Identification of an ospC operator critical for immune evasion of Borrelia burgdorferi.
Timely expression of the outer surface protein C (OspC) is crucial for the pathogenic strategy of the Lyme disease spirochete Borrelia burgdorferi. The pathogen abundantly expresses OspC during initial infection when the antigen is required, but downregulates when its presence poses a threat to the spirochetes once the anti-OspC humoral response has developed. Here, we show that a large palindromic sequence immediately upstream of the ospC promoter is essential for the repression of ospC expression during murine infection and for the ability of B. burgdorferi to evade specific OspC humoral immunity. Deletion of the sequence completely diminished the ability of B. burgdorferi to avoid clearance by transferred OspC antibody in SCID mice. B. burgdorferi lacking the regulatory element was able to initiate infection but unable to persist in immunocompetent mice. Taken together, the regulatory element immediately upstream of the ospC promoter serves as an operator that may interact with an unidentified repressor(s) to negatively regulate ospC expression and is essential for the immune evasion of B. burgdorferi.
Xu
Qilong
Q
Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
McShan
Kristy
K
Liang
Fang Ting
FT
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000235:genetics / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009154:Mutation; D009875:Operator Regions, Genetic; D017384:Sequence Deletion
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C079616:OspC protein