Variable VlsE Is Critical for Host Reinfection by the Lyme Disease Spirochete

Abstract

Many pathogens make use of antigenic variation as a way to evade the host immune response. A key mechanism for immune evasion and persistent infection by the Lyme disease spirochete, Borrelia burgdorferi, is antigenic variation of the VlsE surface protein. Recombination results in changes in the VlsE surface protein that prevent recognition by VlsE-specific antibodies in the infected host. Despite the presence of a substantial number of additional proteins residing on the bacterial surface, VlsE is the only known antigen that exhibits ongoing variation of its surface epitopes. This suggests that B. burgdorferi may utilize a VlsE-mediated system for immune avoidance of its surface antigens. To address this, the requirement of VlsE for host reinfection by the Lyme disease pathogen was investigated. Host-adapted wild type and VlsE mutant spirochetes were used to reinfect immunocompetent mice that had naturally cleared an infection with a VlsE-deficient clone. Our results demonstrate that variable VlsE is necessary for reinfection by B. burgdorferi, and this ability is directly related to evasion of the host antibody response. Moreover, the data presented here raise the possibility that VlsE prevents recognition of B. burgdorferi surface antigens from host antibodies. Overall, our findings represent a significant advance in our knowledge of immune evasion by B. burgdorferi, and provide insight to the possible mechanisms involved in VlsE-mediated immune avoidance.

Bacterial Heterogeneity Is a Requirement for Host Superinfection by the Lyme Disease Spirochete

“…Previous data have shown that wild-type B. burgdorferi can reinfect mice only when it has been host adapted or tick derived (22,29). For this reason, superinfection was performed using hostadapted B. burgdorferi (Fig.…”

“…B. burgdorferi clones from frozen glycerol stock were passaged no more than two times in vitro prior to use in mouse infection assays. Ear tissues were derived from infected SCID mice at day 28 postinfection as previously described (22,25) and stored at Ϫ80°C until use. Immunodeficient SCID mice were used to generate host-adapted B. burgdorferi due to the lack of their ability to clear infection by the vls mutant clones (21,22).…”

“…Ear tissues were derived from infected SCID mice at day 28 postinfection as previously described (22,25) and stored at Ϫ80°C until use. Immunodeficient SCID mice were used to generate host-adapted B. burgdorferi due to the lack of their ability to clear infection by the vls mutant clones (21,22). For tissue transplantation, ear pinnae were excised into small, circular pieces (3 mm in diameter) by a sterile ear punch and subcutaneously inserted through a skin incision in the lumbar region (two pieces per mouse).…”

ROLE OF VlsE/C6 ANTIGEN AS A MARKER FOR EARLY LYME BORRELIOSIS DIAGNOSIS AND MONITORING THE EFFECTIVENESS OF ITS TREATMENT

“…It seems that the key role in spirochete survival in the host, which was also shown in mouse models, is the loss of plasmid lp28-1 encoding the sequence of the expressed VlsE protein, which results in a significant decrease in infectivity [8,9]. As Rogovskyy et al indicate, the variability of VlsE protein is an essential factor for Borrelia burgdorferi reinfection [10]. The results obtained by the researchers confirm the key role of VlsE in avoiding the host's immune response.…”

Presence of Arp Specifically Contributes to Joint Tissue Edema Associated with Early-Onset Lyme Arthritis

“…The strategy for this involved reconstituting the arp gene back onto the lp28-1 plasmid harboring the arp deletion (Fig. 1C) (38). Previous studies have shown that transcriptional regulation of some B. burgdorferi genes is dependent on the topology (i.e., linear or circular) of the encoding genetic element (39).…”