found that OspA gene sequences of PD91 and R9 had great differences compared with the sequence of B31. OspA gene sequence of R9 had a 96bp deletion; OspA gene of PD91 had two deletions: 9bp and 10 bp. To conclude, we showed the genomic characteristics of four genotype Chinese B. burgdorferi strains. The genomic sequence of B. yangtze sp. nov and differences from B. valaisiana were first reported. Comparative analysis of Chinese strains with the different Borrelia species from other areas will help us to understand evolution and pathogenesis of Chinese Borrelia burgdorferi strains. PMID:27093540

  9. Spirochetal motility and chemotaxis in the natural enzootic cycle and development of Lyme disease.

    PubMed

    Motaleb, Md A; Liu, Jun; Wooten, R Mark

    2015-12-01

    Two-thirds of all bacterial genomes sequenced to-date possess an organelle for locomotion, referred to as flagella, periplasmic flagella or type IV pili. These genomes may also contain a chemotaxis-signaling system which governs flagellar rotation, thus leading a coordinated function for motility. Motility and chemotaxis are often crucial for infection or disease process caused by pathogenic bacteria. Although motility-associated genes are well-characterized in some organisms, the highly orchestrated synthesis, regulation, and assembly of periplasmic flagella in spirochetes are just being delineated. Recent advances were fostered by development of unique genetic manipulations in spirochetes coupled with cutting-edge imaging techniques. These contemporary advances in understanding the role of spirochetal motility and chemotaxis in host persistence and disease development are highlighted in this review.

  10. Spirochetal motility and chemotaxis in the natural enzootic cycle and development of Lyme disease.

    PubMed

    Motaleb, Md A; Liu, Jun; Wooten, R Mark

    2015-12-01

    Two-thirds of all bacterial genomes sequenced to-date possess an organelle for locomotion, referred to as flagella, periplasmic flagella or type IV pili. These genomes may also contain a chemotaxis-signaling system which governs flagellar rotation, thus leading a coordinated function for motility. Motility and chemotaxis are often crucial for infection or disease process caused by pathogenic bacteria. Although motility-associated genes are well-characterized in some organisms, the highly orchestrated synthesis, regulation, and assembly of periplasmic flagella in spirochetes are just being delineated. Recent advances were fostered by development of unique genetic manipulations in spirochetes coupled with cutting-edge imaging techniques. These contemporary advances in understanding the role of spirochetal motility and chemotaxis in host persistence and disease development are highlighted in this review. PMID:26519910

  11. Sequence analysis and characterization of a 40-kilodalton Borrelia hermsii glycerophosphodiester phosphodiesterase homolog.

    PubMed Central

    Shang, E S; Skare, J T; Erdjument-Bromage, H; Blanco, D R; Tempst, P; Miller, J N; Lovett, M A

    1997-01-01

    We report the purification, molecular cloning, and characterization of a 40-kDa glycerophosphodiester phosphodiesterase homolog from Borrelia hermsii. The 40-kDa protein was solubilized from whole organisms with 0.1% Triton X-100, phase partitioned into the Triton X-114 detergent phase, and purified by fast-performance liquid chromatography (FPLC). The gene encoding the 40-kDa protein was cloned from a B. hermsii chromosomal DNA lambda EXlox expression library and identified by using affinity antibodies generated against the purified native protein. The deduced amino acid sequence included a 20-amino-acid signal peptide encoding a putative leader peptidase II cleavage site, indicating that the 40-kDa protein was a lipoprotein. Based on significant homology (31 to 52% identity) of the 40-kDa protein to glycerophosphodiester phosphodiesterases of Escherichia coli (GlpQ), Bacillus subtilis (GlpQ), and Haemophilus influenzae (Hpd; protein D), we have designated this B. hermsii 40-kDa lipoprotein a glycerophosphodiester phosphodiesterase (Gpd) homolog, the first B. hermsii lipoprotein to have a putative functional assignment. A nonlipidated form of the Gpd homolog was overproduced as a fusion protein in E. coli BL21(DE3)(pLysE) and was used to immunize rabbits to generate specific antiserum. Immunoblot analysis with anti-Gpd serum recognized recombinant H. influenzae protein D, and conversely, antiserum to H. influenzae protein D recognized recombinant B. hermsii Gpd (rGpd), indicating antigenic conservation between these proteins. Antiserum to rGpd also identified native Gpd as a constituent of purified outer membrane vesicles prepared from B. hermsii. Screening of other pathogenic spirochetes with anti-rGpd serum revealed the presence of antigenically related proteins in Borrelia burgdorferi, Treponema pallidum, and Leptospira kirschneri. Further sequence analysis both upstream and downstream of the Gpd homolog showed additional homologs of glycerol metabolism

  12. [Rheumatic fever].

