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Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity.

Grosskinsky S, Schott M, Brenner C, Cutler SJ, Kraiczy P, Zipfel PF, Simon MM, Wallich R - PLoS ONE (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Infectious Immunology, Institute for Immunology, University of Heidelberg, Heidelberg, Germany.

ABSTRACT
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.

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HcpA exhibits 54% amino acid sequence similarity to BhCRASP of B. hermsii HS1.
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pone-0004858-g002: HcpA exhibits 54% amino acid sequence similarity to BhCRASP of B. hermsii HS1.

Mentions: To isolate and further characterize HcpA, whole cell lysates of B. recurrentis A1 were incubated with CFH and subsequently treated with a goat anti-CFH immune serum. A resulting co-precipitated protein of 17 kDa was analyzed by mass spectrometry and peptides generated matched an open reading frame of 525 bp on the genome of B. recurrentis A1 (unpublished data), designated hcpA. Due to the presence of a spirochetal lipobox at its N-terminus HcpA represents a putative outer surface lipoprotein [33]. The deduced amino acid sequence exhibits 54% similarity with the recently identified BhCRASP-1 of B. hermsii HS1 (Fig. 2) [8]. A BLAST search detected another protein with significant homology in the genome of B. turicatae, indicating that this protein is to be found in other Borrelia species. To further elucidate the binding properties of HcpA for complement regulators CFH and CFHR-1, various N- and C-terminal deletion mutants of HcpA were generated. Variants of the encoding hcpA gene lacking the hydrophobic leader peptide and the indicated N- or C-terminal regions were cloned and expressed as His-tagged fusion proteins in E. coli (Fig. 3). Expression of each protein was confirmed by immunoblot analysis using anti-His antiserum (Fig. 3A).


Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity.

Grosskinsky S, Schott M, Brenner C, Cutler SJ, Kraiczy P, Zipfel PF, Simon MM, Wallich R - PLoS ONE (2009)

HcpA exhibits 54% amino acid sequence similarity to BhCRASP of B. hermsii HS1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654920&req=5

pone-0004858-g002: HcpA exhibits 54% amino acid sequence similarity to BhCRASP of B. hermsii HS1.
Mentions: To isolate and further characterize HcpA, whole cell lysates of B. recurrentis A1 were incubated with CFH and subsequently treated with a goat anti-CFH immune serum. A resulting co-precipitated protein of 17 kDa was analyzed by mass spectrometry and peptides generated matched an open reading frame of 525 bp on the genome of B. recurrentis A1 (unpublished data), designated hcpA. Due to the presence of a spirochetal lipobox at its N-terminus HcpA represents a putative outer surface lipoprotein [33]. The deduced amino acid sequence exhibits 54% similarity with the recently identified BhCRASP-1 of B. hermsii HS1 (Fig. 2) [8]. A BLAST search detected another protein with significant homology in the genome of B. turicatae, indicating that this protein is to be found in other Borrelia species. To further elucidate the binding properties of HcpA for complement regulators CFH and CFHR-1, various N- and C-terminal deletion mutants of HcpA were generated. Variants of the encoding hcpA gene lacking the hydrophobic leader peptide and the indicated N- or C-terminal regions were cloned and expressed as His-tagged fusion proteins in E. coli (Fig. 3). Expression of each protein was confirmed by immunoblot analysis using anti-His antiserum (Fig. 3A).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Infectious Immunology, Institute for Immunology, University of Heidelberg, Heidelberg, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus