An ospA frame shift, identified from DNA in Lyme arthritis synovial fluid, results in an outer surface protein A that does not bind protective antibodies.
Passive immunization with murine or human Abs to outer surface protein A (OspA) can protect mice against Borrelia burgdorferi, but OspA Abs elicited during natural infection in mice or humans are unable to clear the spirochete from the infected host. To examine Ab binding by OspA during the course of human infection, we amplified the operon encoding full-length ospA and ospB from synovial fluids of a patient with chronic Lyme arthritis, the first such recoveries from human material, at four separate time points over 4.5 mo, and expressed OspA in Escherichia coli. OspA mAbs that passively protected mice from infection did not bind one of the expressed OspAs, because of a deletion in ospA that resulted in a frame shift and premature stop codon near the carboxyl terminus. However, expressed OspA from a later synovial fluid sample did not contain this deletion. Thus, although altered forms of OspA, which potentially can influence host immune effectiveness, do occur in the human host, they cannot be the only factors responsible for microbial persistence.
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis* / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology; D001170:Arthritis, Infectious / Q000276:immunology / Q000382:microbiology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000276:immunology; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000235:genetics* / Q000472:pathogenicity; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D013582:Synovial Fluid / Q000382:microbiology*
D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; C072045:OspA protein