Dissociation of Infectivity and Pathogenicity in
            <i>Borrelia burgdorferi</i>

Thomas, Venetta; Anguíta, Juan; Samanta, Swapna; Rosa, Patricia A.; Stewart, Philip E.; Barthold, Stephen W.; Fikrig, Erol

doi:10.1128/iai.69.5.3507-3509.2001

Cited by 20 publications

(16 citation statements)

References 34 publications

(29 reference statements)

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“…Erps and CRASP-1 interact with complement regulatory proteins such as factor H and factor H-like protein 1, and are encoded on the cp32 family of plasmids and lp54, respectively (12,20). To evade adaptive immunity, B. burgdorferi dramatically up-regulates immune evasion genes such as vlsE (13,39,65), consistent with the well-defined role of lp28-1, which carries the gene, in the establishment of chronic infection in immunocompetent mice (32,48,59,65). In addition, ligandbinding lipoproteins such as decorin-binding proteins A and B, encoded on lp54, and fibronectin-binding protein, carried by lp36, may help the spirochete colonize the host tissues and establish chronic infection in the immune environment (9,23,35,46).…”

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confidence: 76%

Association of Linear Plasmid 28-1 with an Arthritic Phenotype ofBorrelia burgdorferi

Seemanapalli

Lomax

et al. 2005

Infect Immun

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Borrelia burgdorferi, the Lyme disease spirochete, has a genome comprised of a linear chromosome and up to 21 plasmids. Loss of plasmids is associated with decreased infectivity and pathogenicity. Sixteen transformants were generated by transforming the noninfectious clone 5A13 with the recombinant plasmid pBBE22. The transformants were classified into nine groups based on plasmid content analysis. An infectivity study revealed that all nine transformants examined, each of which represented one of the plasmid patterns, were infectious in mice with severe combined immunodeficiency (SCID) regardless of their genomic compositions. Tissue bacterial quantification revealed that the loss of plasmids significantly reduced the spirochete burden in the heart and joint tissues, not in the skin, suggesting virulence factors may be tissue specific. Four transformants containing lp28-1 induced severe arthritis in SCID mice, in contrast to the five transformants lacking lp28-1. These pathogenicity studies associated lp28-1 with an arthritic phenotype and further studies may identify factors that contribute to arthritic pathology.

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confidence: 76%

Association of Linear Plasmid 28-1 with an Arthritic Phenotype ofBorrelia burgdorferi

Seemanapalli

Lomax

et al. 2005

Infect Immun

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“…B. burgdorferi has an unusual genome consisting of a linear chromosome of 910 kb and 21 plasmids (12 linear and 9 circular) giving an additional 611 kb (Casjens et al, 2000;Fraser et al, 1997). Previous studies have shown that several B. burgdorferi plasmids are important for infectivity (Hefty et al, 2002;Purser et al, 2003;Purser & Norris, 2000;Schwan et al, 1988a;Thomas et al, 2001). Culture passages of B. burgdorferi are associated with loss of plasmids (Barbour, 1988) and thereby loss of infectivity Schwan et al, 1988a;Xu et al, 1996).…”

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confidence: 99%

Molecular analysis of the channel-forming protein P13 and its paralogue family 48 from different Lyme disease Borrelia species

et al. 2004

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The aetiological agent of Lyme disease, Borrelia burgdorferi cycles between its tick vector and mammalian hosts, implying that it can sense different environments and consequently change the expression of genes encoding several surface-associated proteins. The genome of the type strain B. burgdorferi B31 has revealed 175 different gene families. The p13 gene, situated on the chromosome, encodes a channel-forming protein that belongs to the gene family 48 consisting of eight additional paralogous genes. The heterogeneity of the P13 protein from different Lyme disease Borrelia strains was investigated. The predicted surface-exposed domains are the most heterogeneous regions and contain probable epitopes of P13. The membrane-spanning architecture of P13 was determined and a model for the location of this protein in the outer membrane is presented. The transcription of the paralogues of gene family 48 during in vitro culturing and in a mouse infection model was also analysed. The bba01 gene is the only p13 paralogue present in all three Lyme-disease-causing genospecies; it is stable during cultivation in vitro and the BBA01 protein was expressed in all Borrelia strains investigated. Conversely, paralogues bbi31, bbq06 and bbh41 were only detected in B. burgdorferi and the corresponding plasmids harbouring bbi31 and bbh41 were lost during in vitro passage. Finally, p13 and bbi31 are the only members of gene family 48 that are transcribed in mice, suggesting their importance during mammalian infection.

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“…More recently, lp28-1 and lp25 have been associated with the infectivity of B. burgdorferi B31 (19,20). Noninfectious B. burgdorferi N40 that have been passaged 120 times in vitro (B. burgdorferi N40-120) lack both lp28-1 and lp38 (21). The factors that contribute to spirochete infectivity and the pathogenesis of Lyme disease are thus clearly multifactorial, involving close interactions between B. burgdorferi and the host.…”

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Borrelia burgdorferi-Induced Inflammation Facilitates Spirochete Adaptation and Variable Major Protein-Like Sequence Locus Recombination

Anguíta

Thomas

Samanta

et al. 2001

The Journal of Immunology

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Spirochete adaptation in vivo is associated with preferential Borrelia burgdorferi gene expression. In this paper, we show that the administration of B. burgdorferi-immune sera to IFN-γR-deficient mice that have been infected with B. burgdorferi N40 for 4 days causes spirochete clearance. In contrast, immune sera-mediated clearance of B. burgdorferi N40 is not apparent in immunocompetent mice, suggesting a role for IFN-γ-mediated responses in B. burgdorferi N40 host adaptation. B. burgdorferi-immune sera also induces clearance of B. burgdorferi N40 that have been passaged in vitro 75 times (B. burgdorferi N40-75), a derivative of B. burgdorferi N40 that does not rapidly adapt in vivo in immunocompetent mice. B. burgdorferi N40-75 produce lower levels of IFN-γ and IL-12 in mice than does B. burgdorferi N40, and the administration of these cytokines to B. burgdorferi N40-75-infected mice results in an increased spirochetal burden, further indicating that IFN-γ-mediated events promote B. burgdorferi survival. Differential immunoscreening and RT-PCR demonstrate that IFN-γ-mediated signals facilitate spirochete recombination at the variable major protein like sequence locus, a site for early antigenic variation in vivo, and that recombination rates by B. burgdorferi N40 are lower in IFN-γR-deficient mice than in control animals. These results suggest that the murine immune response can promote the in vivo adaptation of B. burgdorferi.

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Dissociation of Infectivity and Pathogenicity in Borrelia burgdorferi

Cited by 20 publications

References 34 publications

Association of Linear Plasmid 28-1 with an Arthritic Phenotype ofBorrelia burgdorferi

Association of Linear Plasmid 28-1 with an Arthritic Phenotype ofBorrelia burgdorferi

Molecular analysis of the channel-forming protein P13 and its paralogue family 48 from different Lyme disease Borrelia species

Borrelia burgdorferi-Induced Inflammation Facilitates Spirochete Adaptation and Variable Major Protein-Like Sequence Locus Recombination

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