Development of a sequence-based in silico OspA typing method for Borrelia burgdorferi sensu lato

Lyme disease (LD), caused by spirochete bacteria of the genus , remains the most common vector-borne disease in the northern hemisphere. outer surface protein A (OspA) is an integral surface protein expressed during the tick cycle, and a validated vaccine target. There are at least 20 recognized gen...

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Published inMicrobial genomics Vol. 10; no. 5
Main Authors Lee, Jonathan T, Li, Zhenghui, Nunez, Lorna D, Katzel, Daniel, Perrin, Jr, B Scott, Raghuraman, Varun, Rajyaguru, Urvi, Llamera, Katrina E, Andrew, Lubomira, Anderson, Annaliesa S, Hovius, Joppe W, Liberator, Paul A, Simon, Raphael, Hao, Li
Format Journal Article
LanguageEnglish
Published England Microbiology Society 01.05.2024
Subjects
Antigens, Surface - genetics
Bacterial Outer Membrane Proteins - genetics
Bacterial Vaccines
Borrelia burgdorferi - classification
Borrelia burgdorferi - genetics
Borrelia burgdorferi Group - classification
Borrelia burgdorferi Group - genetics
Computer Simulation
Genome, Bacterial
Genomic Methodologies
High-Throughput Nucleotide Sequencing - methods
Humans
Lipoproteins - genetics
Lyme Disease - microbiology
Phylogeny
Serogroup
Borrelia genospecies
in silico OspA typing
OspA diversity
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Summary:Lyme disease (LD), caused by spirochete bacteria of the genus , remains the most common vector-borne disease in the northern hemisphere. outer surface protein A (OspA) is an integral surface protein expressed during the tick cycle, and a validated vaccine target. There are at least 20 recognized genospecies, that vary in OspA serotype. This study presents a new sequence-based method for OspA typing using next-generation sequence data. Using a compiled database of over 400 genomes encompassing the 4 most common disease-causing genospecies, we characterized OspA diversity in a manner that can accommodate existing and new OspA types and then defined boundaries for classification and assignment of OspA types based on the sequence similarity. To accommodate potential novel OspA types, we have developed a new nomenclature: OspA type (IST). Beyond the ISTs that corresponded to existing OspA serotypes 1-8, we identified nine additional ISTs that cover new OspA variants in (IST9-10), (IST11-12), and other genospecies (IST13-17). The IST typing scheme and associated OspA variants are available as part of the PubMLST spp. database. Compared to traditional OspA serotyping methods, this new computational pipeline provides a more comprehensive and broadly applicable approach for characterization of OspA type and genospecies to support vaccine development.
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Authors (except for J.W.H.) are current or former employees of Pfizer and may, consequently, be shareholders of Pfizer, Inc. Pfizer was involved in the study concept and design, the collection, analysis and interpretation of data, the drafting of the manuscript, and the decision to submit the manuscript for publication. J.W.H. has ongoing research collaborations with Pfizer, Inc., and collaborates, or has collaborated, with Moderna, Antigen Discovery, Inc., Bio-Rad Laboratories, Abbott, and ZEUS Scientific on other projects on Lyme borreliosis. J.W.H. has an application for a provisional patent related to Borrelia antigens pending.
Four supplementary figures and four supplementary tables are available with the online version of this article.
Supplement: All supporting data, code and protocols have been provided within the article or through supplementary data files.
ISSN:2057-5858
2057-5858
DOI:10.1099/mgen.0.001252