Transcriptional regulation of the Borrelia burgdorferi antigenically variable VlsE surface protein.
The Lyme disease agent Borrelia burgdorferi can persistently infect humans and other animals despite host active immune responses. This is facilitated, in part, by the vls locus, a complex system consisting of the vlsE expression site and an adjacent set of 11 to 15 silent vls cassettes. Segments of nonexpressed cassettes recombine with the vlsE region during infection of mammalian hosts, resulting in combinatorial antigenic variation of the VlsE outer surface protein. We now demonstrate that synthesis of VlsE is regulated during the natural mammal-tick infectious cycle, being activated in mammals but repressed during tick colonization. Examination of cultured B. burgdorferi cells indicated that the spirochete controls vlsE transcription levels in response to environmental cues. Analysis of PvlsE::gfp fusions in B. burgdorferi indicated that VlsE production is controlled at the level of transcriptional initiation, and regions of 5' DNA involved in the regulation were identified. Electrophoretic mobility shift assays detected qualitative and quantitative changes in patterns of protein-DNA complexes formed between the vlsE promoter and cytoplasmic proteins, suggesting the involvement of DNA-binding proteins in the regulation of vlsE, with at least one protein acting as a transcriptional activator.
Bykowski
Tomasz
T
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, MS 415, Chandler Medical Center, Lexington, KY 40536-0298, USA.
Babb
Kelly
K
von Lackum
Kate
K
Riley
Sean P
SP
Norris
Steven J
SJ
Stevenson
Brian
B
D020121:5' Untranslated Regions; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D001096:Arachnid Vectors / Q000378:metabolism* / Q000382:microbiology; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006863:Hydrogen-Ion Concentration; D018884:Ixodes / Q000378:metabolism* / Q000382:microbiology; D007814:Larva / Q000378:metabolism / Q000382:microbiology; D008018:Life Cycle Stages; D008074:Lipoproteins / Q000096:biosynthesis* / Q000235:genetics; D008193:Lyme Disease / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009758:Nymph / Q000378:metabolism / Q000382:microbiology; D013696:Temperature; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D014774:Virulence
D020121:5' Untranslated Regions; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008074:Lipoproteins; C105546:VlsE protein, Borrelia burgdorferi