Universidad Peruana Cayetano Heredia

Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL of Treponema pallidum

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dc.contributor.author Haynes, Austin M.
dc.contributor.author Fernandez, Mark
dc.contributor.author Romeis, Emily
dc.contributor.author Mitjà, Oriol
dc.contributor.author Konda, Kelika A.
dc.contributor.author Vargas Rivera, Silver Keith
dc.contributor.author Eguiluz, Maria
dc.contributor.author Caceres Palacios, Carlos Fernando
dc.contributor.author Klausner, Jeffrey D.
dc.contributor.author Giacani, Lorenzo
dc.date.accessioned 2021-04-13T20:50:59Z
dc.date.available 2021-04-13T20:50:59Z
dc.date.issued 2021
dc.identifier.uri https://hdl.handle.net/20.500.12866/9131
dc.description.abstract BACKGROUND: An effective syphilis vaccine should elicit antibodies to Treponema pallidum subsp. pallidum (T. p. pallidum) surface antigens to induce pathogen clearance through opsonophagocytosis. Although the combination of bioinformatics, structural, and functional analyses of T. p. pallidum genes to identify putative outer membrane proteins (OMPs) resulted in a list of potential vaccine candidates, still very little is known about whether and how transcription of these genes is regulated during infection. This knowledge gap is a limitation to vaccine design, as immunity generated to an antigen that can be down-regulated or even silenced at the transcriptional level without affecting virulence would not induce clearance of the pathogen, hence allowing disease progression. PRINCIPAL FINDINGS: We report here that tp1031, the T. p. pallidum gene encoding the putative OMP and vaccine candidate TprL is differentially expressed in several T. p. pallidum strains, suggesting transcriptional regulation. Experimental identification of the tprL transcriptional start site revealed that a homopolymeric G sequence of varying length resides within the tprL promoter and that its length affects promoter activity compatible with phase variation. Conversely, in the closely related pathogen T. p. subsp. pertenue, the agent of yaws, where a naturally-occurring deletion has eliminated the tprL promoter region, elements necessary for protein synthesis, and part of the gene ORF, tprL transcription level are negligible compared to T. p. pallidum strains. Accordingly, the humoral response to TprL is absent in yaws-infected laboratory animals and patients compared to syphilis-infected subjects. CONCLUSION: The ability of T. p. pallidum to stochastically vary tprL expression should be considered in any vaccine development effort that includes this antigen. The role of phase variation in contributing to T. p. pallidum antigenic diversity should be further studied. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartofseries PLoS Neglected Tropical Diseases
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Article en_US
dc.subject controlled study en_US
dc.subject human en_US
dc.subject male en_US
dc.subject nonhuman en_US
dc.subject animal experiment en_US
dc.subject mass spectrometry en_US
dc.subject enzyme linked immunosorbent assay en_US
dc.subject infectious agent en_US
dc.subject genome-wide association study en_US
dc.subject gene expression en_US
dc.subject protein expression en_US
dc.subject affinity chromatography en_US
dc.subject agar gel electrophoresis en_US
dc.subject alkaline phosphatase en_US
dc.subject ampicillin en_US
dc.subject antigen en_US
dc.subject antigenic variation en_US
dc.subject bacterial gene en_US
dc.subject cellular immunity en_US
dc.subject complementary DNA en_US
dc.subject computer model en_US
dc.subject epitope en_US
dc.subject gene cluster en_US
dc.subject gene deletion en_US
dc.subject goat en_US
dc.subject green fluorescent protein en_US
dc.subject guanosine en_US
dc.subject humoral immunity en_US
dc.subject immunology en_US
dc.subject molecular cloning en_US
dc.subject nucleotide sequence en_US
dc.subject open reading frame en_US
dc.subject outer membrane protein en_US
dc.subject Pasteurella multocida en_US
dc.subject phase variation en_US
dc.subject promoter region en_US
dc.subject protein purification en_US
dc.subject protein synthesis en_US
dc.subject rabbit model en_US
dc.subject reverse transcription polymerase chain reaction en_US
dc.subject RNA extraction en_US
dc.subject skin defect en_US
dc.subject spirochete en_US
dc.subject stochastic model en_US
dc.subject syphilis en_US
dc.subject transcription initiation site en_US
dc.subject Treponema pallidum en_US
dc.subject vaccine en_US
dc.subject yaws en_US
dc.title Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL of Treponema pallidum en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.pntd.0008812
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.06
dc.relation.issn 1935-2735


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