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Rickettsia conorii O antigen is the target of bactericidal Weil–Felix antibodies
Rickettsial diseases have long been diagnosed with serum antibodies cross-reactive against Proteus vulgaris (Weil–Felix reaction). Although Weil–Felix antibodies are associated with the development of immunity, their rickettsial target and contribution to disease pathogenesis are not established. He...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765297/ https://www.ncbi.nlm.nih.gov/pubmed/31413191 http://dx.doi.org/10.1073/pnas.1911922116 |
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author | Kim, Hwan Keun Premaratna, Ranjan Missiakas, Dominique M. Schneewind, Olaf |
author_facet | Kim, Hwan Keun Premaratna, Ranjan Missiakas, Dominique M. Schneewind, Olaf |
author_sort | Kim, Hwan Keun |
collection | PubMed |
description | Rickettsial diseases have long been diagnosed with serum antibodies cross-reactive against Proteus vulgaris (Weil–Felix reaction). Although Weil–Felix antibodies are associated with the development of immunity, their rickettsial target and contribution to disease pathogenesis are not established. Here, we developed a transposon for insertional mutagenesis of Rickettsia conorii, isolating variants defective for replication in cultured cells and in spotted fever pathogenesis. Mutations in the polysaccharide synthesis operon (pso) abolish lipopolysaccharide O-antigen synthesis and Weil–Felix serology and alter outer-membrane protein assembly. Unlike wild-type R. conorii, pso mutants cannot elicit bactericidal antibodies that bind O antigen. The pso operon is conserved among rickettsial pathogens, suggesting that bactericidal antibodies targeting O antigen may generate universal immunity that could be exploited to develop vaccines against rickettsial diseases. |
format | Online Article Text |
id | pubmed-6765297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-67652972019-10-02 Rickettsia conorii O antigen is the target of bactericidal Weil–Felix antibodies Kim, Hwan Keun Premaratna, Ranjan Missiakas, Dominique M. Schneewind, Olaf Proc Natl Acad Sci U S A Biological Sciences Rickettsial diseases have long been diagnosed with serum antibodies cross-reactive against Proteus vulgaris (Weil–Felix reaction). Although Weil–Felix antibodies are associated with the development of immunity, their rickettsial target and contribution to disease pathogenesis are not established. Here, we developed a transposon for insertional mutagenesis of Rickettsia conorii, isolating variants defective for replication in cultured cells and in spotted fever pathogenesis. Mutations in the polysaccharide synthesis operon (pso) abolish lipopolysaccharide O-antigen synthesis and Weil–Felix serology and alter outer-membrane protein assembly. Unlike wild-type R. conorii, pso mutants cannot elicit bactericidal antibodies that bind O antigen. The pso operon is conserved among rickettsial pathogens, suggesting that bactericidal antibodies targeting O antigen may generate universal immunity that could be exploited to develop vaccines against rickettsial diseases. National Academy of Sciences 2019-09-24 2019-08-14 /pmc/articles/PMC6765297/ /pubmed/31413191 http://dx.doi.org/10.1073/pnas.1911922116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Kim, Hwan Keun Premaratna, Ranjan Missiakas, Dominique M. Schneewind, Olaf Rickettsia conorii O antigen is the target of bactericidal Weil–Felix antibodies |
title | Rickettsia conorii O antigen is the target of bactericidal Weil–Felix antibodies |
title_full | Rickettsia conorii O antigen is the target of bactericidal Weil–Felix antibodies |
title_fullStr | Rickettsia conorii O antigen is the target of bactericidal Weil–Felix antibodies |
title_full_unstemmed | Rickettsia conorii O antigen is the target of bactericidal Weil–Felix antibodies |
title_short | Rickettsia conorii O antigen is the target of bactericidal Weil–Felix antibodies |
title_sort | rickettsia conorii o antigen is the target of bactericidal weil–felix antibodies |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765297/ https://www.ncbi.nlm.nih.gov/pubmed/31413191 http://dx.doi.org/10.1073/pnas.1911922116 |
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