Differential binding of host complement inhibitor factor H by Borrelia burgdorferi Erp surface proteins: a possible mechanism underlying the expansive host range of Lyme disease spirochetes

Abstract

The Lyme disease spirochete, Borrelia burgdorferi, is capable of infecting a wide variety of vertebrates. This broad host range implies that B. burgdorferi possesses the ability to contravene the immune defenses of many potential hosts. B. burgdorferi produces multiple different Erp proteins on its outer membrane during mammalian infection. It was reported previously that one Erp protein can bind human factor H (J. Hellwage, T. Meri, T. Heikkilä, A. Alitalo, J. Panelius, P. Lahdenne, I. J. T. Seppälä, and S. Meri, J. Biol. Chem. 276:8427-8435, 2001). In this paper we report that the ability to bind the complement inhibitor factor H is a general characteristic of Erp proteins. Furthermore, each Erp protein exhibits different relative affinities for the complement inhibitors of various potential animal hosts. The data suggest that the presence of multiple Erp proteins on the surface can allow a single B. burgdorferi bacterium to resist complement-mediated killing in any of the wide range of potential hosts that it might infect. Thus, Erp proteins likely contribute to the persistence of B. burgdorferi in nature and to the ability of this bacterium to cause Lyme disease in humans and other animals.

FIG. 1.

Immunoaffinity blot analyses of recombinant Erp proteins performed with either purified human factor H or whole human serum. Some purified recombinant protein preparations contain multimers or breakdown products (68). The lanes contained different Erp proteins, as indicated at the top. The positions of molecular mass markers (in kilodaltons) are indicated on the left.

FIG. 2.

Immunoblot analysis of animal serum samples performed with goat anti-human factor H polyclonal antiserum. Human factor H has a molecular mass of 155 kDa, and FHL-1 has a molecular mass of 42 kDa (26, 78). The positions of molecular mass markers (in kilodaltons) are indicated on the left.

FIG. 3.

Immunoaffinity blot analyses of recombinant Erp proteins performed with whole sera from various animals. Some purified recombinant protein preparations contain multimers or breakdown products (68). The lanes contained different Erp proteins, as indicated at the top. The positions of molecular mass markers (in kilodaltons) are indicated on the left.

FIG. 4.

Diagram of the life cycles of B. burgdorferi and Ixodes sp. vector ticks. Tick larvae hatch and feed once; then they molt into nymphs, which also feed once, and then into adults, which mate, feed once, lay eggs, and then die (dashed arrows). Larvae acquire B. burgdorferi by feeding on infected hosts and then transmit the bacteria to new hosts during feeding in the nymph and adult stages (solid arrows). The tick hosts include a large variety of species of mammals, birds, and reptiles, many of which are susceptible to B. burgdorferi infection and serve as reservoir animals. In many geographic areas, adult Ixodes sp. ticks do not feed on the same animal hosts as the larvae or nymphs and so do not contribute greatly to the maintenance of B. burgdorferi in these locations (35, 67).