title: Imbalanced presence of Borrelia burgdorferi s.l. multilocus sequence types in clinical manifestations of Lyme borreliosis.
abstract: In this study we used typing based on the eight multilocus sequence typing scheme housekeeping genes (MLST) and 5S-23S rDNA intergenic spacer (IGS) to explore the population structure of Borrelia burgdorferi sensu lato isolates from patients with Lyme borreliosis (LB) and to test the association between the B. burgdorferi s.l. sequence types (ST) and the clinical manifestations they cause in humans. Isolates of B. burgdorferi from 183 LB cases across Europe, with distinct clinical manifestations, and 257 Ixodes ricinus lysates from The Netherlands, were analyzed for this study alone. For completeness, we incorporated in our analysis also 335 European B. burgdorferi s.l. MLST profiles retrieved from literature. Borrelia afzelii and Borrelia bavariensis were associated with human cases of LB while Borrelia garinii, Borrelia lusitaniae and Borrelia valaisiana were associated with questing I. ricinus ticks. B. afzelii was associated with acrodermatitis chronica atrophicans, while B. garinii and B. bavariensis were associated with neuroborreliosis. The samples in our study belonged to 251 different STs, of which 94 are newly described, adding to the overall picture of the genetic diversity of Borrelia genospecies. The fraction of STs that were isolated from human samples was significantly higher for the genospecies that are known to be maintained in enzootic cycles by mammals (B. afzelii, B. bavariensis, and Borrelia spielmanii) than for genospecies that are maintained by birds (B. garinii and B. valaisiana) or lizards (B. lusitaniae). We found six multilocus sequence types that were significantly associated to clinical manifestations in humans and five IGS haplotypes that were associated with the human LB cases. While IGS could perform just as well as the housekeeping genes in the MLST scheme for predicting the infectivity of B. burgdorferi s.l., the advantage of MLST is that it can also capture the differential invasiveness of the various STs.
authors.affiliation: Laboratory for Zoonoses and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands. Electronic address: claudia.coipan@rivm.nl.
authors.forename: E Claudia
authors.initials: EC
authors.lastname: Coipan
authors.affiliation: Laboratory for Zoonoses and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Setareh
authors.initials: S
authors.lastname: Jahfari
authors.affiliation: Laboratory for Zoonoses and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Manoj
authors.initials: M
authors.lastname: Fonville
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: G Anneke
authors.initials: GA
authors.lastname: Oei
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Lodewijk
authors.initials: L
authors.lastname: Spanjaard
authors.affiliation: Laboratory for Zoonoses and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Takumi
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joppe W R
authors.initials: JW
authors.lastname: Hovius
authors.affiliation: Laboratory for Zoonoses and Environmental Microbiology, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Hein
authors.initials: H
authors.lastname: Sprong
mesh_terms: D000818:Animals; D001096:Arachnid Vectors / Q000382:microbiology*; D025065:Borrelia burgdorferi / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D021901:DNA, Intergenic / Q000235:genetics*; D005838:Genotype; D006801:Humans; D018884:Ixodes / Q000382:microbiology*; D008193:Lyme Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000382:microbiology; D008297:Male; D058885:Multilocus Sequence Typing; D009426:Netherlands / Q000453:epidemiology; D010802:Phylogeny; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012341:RNA, Ribosomal, 5S / Q000235:genetics
chemical_list: D021901:DNA, Intergenic; D012338:RNA, Ribosomal, 23S; D012341:RNA, Ribosomal, 5S
keywords: 5S-23S rDNA intergenic spacer; Acrodermatitis chronica atrophicans; Borrelia burgdorferi s.l.; Erythema migrans; Multilocus sequence typing; Neuroborreliosis