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The anti-apoptotic Coxiella burnetii effector protein AnkG is a strain specific virulence factor

The ability to inhibit host cell apoptosis is important for the intracellular replication of the obligate intracellular pathogen Coxiella burnetii, as it allows the completion of the lengthy bacterial replication cycle. Effector proteins injected into the host cell by the C. burnetii type IVB secret...

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Autores principales: Schäfer, Walter, Schmidt, Teresa, Cordsmeier, Arne, Borges, Vítor, Beare, Paul A., Pechstein, Julian, Schulze-Luehrmann, Jan, Holzinger, Jonas, Wagner, Nicole, Berens, Christian, Heydel, Carsten, Gomes, João Paulo, Lührmann, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506536/
https://www.ncbi.nlm.nih.gov/pubmed/32958854
http://dx.doi.org/10.1038/s41598-020-72340-9
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author Schäfer, Walter
Schmidt, Teresa
Cordsmeier, Arne
Borges, Vítor
Beare, Paul A.
Pechstein, Julian
Schulze-Luehrmann, Jan
Holzinger, Jonas
Wagner, Nicole
Berens, Christian
Heydel, Carsten
Gomes, João Paulo
Lührmann, Anja
author_facet Schäfer, Walter
Schmidt, Teresa
Cordsmeier, Arne
Borges, Vítor
Beare, Paul A.
Pechstein, Julian
Schulze-Luehrmann, Jan
Holzinger, Jonas
Wagner, Nicole
Berens, Christian
Heydel, Carsten
Gomes, João Paulo
Lührmann, Anja
author_sort Schäfer, Walter
collection PubMed
description The ability to inhibit host cell apoptosis is important for the intracellular replication of the obligate intracellular pathogen Coxiella burnetii, as it allows the completion of the lengthy bacterial replication cycle. Effector proteins injected into the host cell by the C. burnetii type IVB secretion system (T4BSS) are required for the inhibition of host cell apoptosis. AnkG is one of these anti-apoptotic effector proteins. The inhibitory effect of AnkG requires its nuclear localization, which depends on p32-dependent intracellular trafficking and importin-α1-mediated nuclear entry of AnkG. Here, we compared the sequences of ankG from 37 C. burnetii isolates and classified them in three groups based on the predicted protein size. The comparison of the three different groups allowed us to identify the first 28 amino acids as essential and sufficient for the anti-apoptotic activity of AnkG. Importantly, only the full-length protein from the first group is a bona fide effector protein injected into host cells during infection and has anti-apoptotic activity. Finally, using the Galleria mellonella infection model, we observed that AnkG from the first group has the ability to attenuate pathology during in vivo infection, as it allows survival of the larvae despite bacterial replication.
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spelling pubmed-75065362020-09-24 The anti-apoptotic Coxiella burnetii effector protein AnkG is a strain specific virulence factor Schäfer, Walter Schmidt, Teresa Cordsmeier, Arne Borges, Vítor Beare, Paul A. Pechstein, Julian Schulze-Luehrmann, Jan Holzinger, Jonas Wagner, Nicole Berens, Christian Heydel, Carsten Gomes, João Paulo Lührmann, Anja Sci Rep Article The ability to inhibit host cell apoptosis is important for the intracellular replication of the obligate intracellular pathogen Coxiella burnetii, as it allows the completion of the lengthy bacterial replication cycle. Effector proteins injected into the host cell by the C. burnetii type IVB secretion system (T4BSS) are required for the inhibition of host cell apoptosis. AnkG is one of these anti-apoptotic effector proteins. The inhibitory effect of AnkG requires its nuclear localization, which depends on p32-dependent intracellular trafficking and importin-α1-mediated nuclear entry of AnkG. Here, we compared the sequences of ankG from 37 C. burnetii isolates and classified them in three groups based on the predicted protein size. The comparison of the three different groups allowed us to identify the first 28 amino acids as essential and sufficient for the anti-apoptotic activity of AnkG. Importantly, only the full-length protein from the first group is a bona fide effector protein injected into host cells during infection and has anti-apoptotic activity. Finally, using the Galleria mellonella infection model, we observed that AnkG from the first group has the ability to attenuate pathology during in vivo infection, as it allows survival of the larvae despite bacterial replication. Nature Publishing Group UK 2020-09-21 /pmc/articles/PMC7506536/ /pubmed/32958854 http://dx.doi.org/10.1038/s41598-020-72340-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Schäfer, Walter
Schmidt, Teresa
Cordsmeier, Arne
Borges, Vítor
Beare, Paul A.
Pechstein, Julian
Schulze-Luehrmann, Jan
Holzinger, Jonas
Wagner, Nicole
Berens, Christian
Heydel, Carsten
Gomes, João Paulo
Lührmann, Anja
The anti-apoptotic Coxiella burnetii effector protein AnkG is a strain specific virulence factor
title The anti-apoptotic Coxiella burnetii effector protein AnkG is a strain specific virulence factor
title_full The anti-apoptotic Coxiella burnetii effector protein AnkG is a strain specific virulence factor
title_fullStr The anti-apoptotic Coxiella burnetii effector protein AnkG is a strain specific virulence factor
title_full_unstemmed The anti-apoptotic Coxiella burnetii effector protein AnkG is a strain specific virulence factor
title_short The anti-apoptotic Coxiella burnetii effector protein AnkG is a strain specific virulence factor
title_sort anti-apoptotic coxiella burnetii effector protein ankg is a strain specific virulence factor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506536/
https://www.ncbi.nlm.nih.gov/pubmed/32958854
http://dx.doi.org/10.1038/s41598-020-72340-9
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