The absence of linear plasmid 25 or 28-1 of Borrelia burgdorferi dramatically alters the kinetics of experimental infection via distinct mechanisms.
The 25-kb linear plasmid lp25 and one of the 28-kb linear plasmids (lp28-1) are required for experimental infection in Borrelia burgdorferi, the etiologic agent of Lyme disease. The loss of these plasmids either eliminates infectivity (lp25) or significantly increases the 50% infective dose during a 2-week infection period (lp28-1). This study assessed the kinetics of bacterial dissemination in C3H/HeN mice infected with B. burgdorferi lacking either lp25 or lp28-1, as well as their wild-type parent, and tracked the development of specific borrelial antibodies over a 3-week period. The results indicated that the wild type and the lp28-1(-) strains were able to disseminate throughout the host, whereas the lp25(-) strain was cleared within 48 h of inoculation. While the wild-type B. burgdorferi persisted in tissues for the duration of the study, the lp28-1(-) mutant began clearing at day 8, with no detectable bacteria present by day 18. As expected, the wild-type strain persisted in C3H/HeN mice despite a strong humoral response; however, the lp28-1(-) mutant was cleared coincidently with the development of a modest immunoglobulin M response. The lp28-1(-) mutant was able to disseminate and persist in C3H-scid mice at a level indistinguishable from that of wild-type cells, confirming that acquired immunity was required for clearance in C3H/HeN mice. Thus, within an immunocompetent host, lp28-1-encoded proteins are not required for dissemination but are essential for persistence associated with Lyme borreliosis.
Labandeira-Rey
Maria
M
Department of Medical Microbiology and Immunology, The Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA.
Seshu
J
J
Skare
Jonathan T
JT
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007700:Kinetics; D008193:Lyme Disease / Q000209:etiology* / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009154:Mutation; D010957:Plasmids / Q000235:genetics*; D014774:Virulence / Q000235:genetics
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M