Borrelia burgdorferi genes selectively expressed in the infected host.

Suk, Kyoungho; Das, Subrata; Sun, Weijian; Jwang, Biru; Barthold, Stephen W.; Flavell, Richard A.; Fikrig, Erol

doi:10.1073/pnas.92.10.4269

Cited by 164 publications

(186 citation statements)

References 13 publications

(4 reference statements)

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“…It is quite likely that the patients who lacked an immune response were infected with a B. burgdorferi strain that did not produce proteins closely related to OspE, OspF, or pG. Additionally, Suk et al (50) discriminated between antibodies directed against the OspE and p21 proteins of B. burgdorferi N40 by using an 11-amino-acid polypeptide found only in p21. This amino acid sequence is not found in any of the B. burgdorferi B31 Erp proteins, which raises doubts as to whether it would be useful in screening sera from patients with Lyme disease.…”

Section: Discussionmentioning

confidence: 99%

“…Such rearrangements may serve to prevent the bacteria from being immediately recognized and cleared by the immune systems of previously infected mammals. Several reports indicate that at least some of the OspEF-related proteins are antigenic in infected humans and laboratory animals (1,26,32,(49)(50)(51). The pres- ence within a single bacterium of a number of different genes encoding OspEF-related proteins may also allow sequential expression of the proteins during the course of mammalian infection.…”

Section: Discussionmentioning

confidence: 99%

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A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31

1996

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We have identified four loci in Borrelia burgdorferi B31 that contain open reading frames capable of encoding six proteins that are related to the antigenic proteins OspE and OspF. We have designated these proteins Erp, for OspEF-related protein, and named their respective genes erp. The erpA and erpB genes are linked, as are erpC and erpD, and the pairs probably constitute two operons. The erpG and erpH genes appear to be monocistronic. The ErpA and ErpC proteins are expressed by B. burgdorferi B31 in culture and are recognized by a polyclonal antiserum raised against the OspE protein of B. burgdorferi N40. The four erp loci are each located on different 32-kb circular plasmids that contain additional DNA sequences that are homologous to each other and to an 8.3-kb circular plasmid of B. burgdorferi sensu lato Ip21. All four 32-kb plasmids can be maintained within a single bacterium, which may provide a model for the study of plasmid replication and segregation in B. burgdorferi.Borrelia burgdorferi is a member of the order Spirochaetales, the spirochetes, an order that is phylogenetically and morphologically distinct from such well-characterized bacteria as Escherichia coli and Bacillus subtilis (8,24,34,35,53). B. burgdorferi bacteria naturally contain a wide variety of plasmids (4,13,25,40,42,45,47,54), yet nothing is known about the mechanisms by which plasmids are maintained in these bacteria. Several observations suggest that the small DNA species of B. burgdorferi and other spirochetes may be fundamentally different from the plasmids of other bacteria, the most significant being that there are linear plasmids in B. burgdorferi (4,5,7,13,22,23,42). Also, two B. burgdorferi genes involved in purine biosynthesis are located on a circular plasmid (29), which appears to be inconsistent with the classical definition of a plasmid as a nonessential extrachromosomal element. Other plasmids of B. burgdorferi appear to be capable of undergoing recombination to form multimeric plasmids (25, 31), and there have been reports of DNA sequences located on several different plasmids within the same bacterium (46,47,(54)(55)(56).B. burgdorferi is the causative agent of Lyme disease, an increasingly common ailment of humans and several other mammals (15,48). Infection of a mammal by B. burgdorferi is generally accompanied by the production of antibodies directed against a limited number of bacterial antigens (17,19,41,52), several of which have been identified as surface-exposed lipoproteins. At least three of these lipoproteins, OspC, OspE, and OspF, are differentially expressed by B. burgdorferi, being produced in greater quantities by cultured bacteria that are shifted from 23 to 32ЊC than by those maintained at the lower temperature (43, 49). For OspC, at least, this appears to be related to induction of specific protein synthesis by the spirochete in ticks following feeding upon a warm-blooded animal (43). Temperature-dependent differential expression of bacterial proteins that are involved in host infection has been o...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31