    PubMed

    Cherkashin, D V; Kumchin, A N; Shchulenin, S N; Svistov, A S

    2013-01-01

    This lecture-style paper highlights all major problems pertinent to rheumatic fever Definition of acute RF and chronic rheumatic heart disease is proposed and desirability of the use of these terms in clinical practice is explained. Present-day epidemiology of RF is described with reference to marked differences in its prevalence in developed and developing countries. Modern classification of acute RF is described as adopted by the Russian Association of Rheumatologists and recommended for the use in Russian medical facilities. Discussion of etiological issues is focused on such virulence factors as beta-hemolytic streptococcus A and genetic predisposition confirming hereditary nature of RE Its clinical features are described along with laboratory and instrumental methods applied for its diagnostics. Large and small diagnostic criteria of RF are considered. Special attention is given to the treatment of RF and its complications (antibiotic, pathogenetic, and drug therapy). Its primary and secondary prophylaxis is discussed in detail, preparations for the purpose are listed (with doses and duration of application). In conclusion, criteria for the efficacy of therapy are presented along with indications for hospitalization and emergency treatment. PMID:24437162

  13. Borrelia infection and risk of non-Hodgkin lymphoma

    PubMed Central

    Melbye, Mads; Munksgaard, Lars; Smedby, Karin Ekström; Rostgaard, Klaus; Glimelius, Bengt; Chang, Ellen T.; Roos, Göran; Hansen, Mads; Adami, Hans-Olov; Hjalgrim, Henrik

    2008-01-01

    Reports of the presence of Borrelia burgdorferi DNA in malignant lymphomas have raised the hypothesis that infection with B burgdorferi may be causally related to non-Hodgkin lymphoma (NHL) development. We conducted a Danish-Swedish case-control study including 3055 NHL patients and 3187 population controls. History of tick bite or Borrelia infection was ascertained through structured telephone interviews and through enzyme-linked immunosorbent assay serum analyses for antibodies against B burgdorferi in a subset of 1579 patients and 1358 controls. Statistical associations with risk of NHL, including histologic subtypes, were assessed by logistic regression. Overall risk of NHL was not associated with self-reported history of tick bite (odds ratio [OR] = 1.0; 95% confidence interval: 0.9-1.1), Borrelia infection (OR = 1.3 [0.96-1.8]) or the presence of anti-Borrelia antibodies (OR = 1.3 [0.9-2.0]). However, in analyses of NHL subtypes, self-reported history of B burgdorferi infection (OR = 2.5 [1.2-5.1]) and seropositivity for anti-Borrelia antibodies (OR = 3.6 [1.8-7.4]) were both associated with risk of mantle cell lymphoma. Notably, this specific association was also observed in persons who did not recall Borrelia infection yet tested positive for anti-Borrelia antibodies (OR = 4.2 [2.0-8.9]). Our observations suggest a previously unreported association between B burgdorferi infection and risk of mantle cell lymphoma. PMID:18424667

  14. T helper cell priming of mice to Borrelia burgdorferi OspA leads to induction of protective antibodies following experimental but not tick-borne infection.

    PubMed

    Zhong, W; Gern, L; Kramer, M; Wallich, R; Simon, M M

    1997-11-01

    Antibodies to the outer surface lipoprotein A (OspA) of Borrelia burgdorferi confer protection to SCID mice against subsequent tick-borne or experimental infection. However, OspA-specific antibodies are hardly detectable in naturally infected humans, dogs, hamsters and mice. This is most probably due to limited expression of OspA on spirochetes transmitted from the vector to the host. Here we have tested whether T cell priming of mice would lead to the induction of protective OspA-specific antibodies upon infection. It is shown that AKR/N mice, previously immunized with either a single T helper cell peptide of OspA, or a mixture of 27 peptides spanning the entire molecule, develop OspA-specific IgM or IgG antibodies, including those to a prominent protective B cell epitope of OspA. LA-2, within 7 days of infection with low doses (10(3)) of culture-derived spirochetes. In marked contrast, the same groups of pre-sensitized mice failed to generate any detectable OspA-specific antibodies after tick-borne infection for more than 40 days after infection. All mice, irrespective of their state of T cell immunity to OspA or the mode of infection, produced similar levels of OspC-specific IgM and IgG antibodies as early as day 14 after infection. None of the mice previously immunized with OspA peptides were protected against experimental infection, in spite of the appearance of protective antibodies. It is clear from these data that, in contrast to culture-derived spirochetes, the naturally transmitted pathogen fails to express OspA within the mammalian host at levels sufficient for induction of B cell responses, even in the presence of pre-activated T helper cells. Together with the fact that OspA-specific antibodies are mainly operative by eliminating spirochetes from the vector during infestation, the data suggest that OspA-vaccination for T helper cell immunity alone is not sufficient to prevent Lyme disease.

  15. The lipid raft proteome of Borrelia burgdorferi.

    PubMed

    Toledo, Alvaro; Pérez, Alberto; Coleman, James L; Benach, Jorge L

    2015-11-01

    Eukaryotic lipid rafts are membrane microdomains that have significant amounts of cholesterol and a selective set of proteins that have been associated with multiple biological functions. The Lyme disease agent, Borrelia burgdorferi, is one of an increasing number of bacterial pathogens that incorporates cholesterol onto its membrane, and form cholesterol glycolipid domains that possess all the hallmarks of eukaryotic lipid rafts. In this study, we isolated lipid rafts from cultured B. burgdorferi as a detergent resistant membrane (DRM) fraction on density gradients, and characterized those molecules that partitioned exclusively or are highly enriched in these domains. Cholesterol glycolipids, the previously known raft-associated lipoproteins OspA and OpsB, and cholera toxin partitioned into the lipid rafts fraction indicating compatibility with components of the DRM. The proteome of lipid rafts was analyzed by a combination of LC-MS/MS or MudPIT. Identified proteins were analyzed in silico for parameters that included localization, isoelectric point, molecular mass and biological function. The proteome provided a consistent pattern of lipoproteins, proteases and their substrates, sensing molecules and prokaryotic homologs of eukaryotic lipid rafts. This study provides the first analysis of a prokaryotic lipid raft and has relevance for the biology of Borrelia, other pathogenic bacteria, as well as for the evolution of these structures. All MS data have been deposited in the ProteomeXchange with identifier PXD002365 (http://proteomecentral.proteomexchange.org/dataset/PXD002365).

