Four clones of Borrelia burgdorferi sensu stricto cause invasive infectionin humans

Lyme disease begins at the site of a tick bite, producing a primary infecti on with spread of the organism to secondary sites occurring early in the co urse of infection. A major outer surface protein expressed by the spirochet e early in infection is outer surface protein C (OspC). In Borrelia burgdor feri sensu stricto, OspC is highly variable. Based on sequence divergence, alleles of ospC can be divided into 21 major groups. To assess whether stra in differences defined by ospC group are linked to invasiveness and pathoge nicity, we compared the frequency distributions of major ospC groups from t icks, from the primary erythema migrans skin lesion, and from secondary sit es, principally from blood and spinal fluid. The frequency distribution of ospC groups from ticks is significantly different from that from primary si tes, which in turn is significantly different from that from secondary site s. The major groups A, B, I, and K had higher frequencies in the primary si tes than in ticks and were the only groups found in secondary sites. We def ine 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 i nfection at the tick bite site, and a third that causes systemic disease. T he finding that all systemic B. burgdorferi sensu stricto infections are as sociated with four ospC groups has importance in the diagnosis, treatment, and prevention of Lyme disease.