Genetic analysis of Borrelia garinii OspA serotype 4 strains associated with neuroborreliosis: Evidence for extensive genetic homogeneity

Infection with Borrelia garinii outer surface protein (Osp) A serotype 4 st rains has been correlated with the development of neuroborreliosis in Lyme borreliosis patients in Europe. OspA serotype 4 isolates have been recovere d primarily from human cerebrospinal fluid, suggesting a tropism for this e nvironment. Previous studies with monoclonal antibodies directed against Os pA and OspC demonstrated that OspA serotype 4 strains are antigenically clo sely related. In view of the pronounced antigenic and genetic variability t hat has been noted in the Osps of other Borrelia isolates, we sought to det ermine if OspA serotype 4 strains represent a recently emerged clonal linea ge of B. garinii, Toward this goal, a representative group of OspA serotype 4 strains was analyzed for traits that typically exhibit hypervariability among isolates that cause Lyme borreliosis. The following criteria were ass essed: (i) ospC sequences, (ii) plasmid composition, (iii) genomic restrict ion fragment length polymorphism (RFLP) patterns, and (iv) the RFLP pattern s of the upstream homology box (UHB) element which flanks members of the UH B gene family at their 5' end. Collectively, these analyses demonstrate gen etic homogeneity, suggesting that OspA serotype 4 strains are a recently em erged clonal lineage with an apparent tropism for the central nervous syste m.