Borrelia burgdorferielongation factor EF-Tu is an immunogenic protein during Lyme borreliosis

Abstract

Borrelia burgdorferi, the etiological agent of Lyme disease, does not produce lipopolysaccharide but expresses a large number of lipoproteins on its cell surface. These outer membrane lipoproteins are highly immunogenic and have been used for serodiagnosis of Lyme disease. Recent studies have shown that highly conserved cytosolic proteins such as enolase and elongation factor Tu (EF-Tu) unexpectedly localized on the surface of bacteria including B. burgdorferi, and surface-localized enolase has shown to contribute to the enzootic cycle of B. burgdorferi. In this study, we studied the immunogenicity, surface localization, and function of B. burgdorferi EF-Tu. We found that EF-Tu is highly immunogenic in mice, and EF-Tu antibodies were readily detected in Lyme disease patients. On the other hand, active immunization studies showed that EF-Tu antibodies did not protect mice from infection when challenged with B. burgdorferi via either needle inoculation or tick bites. Borrelial mouse-tick cycle studies showed that EF-Tu antibodies also did not block B. burgdorferi migration and survival in ticks. Consistent with these findings, we found that EF-Tu primarily localizes in the protoplasmic cylinder of spirochetes and is not on the surface of B. burgdorferi. Taken together, our studies suggest that B. burgdorferi EF-Tu is not surfaced exposed, but it is highly immunogenic and is a potential serodiagnostic marker for Lyme borreliosis.

Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model

“…Table 3 ). In support of our findings, EF-Tu has been shown to exhibit many functions associated with pathogenesis and to elicit antibody responses during infection by several bacteria, and by a meningococcal group B OMV vaccine 48 – 51 . The role of PotF3 in gonococcal pathogenesis and immunity is unknown at this point; however, PotF2 appears to function as a polyamine-binding protein, and spermine inhibits gonococcal biofilm formation 52 .…”

Identification of Borrelia protein candidates in mouse skin for potential diagnosis of disseminated Lyme borreliosis

“…For these mice, we got a large panel of Borrelia proteins including flagellin and VlsE, but also L-lactate dehydrogenase, neutrophil activating protein (Nap), enolase, oligopeptide ABC transporter, and Elongation factor Tu. Elongation factor Tu is a highly immunogenic protein which is primarily found in the protoplasmic cylinder of spirochetes and is not on the surface of B. burgdorferi 51 . Nap is one of the main Borrelia proteins involved in the pathogenesis of the early stages of Lyme arthritis.…”

Cross—reactivity of antibodies against microbial proteins to human tissues as basis of Crohn’s disease and other autoimmune diseases

“…tuberculosis and E.coli (43). EF-Tu from B. burgdorferi was found to be immunogenic during Lyme disease (44). It is plausible that the antibodies reacting to the extracts of B.…”