  16. Borrelia burgdorferi Sensu Lato in Siberian chipmunks (Tamias sibiricus) introduced in suburban forests in France.

    PubMed

    Vourc'h, Gwenaël; Marmet, Julie; Chassagne, Michelle; Bord, Séverine; Chapuis, Jean-Louis

    2007-01-01

    Numerous vertebrate reservoirs have been described for Borrelia burgdorferi sensu lato (sl), which includes the etiological agents of Lyme Borreliosis (LB). The Siberian chipmunk (Tamias sibiricus) is a rodent originating from Asia, where it is suspected to be a B. burgdorferi reservoir. It has been intentionally released into the wild in Europe since the 1970s, but has not yet been subject to any study regarding its association with the LB agent. In this paper we studied Siberian chipmunk infestation with the LB vector (Ixodes ricinus) and infection prevalence by LB spirochetes in a suburban introduced population. We compared these findings with known competent reservoir hosts, the bank vole (Myodes [clethrionomys] glareolus) and wood mouse (Apodemus sylvaticus). All Siberian chipmunks were infested with larvae and larval abundance was higher in this species (mean number of larvae [95% Confidence Interval]: 73.5 [46.0, 117.2]) than in the two other rodent species (bank voles: 4.4 [3.0, 6.3] and wood mice: 10.2 [4.9, 21.2]). Significant factors affecting abundance of larvae were host species and sampling season. Nymphs were most prevalent on chipmunks (86.2%, mean: 5.1 [3.3, 8.0]), one vole carried only two nymphs, and none of the mice had any nymphs. Nymph abundance in chipmunks was affected by sampling season and sex. Furthermore, the infection prevalence of B. burgdorferi sl in the Siberian chipmunk was the highest (33.3%) and predominantly of B. afzelii. The infection prevalence was 14.1% in bank voles, but no wood mouse was found to be infected. Our results suggest that the Siberian chipmunk may be an important reservoir host for LB.

  17. Evaluation of the Borrelia burgdorferi BBA64 Protein as a Protective Immunogen in Mice

    PubMed Central

    Brandt, Kevin S.; Patton, Toni G.; Allard, Anna S.; Caimano, Melissa J.; Radolf, Justin D.

    2014-01-01

    The Borrelia burgdorferi bba64 gene product is a surface-localized lipoprotein synthesized within mammalian and tick hosts and is involved in vector transmission of disease. These properties suggest that BBA64 may be a vaccine candidate against Lyme borreliosis. In this study, protective immunity against B. burgdorferi challenge was assessed in mice immunized with the BBA64 protein. Mice developed a high-titer antibody response following immunization with soluble recombinant BBA64 but were not protected when challenged by needle inoculation of culture-grown spirochetes. Likewise, mice passively immunized with an anti-BBA64 monoclonal antibody were not protected against needle-inoculated organisms. BBA64-immunized mice were subjected to B. burgdorferi challenge by the natural route of a tick bite, but these trials did not demonstrate significant protective immunity in either outbred or inbred strains of mice. Lipidated recombinant BBA64 produced in Escherichia coli was assessed for possible improved elicitation of a protective immune response. Although inoculation with this antigen produced a high-titer antibody response, the lipidated BBA64 also was unsuccessful in protecting mice from B. burgdorferi challenge by tick bites. Anti-BBA64 antibodies raised in rats eradicated the organisms, as evidenced by in vitro borreliacidal assays, thus demonstrating the potential for BBA64 to be effective as a protective immunogen. However, passive immunization with the same monospecific rat anti-BBA64 polyclonal serum failed to provide protection against tick bite-administered challenge. These results reveal the challenges faced in not only identifying B. burgdorferi proteins with potential protective capability but also in producing recombinant antigens conducive to preventive therapies against Lyme borreliosis. PMID:24501342

  18. Human homologues of a Borrelia T cell epitope associated with antibiotic-refractory Lyme arthritis.

    PubMed

    Drouin, Elise E; Glickstein, Lisa; Kwok, William W; Nepom, Gerald T; Steere, Allen C

    2008-01-01

    Antibiotic-refractory Lyme arthritis, which may result from infection-induced autoimmunity, is associated with HLA-DR molecules that bind an epitope of Borrelia burgdorferi (Bb) outer-surface protein A (OspA(165-173)) and with T cell reactivity with this epitope. One potential mechanism to explain these associations is molecular mimicry between OspA(165-173) and a self-peptide. Here, we searched the published human genome for peptides with sequence homology with OspA(165-173). The two peptides identified with the greatest sequence homology with the OspA epitope were MAWD-BP(276-288), which had identity at eight of the nine core amino acid residues, and T-span7(58-70), which had identity at six residues. MAWD-BP mRNA was expressed by synoviocytes, while T-span7 mRNA was not. However, neither peptide bound all of the HLA-DR molecules associated with antibiotic-refractory Lyme arthritis. Among 11 patients, 9 had T cell reactivity with OspA(161-170), 6 had responses to MAWD-BP(276-288), and 3 had reactivity with T-span7(58-70), but reactivity with the self-peptides was lower than that induced by the spirochetal epitope. Thus, there remains an association between OspA(165-173) and antibiotic-refractory Lyme arthritis, and infection-induced autoimmunity is an attractive hypothesis to explain this outcome. However, molecular mimicry due to sequence homology between OspA(165-173) and a human peptide seems unlikely to be the critical mechanism.

