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 theIxodesspp. 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 facilitatesB. burgdorferiinfection in the mammalian host. The deletion ofbba33eliminatedB. burgdorferiinfectivity in C3H mice, which was rescued by genetic complementation with intactbba33. With regard to function, a combinatorial peptide approach, coupled with subsequentin vitrobinding 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.
Borrelia burgdorferi, the etiologic agent of Lyme disease, binds to extracellular matrix targets, including collagen. Despite this connection, there are no borrelial proteins known to specifically mediate this interaction. In the Zhi et al. report, the surface exposed BBA33 lipoprotein is shown to bind to collagen type VI, and to a lesser extent, type IV. The absence of bba33 greatly impairs borrelial infectivity, providing a link to collagen adherence and B. burgdorferi pathogenesis.