1996

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“…Transcripts from erp genes have been detected in various tissues of infected laboratory animals, including non-human primates, throughout the course of disseminated and persistent infection . B. burgdorferi-infected mice mount rapid antibody responses to Erp proteins Akins et al, 1995;Suk et al, 1995;Wallich et al, 1995;Stevenson et al, 1998;Miller et al, 2000b;Hefty et al, 2001Hefty et al, , 2002McDowell et al, 2001). Erp-directed antibodies persist at high levels and periodically increase during prolonged infection, suggesting sustained exposure (and re-exposure) to Erp proteins throughout chronic infection .…”

Section: Disseminated Mammalian Infectionmentioning

confidence: 99%

Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal–tick infection cycle

Bykowski

Woodman

Cooley

et al. 2008

International Journal of Medical Microbiology

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Host complement is widely distributed throughout mammalian body fluids and can be activated immediately as part of the first line of defense against invading pathogens. The agent of Lyme disease, Borrelia burgdorferi sensu lato (s.l.), is naturally resistant to that innate immune defense system of its hosts. One resistance mechanism appears to involve binding fluid-phase regulators of complement to distinct borrelial outer surface molecules known as CRASPs (complement regulator acquiring surface proteins). Using sensitive molecular biology techniques, expression patterns of all three classes of genes encoding the CRASPs of B. burgdorferi sensu stricto (BbCRASPs) have been analyzed throughout the natural tick-mammal infection cycle. Each class shows a different expression profile in vivo and the results are summarized herein. Studies on the expression of B. burgdorferi genes using animal models of infection have advanced our knowledge on the ability of the causative agent to circumvent innate immune defenses, the contributions of CRASPs to spirochete infectivity, and the pathogenesis of Lyme disease.

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“…Yet another group of B. burgdorferi genes, e.g. eppA, pG, p21, bbK2.10, and p35, seem to be selectively expressed in the mammalian environment, at least temporarily [1,2,10,14,15,59,60].…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Lederer

Brenner

Stehlé

et al. 2004

Med Microbiol Immunol

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Adaptation of Borrelia burgdorferi in the vector and vertebrate host is mediated by mechanisms that regulate differential expression of outer surface lipoproteins (Osps). In this study, real time PCR was applied to quantify tissue-specific expression of four linear plasmid (lp54)-encoded (ospA, zs7.a36, zs7.a66 zs7.a68) and one circular plasmid (cp26)-encoded (ospC) gene from B. burgdorferi sensu stricto, in a natural setting of tick-infected immunodeficient (C.B-17 SCID) and immunocompetent (BALB/c and AKR/OlaHsd) mice for up to 120 days post-infection (p.i.). Early during infection (day 30 p.i.) high numbers of spirochetes were found in the heart and joint, but not the ear and spleen tissues of disease-susceptible SCID mice. In diseasesusceptible AKR mice spirochetes colonized the ear and joint tissues, but were undetectable in tissues of diseaseresistant BALB/c mice. Later in infection (day 120 p.i.), spirochetes had expanded ($1,000-fold) in all SCID tissues tested but were undetectable in AKR and BALB/ c mice. Of the five genes analyzed, only zs7.a36 transcripts were detected in various tissues of all infected mouse strains, though at differing levels, whereas ospC transcripts were only found in tissue specimens of SCID mice. Furthermore, gene expression of ospC and zs7.a36 appears to be differentially regulated in distinct organs of individual mice. In contrast, transcripts for ospA, zs7.a66, and zs7.a68 were not detected in any of the mouse strains, independent of their immune status and/ or the severity of their infection/inflammatory responses. Late during infection (day 120 p.i.), transcription of zs7.a36 and ospC was down-regulated in the tissues of SCID mice despite expansion of spirochetes. This type of quantitative analysis may be helpful to further disclose principles of pathogenesis of Lyme borreliosis and to design strategies for its therapeutic treatment.

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Borrelia burgdorferi genes selectively expressed in the infected host.

Abstract: An immunological screening strategy was used to select microbial genes expressed only in the host.

Cited by 164 publications

References 13 publications

A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31

A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31

Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal–tick infection cycle

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

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