  19. Human Homologues of a Borrelia T cell Epitope Associated with Antibiotic-Refractory Lyme Arthritis

    PubMed Central

    Drouin, Elise E.; Glickstein, Lisa; Kwok, William W.; Nepom, Gerald T.; Steere, Allen C.

    2007-01-01

    Antibiotic-refractory Lyme arthritis, which may result from infection-induced autoimmunity, is associated with HLA-DR molecules that bind an epitope of Borrelia burgdorferi (Bb) outer-surface protein A (OspA165−173) and with T cell reactivity with this epitope. One potential mechanism to explain these associations is molecular mimicry between OspA165−173 and a self-peptide. Here, we searched the published human genome for peptides with sequence homology with OspA165−173. The two peptides identified with the greatest sequence homology with the OspA epitope were MAWD-BP276−288, which had identity at eight of the nine core amino acid residues, and T-span758−70, which had identity at six residues. MAWD-BP mRNA was expressed by synoviocytes, while T-span7 mRNA was not. However, neither peptide bound all of the HLA-DR molecules associated with antibiotic-refractory Lyme arthritis. Among 11 patients, nine had T cell reactivity with OspA161−170, six had responses to MAWD-BP276−288, and three had reactivity with T-span758−70, but reactivity with the self-peptides was lower than that induced by the spirochetal epitope. Thus, there remains an association between OspA165−173 and antibiotic-refractory Lyme arthritis, and infection-induced autoimmunity is an attractive hypothesis to explain this outcome. However, molecular mimicry due to sequence homology between OspA165−173 and a human peptide seems unlikely to be the critical mechanism. PMID:17555819

  20. Induction of Host Matrix Metalloproteinases by Borrelia burgdorferi Differs in Human and Murine Lyme Arthritis

    PubMed Central

    Behera, Aruna K.; Hildebrand, Ethan; Scagliotti, Joanna; Steere, Allen C.; Hu, Linden T.

    2005-01-01

    Matrix metalloproteinases (MMPs) are induced from host tissues in response to Borrelia burgdorferi. Upregulation of MMPs may play a role in the dissemination of the organism through extracellular matrix tissues, but it can also result in destructive pathology. Although mice are a well-accepted model for Lyme arthritis, there are significant differences compared to human disease. We sought to determine whether MMP expression could account for some of these differences. MMP expression patterns following B. burgdorferi infection were analyzed in primary human chondrocytes, synovial fluid samples from patients with Lyme arthritis, and cartilage tissue from Lyme arthritis-susceptible and -resistant mice by using a gene array, real-time PCR, an enzyme-linked immunosorbent assay, and immunohistochemistry. B. burgdorferi infection significantly induced transcription of MMP-1, -3, -13, and -19 from primary human chondrocyte cells. Transcription of MMP-10 and tissue inhibitor of metalloprotease 1 was increased with B. burgdorferi infection, but protein expression was only minimally increased. The synovial fluid levels of MMPs from patients with high and low spirochete burdens were consistent with results seen in the in vitro studies. B. burgdorferi-susceptible C3H/HeN mice infected with B. burgdorferi showed induction of MMP-3 and MMP-19 but no other MMP or tissue inhibitor of metalloprotease. As determined by immunohistochemistry, MMP-3 expression was increased only in chondrocytes near the articular surface. The levels of MMPs were significantly lower in the more Lyme arthritis-resistant BALB/c and C57BL/6 mice. Differences between human and murine Lyme arthritis may be related to the lack of induction of collagenases, such MMP-1 and MMP-13, in mouse joints. PMID:15618147

  1. BB0744 Affects Tissue Tropism and Spatial Distribution of Borrelia burgdorferi.

    PubMed

    Wager, Beau; Shaw, Dana K; Groshong, Ashley M; Blevins, Jon S; Skare, Jon T

    2015-09-01

    Borrelia burgdorferi, the etiologic agent of Lyme disease, produces a variety of proteins that promote survival and colonization in both the Ixodes species vector and various mammalian hosts. We initially identified BB0744 (also known as p83/100) by screening for B. burgdorferi strain B31 proteins that bind to α1β1 integrin and hypothesized that, given the presence of a signal peptide, BB0744 may be a surface-exposed protein. In contrast to this expectation, localization studies suggested that BB0744 resides in the periplasm. Despite its subsurface location, we were interested in testing whether BB0744 is required for borrelial pathogenesis. To this end, a bb0744 deletion was isolated in a B. burgdorferi strain B31 infectious background, complemented, and queried for the role of BB0744 following experimental infection. A combination of bioluminescent imaging, cultivation of infected tissues, and quantitative PCR (qPCR) demonstrated that Δbb0744 mutant B. burgdorferi bacteria were attenuated in the ability to colonize heart tissue, as well as skin locations distal to the site of infection. Furthermore, qPCR indicated a significantly reduced spirochetal load in distal skin and joint tissue infected with Δbb0744 mutant B. burgdorferi. Complementation with bb0744 restored infectivity, indicating that the defect seen in Δbb0744 mutant B. burgdorferi was due to the loss of BB0744. Taken together, these results suggest that BB0744 is necessary for tissue tropism, particularly in heart tissue, alters the ability of B. burgdorferi to disseminate efficiently, or both. Additional studies are warranted to address the mechanism employed by BB0744 that alters the pathogenic potential of B. burgdorferi.

