Essential protective role attributed to the surface lipoproteins of Borrelia burgdorferi against innate defences

Abstract

SummaryTo initiate infection, a microbial pathogen must be able to evade innate immunity. Here we show that the Lyme disease spirochete Borrelia burgdorferi depends on its surface lipoproteins for protection against innate defences. The deficiency for OspC, an abundantly expressed surface lipoprotein during early infection, led to quick clearance of B. burgdorferi after inoculation into the skin of SCID mice. Increasing expression of any of the four randomly chosen surface lipoproteins, OspA, OspE, VlsE or DbpA, fully protected the ospC mutant from elimination from the skin tissue of SCID mice; moreover, increased OspA, OspE or VlsE expression allowed the mutant to cause disseminated infection and restored the ability to effectively colonize both joint and skin tissues, albeit the dissemination process was much slower than that of the mutant restored with OspC expression. When the ospC mutant was modified to express OspA under control of the ospC regulatory elements, it registered only a slight increase in the 50% infectious dose than the control in SCID mice but a dramatic increase in immunocompetent mice. Taken together, the study demonstrated that the surface lipoproteins provide B. burgdorferi with an essential protective function against host innate elimination.

BB0250 of Borrelia burgdorferi Is a Conserved and Essential Inner Membrane Protein Required for Cell Division

“…We repeatedly attempted to replace the bb0250 locus in B. burgdorferi B31 with a gentamicin resistance cassette using established methods (37,38). Unfortunately, no gentamicin-resistant clones were isolated that did not harbor an amplifiable copy of bb0250 (data not shown).…”

Overexpression of CsrA (BB0184) Alters the Morphology and Antigen Profiles ofBorrelia burgdorferi

“…Previous studies have shown the advantages of overexpression of select genes coding for lipoproteins in B. burgdorferi, facilitating evaluation of their contributions in terms of adherence and infectivity (81,83). The methodology was to replace the native promoters of these genes with constitutive borrelial promoters to relieve the need for appropriate signals critical for their continued expression (82).…”

Functional Equivalence of OspA and OspB, but Not OspC, in Tick Colonization by Borrelia burgdorferi

“…Over the past several years, a body of data has accumulated that indicates that the major outer surface proteins of B. burgdorferi perform functionally overlapping roles at different points in the mouse-tick infectious cycle (27,29). The ability of OspC to substitute for VlsE, albeit imperfectly, demonstrates that the role within mammals is not dependent on protein sequence specificity.…”

“…To do so, we demonstrated that OspC can take the place of VlsE during the infection of an immunodeficient animal, which will not make antibodies that would lead to the clearance of OspC-producing spirochetes (29). In contrast, VlsE and OspA could not replace OspC during early mammalian infection, although others have found conditions in which they partially substituted for OspC (27). Our conclusion was that OspC and VlsE carry out similar basic functions but are specialized to the time and context in which they are normally produced.…”

“…VlsE is required for persistent infection, except in immunocompromised mice (16,17). We and others (27)(28)(29) have begun to address the possibility that the three major lipoproteins perform overlapping functions at the different stages of the infectious cycle. To do so, we demonstrated that OspC can take the place of VlsE during the infection of an immunodeficient animal, which will not make antibodies that would lead to the clearance of OspC-producing spirochetes (29).…”