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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...

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Autores principales: Kim, Hwan Keun, Premaratna, Ranjan, Missiakas, Dominique M., Schneewind, Olaf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
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.
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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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