  2. Rrp2, a prokaryotic enhancer-like binding protein, is essential for viability of Borrelia burgdorferi.

    PubMed

    Groshong, Ashley M; Gibbons, Nora E; Yang, X Frank; Blevins, Jon S

    2012-07-01

    The Lyme disease spirochete, Borrelia burgdorferi, exists in two diverse niches (i.e., an arthropod tick vector and mammalian host) during its enzootic life cycle. To effectively adapt to these unique environments, the bacterium alters the expression of numerous genes, including several major outer surface (lipo)proteins that are required for infection and transmission. An enhancer-binding protein (EBP), known as Rrp2, is one identified activator of the RpoN/RpoS alternative sigma factor cascade. Because initial efforts to generate an rrp2 deletion strain were unsuccessful, the role of Rrp2 in the activation of the RpoN/RpoS pathway was first defined using a strain of B. burgdorferi carrying an rrp2 point mutant that was defective in its ability to activate RpoN-dependent transcription. The fact that subsequent attempts to disrupt rrp2 have also been unsuccessful has led investigators to hypothesize that Rrp2 has other undefined functions which are essential for B. burgdorferi survival and independent of its EBP function. We used a lac-based inducible expression system to generate a conditional rrp2 mutant in virulent B. burgdorferi. In this strain, an isopropyl-β-D-thiogalactopyranoside-inducible copy of the rrp2 gene is expressed in trans from a borrelial shuttle vector. We found that the chromosomal copy of rrp2 could be inactivated only when rrp2 was induced, and the maintenance of rrp2 expression was required for the growth of the mutants. In addition, the overexpression of rrp2 is detrimental to B. burgdorferi growth in a manner that is independent of the RpoN/RpoS pathway. These studies provide the first direct evidence that rrp2 is an essential gene in B. burgdorferi.

  3. First record of Borrelia burgdorferi B31 strain in Dermacentor nitens ticks in the northern region of Parana (Brazil)

    PubMed Central

    Gonçalves, Daniela Dib; Carreira, Teresa; Nunes, Mónica; Benitez, Aline; Lopes-Mori, Fabiana Maria Ruiz; Vidotto, Odilon; de Freitas, Julio Cesar; Vieira, Maria Luísa

    2013-01-01

    The aim of this study was to investigate the presence of DNA of Borrelia burgdorferi sensu lato (s.l.) in ticks that feed on horses used for animal traction in rural Jataizinho, Parana, Brazil. Between February and June 2008, a total of 224 ticks was collected of which 75% were identified as Dermacentor nitens and 25% as Amblyomma cajenense. To amplify B. burgdorferi s.l. DNA, the intergenic space region (ISR) between the 5S (rrf) 23S (rrl) rRNA genes was used as targets for nested-PCR. Two ticks of the D. nitens species were positive for B. burgdorferi s.l. Both species showed a fragment of 184 bp, but the sequencing revealed 99.9% homology with the B. burgdorferi sensu stricto (s.s.) strain B31. These results showed, for the first time, the presence of spirochete DNA infecting ticks that parasitize horses used for animal traction, in the rural municipality mentioned. In conclusion, this study opens up promising prospects for determining the infection rate of B. burgdorferi s.s. genospecies or other species in the equine population, as well as the impact of the infection rate on Lyme disease in the state of Parana. PMID:24516456

  4. Soluble proteins isolated from Borrelia burgdorferi by extraction with Triton X-114 confer resistance to experimental infection.

    PubMed

    Rao, T D; Frey, A B

    1998-10-01

    Fractionation of Borrelia burgdorferi was made by extraction of infectious spirochetes using the detergent Triton X-114. Gel electrophoresis analysis of hydrophilic and hydrophobic proteins demonstrated that detergent extraction resulted in two populations of proteins with nonoverlapping electrophoretic profiles. Immunoblot analysis with monoclonal antibodies reactive with two abundant membrane proteins demonstrated that hydrophilic proteins were uncontaminated with hydrophobic proteins. In addition, assay of thymidine incorporation into and secretion of tumor necrosis factor-alpha from splenocytes cocultured in vitro with either detergent or aqueous phase proteins showed that lymphocyte mitogenic and macrophage activation activities of B. burgdorferi were completely absent from the hydrophilic phase proteins. The Triton X-114 aqueous and detergent phase proteins were used to immunize BALB/c and separately microMT/microMT (B cell knockout) mice that were subsequently challenged with infectious B. burgdorferi. The hydrophilic phase proteins were able to induce protective resistance to infection in either strain of mice demonstrating that potential candidate vaccine antigens are contained in the biochemical class of antigens which is devoid of both lymphocyte mitogen activity and major outer surface proteins. Furthermore, the ability to vaccinate B cell knockout mice suggests that the humoral antispirochete immune response is not the exclusive basis for protective immunity.

  5. Lipopeptides of Borrelia burgdorferi outer surface proteins induce Th1 phenotype development in alphabeta T-cell receptor transgenic mice.

