GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.

Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respective...

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Autores principales: Jessica Rauch, Jessica Barton, Marcel Kwiatkowski, Malte Wunderlich, Pascal Steffen, Kristin Moderzynski, Stefanie Papp, Katharina Höhn, Hella Schwanke, Susanne Witt, Ulricke Richardt, Ute Mehlhoop, Hartmut Schlüter, Verena Pianka, Bernhard Fleischer, Dennis Tappe, Anke Osterloh
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:d807ac1299a043dc8d07555fe1daebc62021-12-02T20:10:47ZGroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.1932-620310.1371/journal.pone.0253084https://doaj.org/article/d807ac1299a043dc8d07555fe1daebc62021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253084https://doaj.org/toc/1932-6203Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.Jessica RauchJessica BartonMarcel KwiatkowskiMalte WunderlichPascal SteffenKristin ModerzynskiStefanie PappKatharina HöhnHella SchwankeSusanne WittUlricke RichardtUte MehlhoopHartmut SchlüterVerena PiankaBernhard FleischerDennis TappeAnke OsterlohPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253084 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jessica Rauch
Jessica Barton
Marcel Kwiatkowski
Malte Wunderlich
Pascal Steffen
Kristin Moderzynski
Stefanie Papp
Katharina Höhn
Hella Schwanke
Susanne Witt
Ulricke Richardt
Ute Mehlhoop
Hartmut Schlüter
Verena Pianka
Bernhard Fleischer
Dennis Tappe
Anke Osterloh
GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.
description Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.
format article
author Jessica Rauch
Jessica Barton
Marcel Kwiatkowski
Malte Wunderlich
Pascal Steffen
Kristin Moderzynski
Stefanie Papp
Katharina Höhn
Hella Schwanke
Susanne Witt
Ulricke Richardt
Ute Mehlhoop
Hartmut Schlüter
Verena Pianka
Bernhard Fleischer
Dennis Tappe
Anke Osterloh
author_facet Jessica Rauch
Jessica Barton
Marcel Kwiatkowski
Malte Wunderlich
Pascal Steffen
Kristin Moderzynski
Stefanie Papp
Katharina Höhn
Hella Schwanke
Susanne Witt
Ulricke Richardt
Ute Mehlhoop
Hartmut Schlüter
Verena Pianka
Bernhard Fleischer
Dennis Tappe
Anke Osterloh
author_sort Jessica Rauch
title GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.
title_short GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.
title_full GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.
title_fullStr GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.
title_full_unstemmed GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi.
title_sort groel is an immunodominant surface-exposed antigen of rickettsia typhi.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/d807ac1299a043dc8d07555fe1daebc6
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