Constitutive expression of outer surface protein C diminishes the ability of Borrelia burgdorferi to evade specific humoral immunity.
The Lyme disease spirochete Borrelia burgdorferi reduces the expression of outer surface protein C (OspC) in response to the development of an anti-OspC humoral response, leading to the hypothesis that the ability to repress OspC expression is critical for the pathogen to proceed to chronic infection. B. burgdorferi was genetically modified to constitutively express OspC by introducing an extra ospC copy fused with the borrelial flagellar gene (flaB) promoter. Such a genetic modification did not reduce infectivity or pathogenicity in severe combined immunodeficiency mice but resulted in clearance of infection by passively transferred OspC antibody. Spirochetes with constitutive ospC expression were unable to establish chronic infections in immunocompetent mice unless they had undergone very destructive mutations in the introduced ospC copy. Two escape mutants were identified; one had all 7 bp deleted between the putative ribosome-binding site and the start codon, ATG, causing a failure in translational initiation, and the other mutant had an insertion of 2 bp between nucleotides 315 and 316, resulting in a nonsense mutation at codon 108. Thus, the ability of B. burgdorferi to repress ospC expression during mammalian infection allows the pathogen to avoid clearance and to preserve the integrity of the important gene for subsequent utilization during its enzootic life cycle.
Xu
Qilong
Q
Department of Pathobiological Sciences, Louisiana State University, Skip Bertman Drive at River Road, Baton Rouge, LA 70803, USA.
Seemanapalli
Sunita V
SV
McShan
Kristy
K
Liang
Fang Ting
FT
D000818:Animals; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000472:pathogenicity*; D018389:Codon, Nonsense; D005408:Flagellin / Q000235:genetics; D018628:Gene Dosage; D015964:Gene Expression Regulation, Bacterial; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D017384:Sequence Deletion; D014169:Transformation, Bacterial
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018389:Codon, Nonsense; C079616:OspC protein; D005408:Flagellin; C416532:flaB flagellin