    PubMed Central

    Infante-Duarte, C; Kamradt, T

    1997-01-01

    Induction of the appropriate T helper cell (Th) subset is crucial for the resolution of infectious diseases and the prevention of immunopathology. Some pathogens preferentially induce Th1 or Th2 responses. How microorganisms influence Th phenotype development is unknown. We asked if Borrelia burgdorferi, the spirochete which causes Lyme arthritis, can promote a cytokine milieu in which T cells which are not specific for B. burgdorferi are induced to produce proinflammatory cytokines. Using alphabeta T-cell receptor transgenic mice as a source of T cells with a defined specificity other than for B. burgdorferi, we found that B. burgdorferi induced Th1 phenotype development in ovalbumin-specific transgenic T cells. Small synthetic lipopeptides corresponding to the N-terminal sequences of B. burgdorferi outer surface lipoproteins had similar effects. B. burgdorferi and its lipopeptides induced host cells to produce interleukin-12. When the peptides were used in delipidated form, they did not induce Th1 development. These findings may be of pathogenic importance, since it is currently assumed that a Th2-mediated antibody response is protective against B. burgdorferi. Bacteria associated with reactive arthritis, namely, Yersinia enterocolitica, Shigella flexneri, and Salmonella enteritidis, had different effects. The molecular definition of pathogen-host interactions determining cytokine production should facilitate rational therapeutic interventions directing the host response towards the desired cytokine response. Here, we describe small synthetic molecules capable of inducing Th1 phenotype development. PMID:9317013

  6. Cellular and humoral immune responses to Borrelia burgdorferi antigens in patients with culture-positive early Lyme disease.

    PubMed

    Vaz, A; Glickstein, L; Field, J A; McHugh, G; Sikand, V K; Damle, N; Steere, A C

    2001-12-01

    We determined cellular and humoral immune responses to Borrelia burgdorferi lysate and to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 culture-positive patients with erythema migrans and in 20 healthy control subjects. During the acute illness, a median of 4 days after the onset of erythema migrans, 51% of the patients had proliferative cellular responses and 72% had antibody responses to at least one of the borrelial antigens tested. During convalescence, at the conclusion of antibiotic therapy, 64% of the patients had proliferative cellular reactivity and 95% had antibody reactivity with at least one of the spirochetal antigens tested. In both acute- and convalescent-phase samples, cellular immune responses were found as frequently to OspA as to OspC and FlaB. Although antibody responses were also frequently seen to OspC and FlaB, only a few patients had marginal antibody reactivity with OspA. The percentage of patients with proliferative responses was similar in those with clinical evidence of localized or disseminated infection, whereas humoral reactivity was found more often in those with disseminated disease. We conclude that cellular and humoral responses to B. burgdorferi antigens are often found among patients with early Lyme disease. In contrast with the other antigens tested, cellular but not humoral reactivity was often found with OspA.

  7. Cellular and Humoral Immune Responses to Borrelia burgdorferi Antigens in Patients with Culture-Positive Early Lyme Disease

    PubMed Central

    Vaz, Austin; Glickstein, Lisa; Field, Jodie A.; McHugh, Gail; Sikand, Vijay K.; Damle, Nitin; Steere, Allen C.

    2001-01-01

    We determined cellular and humoral immune responses to Borrelia burgdorferi lysate and to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 culture-positive patients with erythema migrans and in 20 healthy control subjects. During the acute illness, a median of 4 days after the onset of erythema migrans, 51% of the patients had proliferative cellular responses and 72% had antibody responses to at least one of the borrelial antigens tested. During convalescence, at the conclusion of antibiotic therapy, 64% of the patients had proliferative cellular reactivity and 95% had antibody reactivity with at least one of the spirochetal antigens tested. In both acute- and convalescent-phase samples, cellular immune responses were found as frequently to OspA as to OspC and FlaB. Although antibody responses were also frequently seen to OspC and FlaB, only a few patients had marginal antibody reactivity with OspA. The percentage of patients with proliferative responses was similar in those with clinical evidence of localized or disseminated infection, whereas humoral reactivity was found more often in those with disseminated disease. We conclude that cellular and humoral responses to B. burgdorferi antigens are often found among patients with early Lyme disease. In contrast with the other antigens tested, cellular but not humoral reactivity was often found with OspA. PMID:11705918

  8. Borrelia burgdorferi RevA Significantly Affects Pathogenicity and Host Response in the Mouse Model of Lyme Disease

    PubMed Central

    Byram, Rebecca; Gaultney, Robert A.; Floden, Angela M.; Hellekson, Christopher; Stone, Brandee L.; Bowman, Amy; Stevenson, Brian; Johnson, Barbara J. B.

    2015-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, with increased fibrotic collagen deposition in tibiotarsal joints. The mutants also induced increased levels of the chemokine CCL2, a monocyte chemoattractant, in serum, and this increase was abolished in the complemented strain. Therefore, while revA is not absolutely essential for infection, deletion of revA had distinct effects on dissemination, arthritis severity, and host response. PMID:26150536

  9. A tightly regulated surface protein of Borrelia burgdorferi is not essential to the mouse-tick infectious cycle.

    PubMed

    Stewart, Philip E; Bestor, Aaron; Cullen, Jonah N; Rosa, Patricia A

    2008-05-01

    Borrelia burgdorferi synthesizes a variety of differentially regulated outer surface lipoproteins in the tick vector and in vertebrate hosts. Among these is OspD, a protein that is highly induced in vitro by conditions that mimic the tick environment. Using genetically engineered strains in which ospD is deleted, we demonstrate that this protein is not required for B. burgdorferi survival and infectivity in either the mouse or the tick. However, examination of both transcript levels and protein expression indicates that OspD expression is limited to a discrete window of time during B. burgdorferi replication within the tick. This time frame corresponds to tick detachment from the host following feeding, and expression of OspD continues during tick digestion of the blood meal but is low or undetectable after the tick has molted. The high level of OspD production correlates to the highest cell densities that B. burgdorferi is known to reach in vivo. Although OspD is nonessential to the infectious cycle of B. burgdorferi, the tight regulation of expression suggests a beneficial contribution of OspD to the spirochete during bacterial replication within the tick midgut. PMID:18332210

  10. Quantification of Borrelia burgdorferi Membrane Proteins in Human Serum: A New Concept for Detection of Bacterial Infection.

