title: Inadequate binding of immune regulator factor H is associated with sensitivity of Borrelia lusitaniae to human complement.
abstract: Spirochetes belonging to the Borrelia burgdorferi sensu lato complex differ in resistance to complement-mediated killing by human serum. Here, we characterize complement sensitivity of a panel of B. lusitaniae isolates derived from ticks collected in Germany and Portugal as well as one patient-derived isolate, PoHL. All isolates are highly susceptible to complement-mediated lysis in human serum and activate complement predominantly by the alternative pathway, leading to an increased deposition of complement components C3, C6, and the terminal complement complex. Interestingly, serum-sensitive B. lusitaniae isolates were able to bind immune regulator factor H (CFH), and some strains also bound CFH-related protein 1 (CFHR1) and CFHR2. Moreover, CFH bound to the surface of B. lusitaniae was inefficient in mediating C3b conversion. Furthermore, the identification and characterization of a potential CFH-binding protein, OspE, revealed that this molecule possesses a significantly reduced binding capacity for CFH compared to that of CFH-binding OspE paralogs expressed by various serum-resistant Borrelia species. This finding suggests that a reduced binding capability of CFH is associated with an increased serum sensitivity of B. lusitaniae to human complement.
authors.affiliation: Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Dieterich
authors.forename: Claudia
authors.initials: C
authors.lastname: Hammerschmidt
authors.forename: Dania
authors.initials: D
authors.lastname: Richter
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wallich
authors.forename: Franz-Rainer
authors.initials: FR
authors.lastname: Matuschka
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Peter
authors.initials: P
authors.lastname: Kraiczy
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001770:Blood Bactericidal Activity; D001798:Blood Proteins; D001898:Borrelia / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001899:Borrelia Infections / Q000276:immunology* / Q000382:microbiology; D003167:Complement Activation / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000737:chemistry / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000276:immunology*; D005858:Germany; D006801:Humans; D018884:Ixodes / Q000382:microbiology; D008969:Molecular Sequence Data; D011174:Portugal; D017422:Sequence Analysis, DNA
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001798:Blood Proteins; C517621:CFHR1 protein, human; C586681:CFHR2 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H
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