Lyme Disease Microbiology - Outer Surface Proteins

Outer Surface Proteins

The outer membrane of Borrelia burgdorferi is composed of various unique outer surface proteins (Osp) that have been characterized (OspA through OspF). The Osp proteins are lipoproteins anchored by N-terminally-attached fatty acid molecules to the membrane. They are presumed to play a role in virulence, transmission, or survival in the tick.

OspA, OspB, and OspD are expressed by B. burgdorferi residing in the gut of unfed ticks, suggesting they promote the persistence of the spirochete in ticks between blood meals. During transmission to the mammalian host, when the nymphal tick begins to feed and the spirochetes in the midgut begin to multiply rapidly, most spirochetes cease expressing OspA on their surfaces. Simultaneous with the disappearance of OspA, the spirochete population in the midgut begins to express an OspC and migrate to the salivary gland. Upregulation of OspC begins during the first day of feeding and peaks 48 hours after attachment.

The OspA and OspB genes encode the major outer membrane proteins of the B. burgdorferi. The two Osp proteins show a high degree of sequence similarity, indicating a recent duplication event. Virtually all spirochetes in the midgut of an unfed nymph tick express OspA. OspA promotes the attachment of B. burgdorferi to the tick protein TROSPA, present on tick gut epithelial cells. OspB also has an essential role in the adherence of B. burgdorferi to the tick gut. Although OspD has been shown to bind to tick gut extracts in vitro, as well as OspA and OspB, it is not essential for the attachment and colonization of the tick gut, and it is not required for human infections.

OspC is a strong antigen; detection of its presence by the host organism stimulates an immune response. While each individual bacterial cell contains just one copy of the ospC gene, the gene sequence of ospC among different strains within each of the three major Lyme disease species is highly variable. OspC plays an essential role during the early stage of mammalian infection. In infected ticks feeding on a mammalian host, OspC may also be necessary to allow B. burgdorferi to invade and attach to the salivary gland after leaving the gut, although not all studies agree on such a role for the protein. OspC attaches to the tick salivary protein Salp15, which protects the spirochete from complement and impairs the function of dendritic cells.

OspE and OspF were initially identified in B. burgdorferi strain N40. The ospE and ospF genes are structurally arranged in tandem as one transcriptional unit under the control of a common promoter. It is now known that individual strains of B. burgdorferi carry multiple related copies of the ospEF locus, which are now collectively referred to as erp (OspE/F-like related protein). In B. burgdoreri strains B31 and 297, most of the erp loci occupy the same position on the multiple copies of the cp32 plasmid present in these strains. Each erp locus consists of one or two erp genes. When two genes are present, they are transcribed as one operon, although in some cases, an internal promoter in the first gene may also transcribe the second gene. The presence of multiple Erp proteins was proposed to be important in allowing B. burgdorferi to evade killing by the alternative complement pathway of a broad range of potential animal hosts, as individual Erp proteins exhibited different binding patterns to the complement regulator factor H from different animals. However, the presence of factor H was recently demonstrated to not be necessary to enable B. burgdorferi to infect mice, suggesting the Erp proteins have an additional function.