The Coxiella burnetii T4SS Effector AnkF Is Important for Intracellular Replication
Coxiella burnetii is an obligate intracellular pathogen and the causative agent of the zoonotic disease Q fever. Following uptake by alveolar macrophages, the pathogen replicates in an acidic phagolysosomal vacuole, the C. burnetii-containing vacuole (CCV). Effector proteins translocated into the ho...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2020.559915/full |
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| author | Julian Pechstein Jan Schulze-Luehrmann Stephanie Bisle Franck Cantet Paul A. Beare Martha Ölke Matteo Bonazzi Christian Berens Anja Lührmann |
| author_facet | Julian Pechstein Jan Schulze-Luehrmann Stephanie Bisle Franck Cantet Paul A. Beare Martha Ölke Matteo Bonazzi Christian Berens Anja Lührmann |
| author_sort | Julian Pechstein |
| collection | DOAJ |
| description | Coxiella burnetii is an obligate intracellular pathogen and the causative agent of the zoonotic disease Q fever. Following uptake by alveolar macrophages, the pathogen replicates in an acidic phagolysosomal vacuole, the C. burnetii-containing vacuole (CCV). Effector proteins translocated into the host cell by the type IV secretion system (T4SS) are important for the establishment of the CCV. Here we focus on the effector protein AnkF and its role in establishing the CCV. The C. burnetii AnkF knock out mutant invades host cells as efficiently as wild-type C. burnetii, but this mutant is hampered in its ability to replicate intracellularly, indicating that AnkF might be involved in the development of a replicative CCV. To unravel the underlying reason(s), we searched for AnkF interactors in host cells and identified vimentin through a yeast two-hybrid approach. While AnkF does not alter vimentin expression at the mRNA or protein levels, the presence of AnkF results in structural reorganization and vesicular co-localization with recombinant vimentin. Ectopically expressed AnkF partially accumulates around the established CCV and endogenous vimentin is recruited to the CCV in a time-dependent manner, suggesting that AnkF might attract vimentin to the CCV. However, knocking-down endogenous vimentin does not affect intracellular replication of C. burnetii. Other cytoskeletal components are recruited to the CCV and might compensate for the lack of vimentin. Taken together, AnkF is essential for the establishment of the replicative CCV, however, its mode of action is still elusive. |
| first_indexed | 2024-12-17T13:32:43Z |
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| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-17T13:32:43Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-4abaf91bfbe14e8f9d5564f29a367a122022-12-21T21:46:32ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-11-011010.3389/fcimb.2020.559915559915The Coxiella burnetii T4SS Effector AnkF Is Important for Intracellular ReplicationJulian Pechstein0Jan Schulze-Luehrmann1Stephanie Bisle2Franck Cantet3Paul A. Beare4Martha Ölke5Matteo Bonazzi6Christian Berens7Anja Lührmann8Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyInstitut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier, Montpellier, FranceCoxiella Pathogenesis Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United StatesMikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyInstitut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier, Montpellier, FranceFriedrich-Loeffler-Institut, Institut für Molekulare Pathogenese, Jena, GermanyMikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyCoxiella burnetii is an obligate intracellular pathogen and the causative agent of the zoonotic disease Q fever. Following uptake by alveolar macrophages, the pathogen replicates in an acidic phagolysosomal vacuole, the C. burnetii-containing vacuole (CCV). Effector proteins translocated into the host cell by the type IV secretion system (T4SS) are important for the establishment of the CCV. Here we focus on the effector protein AnkF and its role in establishing the CCV. The C. burnetii AnkF knock out mutant invades host cells as efficiently as wild-type C. burnetii, but this mutant is hampered in its ability to replicate intracellularly, indicating that AnkF might be involved in the development of a replicative CCV. To unravel the underlying reason(s), we searched for AnkF interactors in host cells and identified vimentin through a yeast two-hybrid approach. While AnkF does not alter vimentin expression at the mRNA or protein levels, the presence of AnkF results in structural reorganization and vesicular co-localization with recombinant vimentin. Ectopically expressed AnkF partially accumulates around the established CCV and endogenous vimentin is recruited to the CCV in a time-dependent manner, suggesting that AnkF might attract vimentin to the CCV. However, knocking-down endogenous vimentin does not affect intracellular replication of C. burnetii. Other cytoskeletal components are recruited to the CCV and might compensate for the lack of vimentin. Taken together, AnkF is essential for the establishment of the replicative CCV, however, its mode of action is still elusive.https://www.frontiersin.org/articles/10.3389/fcimb.2020.559915/fullQ fevertype IV secretion systemeffector proteinvimentinphagosomeCoxiella burnetii |
| spellingShingle | Julian Pechstein Jan Schulze-Luehrmann Stephanie Bisle Franck Cantet Paul A. Beare Martha Ölke Matteo Bonazzi Christian Berens Anja Lührmann The Coxiella burnetii T4SS Effector AnkF Is Important for Intracellular Replication Frontiers in Cellular and Infection Microbiology Q fever type IV secretion system effector protein vimentin phagosome Coxiella burnetii |
| title | The Coxiella burnetii T4SS Effector AnkF Is Important for Intracellular Replication |
| title_full | The Coxiella burnetii T4SS Effector AnkF Is Important for Intracellular Replication |
| title_fullStr | The Coxiella burnetii T4SS Effector AnkF Is Important for Intracellular Replication |
| title_full_unstemmed | The Coxiella burnetii T4SS Effector AnkF Is Important for Intracellular Replication |
| title_short | The Coxiella burnetii T4SS Effector AnkF Is Important for Intracellular Replication |
| title_sort | coxiella burnetii t4ss effector ankf is important for intracellular replication |
| topic | Q fever type IV secretion system effector protein vimentin phagosome Coxiella burnetii |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2020.559915/full |
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