title: The BBA33 lipoprotein binds collagen and impacts Borrelia burgdorferi pathogenesis.
abstract: Borrelia burgdorferi, the etiologic agent of Lyme disease, adapts to the mammalian hosts by differentially expressing several genes in the BosR and Rrp2-RpoN-RpoS dependent pathways, resulting in a distinct protein profile relative to that seen for survival in the Ixodes spp. tick. Previous studies indicate that a putative lipoprotein, BBA33, is produced in an RpoS-dependent manner under conditions that mimic the mammalian component of the borrelial lifecycle. However, the significance and function for BBA33 is not known. Given its linkage to the BosR/Rrp2-RpoN-RpoS regulatory cascade, we hypothesized that BBA33 facilitates B. burgdorferi infection in the mammalian host. The deletion of bba33 eliminated B. burgdorferi infectivity in C3H mice, which was rescued by genetic complementation with intact bba33. With regard to function, a combinatorial peptide approach, coupled with subsequent in vitro binding assays, indicated that BBA33 binds to collagen type VI and, to a lesser extent, collagen type IV. Whole cell binding assays demonstrated BBA33-dependent binding to human collagen type VI. Taken together, these results suggest that BBA33 interacts with collagenous structures and may function as an adhesin in a process that is required to prevent bacterial clearance.
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, Bryan, TX, 77807, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhi
authors.forename: Eric H
authors.initials: EH
authors.lastname: Weening
authors.forename: Elena Magda
authors.initials: EM
authors.lastname: Barbu
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Hyde
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.forename: Jon T
authors.initials: JT
authors.lastname: Skare
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D003094:Collagen / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D011485:Protein Binding
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D008074:Lipoproteins; D003094:Collagen