    PubMed

    Cheung, Crystal S F; Anderson, Kyle W; Benitez, Kenia Y Villatoro; Soloski, Mark J; Aucott, John N; Phinney, Karen W; Turko, Illarion V

    2015-11-17

    The Borrelia burgdorferi spirochete is the causative agent of Lyme disease, the most common tick-borne disease in the United States. The low abundance of bacterial proteins in human serum during infection imposes a challenge for early proteomic detection of Lyme disease. To address this challenge, we propose to detect membrane proteins released from bacteria due to disruption of their plasma membrane triggered by the innate immune system. These membrane proteins can be separated from the bulk of serum proteins by high-speed centrifugation causing substantial sample enrichment prior to targeted protein quantification using multiple reaction monitoring mass spectrometry. This new approach was first applied to detection of B. burgdorferi membrane proteins supplemented in human serum. Our results indicated that detection of B. burgdorferi membrane proteins, which are ≈10(7) lower in abundance than major serum proteins, is feasible. Therefore, quantitative analysis was also carried out for serum samples from three patients with acute Lyme disease. We were able to demonstrate the detection of ospA, the major B. burgdorferi lipoprotein at the level of 4.0 fmol of ospA/mg of serum protein. The results confirm the concept and suggest that the proposed approach can be expanded to detect other bacterial infections in humans, particularly where existing diagnostics are unreliable. PMID:26491962

  11. Borrelia burgdorferi RevA Significantly Affects Pathogenicity and Host Response in the Mouse Model of Lyme Disease.

    PubMed

    Byram, Rebecca; Gaultney, Robert A; Floden, Angela M; Hellekson, Christopher; Stone, Brandee L; Bowman, Amy; Stevenson, Brian; Johnson, Barbara J B; Brissette, Catherine A

    2015-09-01

    The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, with increased fibrotic collagen deposition in tibiotarsal joints. The mutants also induced increased levels of the chemokine CCL2, a monocyte chemoattractant, in serum, and this increase was abolished in the complemented strain. Therefore, while revA is not absolutely essential for infection, deletion of revA had distinct effects on dissemination, arthritis severity, and host response.

  12. Interleukin-10 (IL-10) inhibits Borrelia burgdorferi-induced IL-17 production and attenuates IL-17-mediated Lyme arthritis.

    PubMed

    Hansen, Emily S; Medić, Velinka; Kuo, Joseph; Warner, Thomas F; Schell, Ronald F; Nardelli, Dean T

    2013-12-01

    Previous studies have shown that cells and cytokines associated with interleukin-17 (IL-17)-driven inflammation are involved in the arthritic response to Borrelia burgdorferi infection. Here, we report that IL-17 is a contributing factor in the development of Lyme arthritis and show that its production and histopathological effects are regulated by interleukin-10 (IL-10). Spleen cells obtained from B. burgdorferi-infected, "arthritis-resistant" wild-type C57BL/6 mice produced low levels of IL-17 following stimulation with the spirochete. In contrast, spleen cells obtained from infected, IL-10-deficient C57BL/6 mice produced a significant amount of IL-17 following stimulation with B. burgdorferi. These mice developed significant arthritis, including erosion of the bones in the ankle joints. We further show that treatment with antibody to IL-17 partially inhibited the significant hind paw swelling and histopathological changes observed in B. burgdorferi-infected, IL-10-deficient mice. Taken together, these findings provide additional evidence of a role for IL-17 in Lyme arthritis and reveal an additional regulatory target of IL-10 following borrelial infection.

  13. Control of immature Ixodes scapularis (Acari: Ixodidae) on rodent reservoirs of Borrelia burgdorferi in a residential community of southeastern Connecticut.

    PubMed

    Dolan, Marc C; Maupin, Gary O; Schneider, Bradley S; Denatale, Christopher; Hamon, Nick; Cole, Chuck; Zeidner, Nordin S; Stafford, Kirby C

    2004-11-01

    A 3-yr community-based study was conducted on residential properties on Mason's Island, Mystic, CT, to determine the efficacy of a rodent-targeted acaricide (fipronil) to control immature Ixodes scapularis (Say) on Peromyscus leucopus. Results indicated that modified commercial bait boxes were effective as an acaricide delivery method for reducing nymphal and larval tick infestations on white-footed mice by 68 and 84%, respectively. Passive application of fipronil significantly reduced the infection rate of Borrelia burgdorferi among white-footed mice by 53%. Moreover, the abundance of questing I. scapularis adults on treated properties was reduced by 77% and fewer were infected with spirochetes (31%) compared with untreated sites (47%) after 3 yr of treatment. Likewise, the abundance of host-seeking nymphs was significantly reduced on treated properties by >50%. Finally, infection rates in flagged nymphal ticks for both B. burgdorferi and Anaplasma phagocytophilum were reduced by 67 and 64%, respectively, after only 2 yr of treatment. Results from this 3-yr trial indicate that the use of fipronil passively applied to reservoir animals by bait boxes is an environmentally acceptable means to control ticks, interrupt the natural disease transmission cycle, and reduce the risk of Lyme disease for residents of treated properties.

