Four Clones of Borrelia burgdorferi Sensu Stricto Cause Invasive Infection in Humans

Abstract

Lyme disease begins at the site of a tick bite, producing a primary infection with spread of the organism to secondary sites occurring early in the course of infection. A major outer surface protein expressed by the spirochete early in infection is outer surface protein C (OspC). In Borrelia burgdorferi sensu stricto, OspC is highly variable. Based on sequence divergence, alleles ofospC can be divided into 21 major groups. To assess whether strain differences defined by ospC group are linked to invasiveness and pathogenicity, we compared the frequency distributions of major ospC groups from ticks, from the primary erythema migrans skin lesion, and from secondary sites, principally from blood and spinal fluid. The frequency distribution of ospC groups from ticks is significantly different from that from primary sites, which in turn is significantly different from that from secondary sites. The major groups A, B, I, and K had higher frequencies in the primary sites than in ticks and were the only groups found in secondary sites. We define three categories of major ospC groups: one that is common in ticks but very rarely if ever causes human disease, a second that causes only local infection at the tick bite site, and a third that causes systemic disease. The finding that all systemicB. burgdorferi sensu stricto infections are associated with four ospC groups has importance in the diagnosis, treatment, and prevention of Lyme disease.

Borrelia burgdorferiouter surface protein C (OspC) binds complement component C4b and confers bloodstream survival

“…OspC displays high variability of the central region of the OspC protein among not only different species of Lyme disease Borrelia but also between different strains within the same species (Lin, Oliver, & Gao, 2002), limiting the cross-protective activity of vaccines based on OspC (Probert, Crawford, Cadiz, & LeFebvre, 1997). Based on this variability, OspC from different strains and species of Lyme disease Borrelia have been separated into 22 different classes (named A-U) with alleles having less than 2% variability in nucleotide sequence falling into the same class, and different classes of alleles having greater than 8% sequence variability between them (Earnhart, Buckles, Dumler, & Marconi, 2005;Seinost et al, 1999). Strains that produce class A, B, C, D, I, K, or N have been associated with disseminated infection in humans or mice (Earnhart et al, 2005;Lagal, Postic, Ruzic-Sabljic, & Baranton, 2003;Seinost et al, 1999;Wang et al, 2001;Wang et al, 2002).…”

“…Based on this variability, OspC from different strains and species of Lyme disease Borrelia have been separated into 22 different classes (named A-U) with alleles having less than 2% variability in nucleotide sequence falling into the same class, and different classes of alleles having greater than 8% sequence variability between them (Earnhart, Buckles, Dumler, & Marconi, 2005;Seinost et al, 1999). Strains that produce class A, B, C, D, I, K, or N have been associated with disseminated infection in humans or mice (Earnhart et al, 2005;Lagal, Postic, Ruzic-Sabljic, & Baranton, 2003;Seinost et al, 1999;Wang et al, 2001;Wang et al, 2002). Due to the differences in invasiveness and disease seen with Borrelia carrying the various OspC classes, and its requirement for B. burgdorferi survival early in infection, it is possible that OspC may be an effector for evasion of innate defences in the host.…”

The long strange trip of Borrelia burgdorferi outer‐surface protein C

“…Crystallographic analysis did, on the other hand, provide tantalizing indirect evidence linking OspC to spirochetal dissemination. Seinost et al (1999) had shown that only a few of the numerous ospC alleles circulating among spirochaetes in ticks appear to be associated with disseminated borrelial infection of humans. Kumaran et al (2001) found that OspCs from invasive clones have a much greater electrostatic potential at their distal ends, which they proposed enhances binding to positively charged extracellular matrix components.…”

Solving a sticky problem: new genetic approaches to host cell adhesion by the Lyme disease spirochete

“…These bacteria are highly motile, and spread through the dermis, causing a characteristic expanding 'bulls eye' rash in humans termed erythema migrans. Some B. burgdorferi strains, which have been classified by their ospC alleles (Seinost et al ., 1999) or other polymorphisms (Wormser et al ., 1999), are apparently capable of causing only local skin infection in humans and do not discernibly spread to other tissues. Other strains, in the days and weeks following initial infection, spread to sites such as the heart, joints, nervous tissue, or distant locations in the skin.…”

“…The specific defect underlying this loss of infectivity is not known, but several observations make OspC an attractive candidate adhesin for mammalian cell attachment. It is produced early in mammalian infection (Schwan et al, 1995), is highly polymorphic (Jauris-Heipke et al, 1993;Stevenson and Barthold, 1994;Wang et al, 1999), and only a subset of ospC alleles is associated with invasive disease and/or successful colonization of particular enzootic hosts (Luft et al, 1989;Seinost et al, 1999;Wormser et al, 1999;Brisson and Dykhuizen, 2004). Furthermore, unpublished experiments suggest that several recombinant OspC alleles also bind to GAGs or fibronectin (N. Parveen, unpub.…”