title: The failure of immune response evasion by linear plasmid 28-1-deficient Borrelia burgdorferi is attributable to persistent expression of an outer surface protein.
abstract: Infectivity and persistence by Borrelia burgdorferi, the etiologic agent of Lyme disease, rely stringently on regulatory events. Among these is the downregulation of lipoprotein antigen expression, exemplified by outer surface protein C (OspC), at the advent of specific immunity in the mammalian host. B. burgdorferi spirochetes that lack the linear plasmid 28-1 (lp28-1) succumb to the host's immune response. We thus explored the notion that these two phenomena were related--that lp28-1(-) organisms fail to downregulate ospC and thus are cleared following the appearance of anti-OspC antibody in the murine host. The lp-28-1(-) isolate and a wild-type (wt) isolate bearing the complete set of plasmids were grown in dialysis membrane chambers that were implanted into rat peritoneal cavities. Analysis of mRNA and protein from these cultures showed that OspC expression levels by lp28-1(-) organisms are abnormally high in vivo. A time course analysis of ospC expression in tissues following infection indicates also that temporal diminution of the dominant antigen OspC is impaired in lp28-1(-) spirochetes. Finally, passive transfer of monoclonal OspC-specific antibody into SCID mice 8 days postinfection cleared lp28-1(-) spirochetes, yet the wt organisms persisted in a majority of animals. These findings indicate that incomplete repression of OspC by lp28-1(-) organisms renders them susceptible to immune-mediated clearance. The lp28-1 plasmid must harbor one or more genes involved in OspC downregulation.
authors.affiliation: Divisions of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana 70433, USA.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Embers
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.forename: Tara
authors.initials: T
authors.lastname: Ooms
authors.forename: Mario T
authors.initials: MT
authors.lastname: Philipp
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000096:biosynthesis*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis*; D025065:Borrelia burgdorferi / Q000276:immunology* / Q000472:pathogenicity*; D015536:Down-Regulation; D015964:Gene Expression Regulation, Bacterial; D008074:Lipoproteins / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D010957:Plasmids
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D008074:Lipoproteins; C079616:OspC protein