  14. Bacteriolytic activity of selected vertebrate sera for Borrelia burgdorferi sensu stricto and Borrelia bissettii.

    PubMed

    Ullmann, Amy J; Lane, Robert S; Kurtenbach, Klaus; Miller, Michael; Schriefer, Martin E; Zeldner, Nordin; Piesman, Joseph

    2003-12-01

    An in vitro assay to evaluate the bacteriolytic activity of the complement pathway was applied to 2 strains of Borrelia bissettii, CO501 and DN127, and compared with that of B. burgdorferi sensu stricto B31. Sera from mule deer (Odocoileus hemionus) and the Western Fence lizard (Sceloporus occidentalis) were completely borreliacidal for B. burgdorferi and for both strains of B. bissettii. Serum from Bobwhite quail (Colinus virginianus) was nonlytic for B. burgdorferi and partially lytic for B. bissettii strains, CO-501 and DN127. Serum from a New Zealand White rabbit (Oryctolagus cuniculus) was partially lytic for all 3 strains of Borrelia, whereas serum from white-footed mice (Peromyscus leucopus) were nonlytic for all 3 Borrelia strains. The spectrum of complement sensitivity of B. bissettii appears to be similar to that of European B. afzelii in that tested rodent serum is not lytic to these 2 genospecies. Interestingly, both B. bissettii and B. afzelii have been found to be closely associated with rodents. Complement sensitivity demonstrated in these experiments may suggest and possibly predict specific reservoir-host associations. PMID:14740924

  15. Borrelia burgdorferi Stimulates Macrophages to Secrete Higher Levels of Cytokines and Chemokines than Borrelia afzelii or Borrelia garinii

    PubMed Central

    Strle, Klemen; Drouin, Elise E.; Shen, Shiqian; El Khoury, Joseph; McHugh, Gail; Ruzic-Sabljic, Eva; Strle, Franc; Steere, Allen C.

    2009-01-01

    To delineate the inflammatory potential of the 3 pathogenic species of Borrelia burgdorferi sensu lato, we stimulated monocyte-derived macrophages from healthy human donors with 10 isolates each of B. burgdorferi, B. afzelii, or B. garinii recovered from erythema migrans (EM) skin lesions of Lyme borreliosis patients from the United States or Slovenia. U.S. B. burgdorferi isolates induced macrophages to secrete significantly higher levels of IL-8, CCL3, CCL4, IL-6, IL-10 and TNF than B. garinii or B. afzelii isolates. Consistent with this response in cultured macrophages, the cytokine levels in sera of patients from whom the isolates were obtained were significantly greater in B. burgdorferi-infected patients than in B. afzelii- or B. garinii-infected patients. These results demonstrate in vitro and in vivo that B. burgdorferi has greater inflammatory potential than B. afzelii and B. garinii, which may account in part for variations in the clinical manifestations of Lyme borreliosis. PMID:19909078

  16. Spirochete from the Rabbit Tick, Haemaphysalis leporispalustris (Packard) I. Isolation and Preliminary Characterization

    PubMed Central

    Pickens, Edgar G.; Gerloff, Robert K.; Burgdorfer, Willy

    1968-01-01

    An unidentified spirochete, referred to as the 277F agent, was isolated from Haemaphysalis leporispalustris ticks from two cottontail rabbits by inoculation of the tick suspension into embryonated chicken eggs. Because of its minute width (0.1 μ), the organism was difficult to see when stained by the Giemsa method, but was readily demonstrated by silver impregnation or fluorescent-antibody procedures. In dark-field microscopy, the spirochetes appeared uniformly and rather tightly coiled, and exhibited typical corkscrewlike motility. After yolk-sac inoculation, the agent was highly lethal for chick embryos and was recovered in large quantity from several embryonic tissues and fluids. It could also be maintained in nonfertile eggs and in an enriched liquid medium. This previously undescribed spirochete could pass through Berkefeld N but not Seitz EK filters. It was relatively resistant to heat and to penicillin or sulfadiazine, but was markedly inhibited by streptomycin, broad-spectrum antibiotics, and homologous neutralizing antiserum. Of several species of animals tested for susceptibility to this spirochete, only the snowshoe hare gave evidence of infection. Images PMID:4171295

  17. Antigenic Targets of the Bovine Humoral Response to PDD-associated Spirochetes Change with Subsequent Exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Papillomatous digital dermatitis (PDD), also known as hairy heel wart, is a major cause of lameness of cows in the U.S. dairy industry. Cattle are known to mount a humoral response to spirochetes isolated from PDD lesions. This study was undertaken to evaluate the progression of the bovine humoral i...

  18. Papillomatous Digital Dermatitis Spirochetes Suppress the Bovine Macrophage Innate Immune Response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Papillomatous digital dermatitis (PDD) is a polymicrobial infection in soft tissue adjacent to the hoof and is the leading cause of lameness in dairy cattle. Treponema phagedenis-like (TPL) spirochetes are a constant feature of PDD lesions and are localized deep in infected tissue. Host-cell respon...

  19. Colorado tick fever

    MedlinePlus

    ... immediately by using tweezers, pulling carefully and steadily. Insect repellent may be helpful