Blog
About

0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Borrelia burgdorferi VlsE Lipoprotein Prevents Antibody Binding to an Arthritis-Related Surface Antigen

      1 , 1 , 2 , *

      Cell reports

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          SUMMARY

          Arp is an immunogenic protein of the Lyme disease spirochete Borrelia burgdorferi and contributes to joint inflammation during infection. Despite Arp eliciting a strong humoral response, antibodies fail to clear the infection. Given previous evidence of immune avoidance mediated by the antigenically variable lipoprotein of B. burgdorferi, VlsE, we use passive immunization assays to examine whether VlsE protects the pathogen from anti-Arp antibodies. The results show that spirochetes are only able to successfully infect passively immunized mice when VlsE is expressed. Subsequent immunofluorescence assays reveal that VlsE prevents binding of Arp-specific antibodies, thereby providing an explanation for the failure of Arp antisera to clear the infection. The results also show that the shielding effect of VlsE is not universal for all B. burgdorferi cell-surface antigens. The findings reported here represent a direct demonstration of VlsE-mediated protection of a specific B. burgdorferi surface antigen through a possible epitope-shielding mechanism.

          In Brief

          Lone and Bankhead report that the antigenically variable VlsE protein of the Lyme disease agent Borrelia burgdorferi can prevent antibody binding to a surface antigen of the pathogen. They show that protection is likely via an epitope-shielding mechanism, thus expanding the current role of VlsE in immune evasion.

          Graphical Abstract

          Related collections

          Most cited references 46

          • Record: found
          • Abstract: found
          • Article: not found

          Lyme borreliosis.

          Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries. Laboratory evidence of infection, mainly serology, is essential for diagnosis, except in the case of typical erythema migrans. Diagnosed cases are usually treated with antibiotics for 2-4 weeks and most patients make an uneventful recovery. No convincing evidence exists to support the use of antibiotics for longer than 4 weeks, or for the persistence of spirochaetes in adequately treated patients. Prevention is mainly accomplished by protecting against tick bites. There is no vaccine available for human beings. Copyright © 2012 Elsevier Ltd. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Lyme disease testing by large commercial laboratories in the United States.

            Laboratory testing is helpful when evaluating patients with suspected Lyme disease (LD). A 2-tiered antibody testing approach is recommended, but single-tier and nonvalidated tests are also used. We conducted a survey of large commercial laboratories in the United States to assess laboratory practices. We used these data to estimate the cost of testing and number of infections among patients from whom specimens were submitted. Large commercial laboratories were asked to report the type and volume of testing conducted nationwide in 2008, as well as the percentage of positive tests for 4 LD-endemic states. The total direct cost of testing was calculated for each test type. These data and test-specific performance parameters available in published literature were used to estimate the number of infections among source patients. Seven participating laboratories performed approximately 3.4 million LD tests on approximately 2.4 million specimens nationwide at an estimated cost of $492 million. Two-tiered testing accounted for at least 62% of assays performed; alternative testing accounted for <3% of assays. The estimated frequency of infection among patients from whom specimens were submitted ranged from 10% to 18.5%. Applied to the total numbers of specimens, this yielded an estimated 240 000 to 444 000 infected source patients in 2008. LD testing is common and costly, with most testing in accordance with diagnostic recommendations. These results highlight the importance of considering clinical and exposure history when interpreting laboratory results for diagnostic and surveillance purposes. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes.

              We have identified and characterized an elaborate genetic system in the Lyme disease spirochete Borrelia burgdorferi that promotes extensive antigenic variation of a surface-exposed lipoprotein, VlsE. A 28 kb linear plasmid of B. burgdorferi B31 (lp28-1) was found to contain a vmp-like sequence (vls) locus that closely resembles the variable major protein (vmp) system for antigenic variation of relapsing fever organisms. Portions of several of the 15 nonexpressed (silent) vls cassette sequences located upstream of vlsE recombined into the central vlsE cassette region during infection of C3H/HeN mice, resulting in antigenic variation of the expressed lipoprotein. This combinatorial variation could potentially produce millions of antigenic variants in the mammalian host.
                Bookmark

                Author and article information

                Journal
                101573691
                39703
                Cell Rep
                Cell Rep
                Cell reports
                2211-1247
                23 March 2020
                17 March 2020
                16 April 2020
                : 30
                : 11
                : 3663-3670.e5
                Affiliations
                [1 ]Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA
                [2 ]Lead Contact
                Author notes

                AUTHOR CONTRIBUTIONS

                Conceptualization, A.G.L. and T.B.; Methodology, A.G.L. and T.B.; Investigation, A.G.L.; Validation, A.G.L.; Formal Analysis, A.G.L. and T.B.; Writing – Original Draft, A.G.L. and T.B.; Writing – Review & Editing, A.G.L. and T.B.; Visualization, A.G.L. and T.B.; Funding Acquisition, T.B.; Resources, T.B.; Supervision, T.B.

                [* ]Correspondence: tbankhead@ 123456wsu.edu
                Article
                NIHMS1578462
                10.1016/j.celrep.2020.02.081
                7162589
                32187539

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                Categories
                Article

                Cell biology

                Comments

                Comment on this article