WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation
Invading pathogens provoke the autophagic machinery and, in a process termed xenophagy, the host cell survives because autophagy is employed as a safeguard for pathogens that escaped phagosomes. However, some pathogens can manipulate the autophagic pathway and replicate within the niche of generated...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2012/179207 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832559865833193472 |
|---|---|
| author | Mario Mauthe Wenqi Yu Oleg Krut Martin Krönke Friedrich Götz Horst Robenek Tassula Proikas-Cezanne |
| author_facet | Mario Mauthe Wenqi Yu Oleg Krut Martin Krönke Friedrich Götz Horst Robenek Tassula Proikas-Cezanne |
| author_sort | Mario Mauthe |
| collection | DOAJ |
| description | Invading pathogens provoke the autophagic machinery and, in a process termed xenophagy, the host cell survives because autophagy is employed as a safeguard for pathogens that escaped phagosomes. However, some pathogens can manipulate the autophagic pathway and replicate within the niche of generated autophagosome-like vesicles. By automated fluorescence-based high content analyses, we demonstrate that Staphylococcus aureus strains (USA300, HG001, SA113) stimulate autophagy and become entrapped in intracellular PtdIns(3)P-enriched vesicles that are decorated with human WIPI-1, an essential PtdIns(3)P effector of canonical autophagy and membrane protein of both phagophores and autophagosomes. Further, agr-positive S. aureus (USA300, HG001) strains were more efficiently entrapped in WIPI-1 positive autophagosome-like vesicles when compared to agr-negative cells (SA113). By confocal and electron microscopy we provide evidence that single- and multiple-Staphylococci entrapped undergo cell division. Moreover, the number of WIPI-1 positive autophagosome-like vesicles entrapping Staphylococci significantly increased upon (i) lysosomal inhibition by bafilomycin A1 and (ii) blocking PIKfyve-mediated PtdIns(3,5)P2 generation by YM201636. In summary, our results provide evidence that the PtdIns(3)P effector function of WIPI-1 is utilized during xenophagy of Staphylococcus aureus. We suggest that invading S. aureus cells become entrapped in autophagosome-like WIPI-1 positive vesicles targeted for lysosomal degradation in nonprofessional host cells. |
| format | Article |
| id | doaj-art-dc24fe4a08464b80a1b13a06960cec14 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-dc24fe4a08464b80a1b13a06960cec142025-02-03T01:29:10ZengWileyInternational Journal of Cell Biology1687-88761687-88842012-01-01201210.1155/2012/179207179207WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal DegradationMario Mauthe0Wenqi Yu1Oleg Krut2Martin Krönke3Friedrich Götz4Horst Robenek5Tassula Proikas-Cezanne6Autophagy Laboratory, Interfaculty Institute for Cell Biology, Eberhard Karls University Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, GermanyMicrobial Genetics, Interfaculty Institute for Microbiology and Infectious Medicine, University of Tübingen, 72076 Tübingen, GermanyInstitute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, GermanyInstitute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, GermanyMicrobial Genetics, Interfaculty Institute for Microbiology and Infectious Medicine, University of Tübingen, 72076 Tübingen, GermanyLeibniz Institute for Arteriosclerosis Research, University of Münster, 48149 Münster, GermanyAutophagy Laboratory, Interfaculty Institute for Cell Biology, Eberhard Karls University Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, GermanyInvading pathogens provoke the autophagic machinery and, in a process termed xenophagy, the host cell survives because autophagy is employed as a safeguard for pathogens that escaped phagosomes. However, some pathogens can manipulate the autophagic pathway and replicate within the niche of generated autophagosome-like vesicles. By automated fluorescence-based high content analyses, we demonstrate that Staphylococcus aureus strains (USA300, HG001, SA113) stimulate autophagy and become entrapped in intracellular PtdIns(3)P-enriched vesicles that are decorated with human WIPI-1, an essential PtdIns(3)P effector of canonical autophagy and membrane protein of both phagophores and autophagosomes. Further, agr-positive S. aureus (USA300, HG001) strains were more efficiently entrapped in WIPI-1 positive autophagosome-like vesicles when compared to agr-negative cells (SA113). By confocal and electron microscopy we provide evidence that single- and multiple-Staphylococci entrapped undergo cell division. Moreover, the number of WIPI-1 positive autophagosome-like vesicles entrapping Staphylococci significantly increased upon (i) lysosomal inhibition by bafilomycin A1 and (ii) blocking PIKfyve-mediated PtdIns(3,5)P2 generation by YM201636. In summary, our results provide evidence that the PtdIns(3)P effector function of WIPI-1 is utilized during xenophagy of Staphylococcus aureus. We suggest that invading S. aureus cells become entrapped in autophagosome-like WIPI-1 positive vesicles targeted for lysosomal degradation in nonprofessional host cells.http://dx.doi.org/10.1155/2012/179207 |
| spellingShingle | Mario Mauthe Wenqi Yu Oleg Krut Martin Krönke Friedrich Götz Horst Robenek Tassula Proikas-Cezanne WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation International Journal of Cell Biology |
| title | WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation |
| title_full | WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation |
| title_fullStr | WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation |
| title_full_unstemmed | WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation |
| title_short | WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation |
| title_sort | wipi 1 positive autophagosome like vesicles entrap pathogenic staphylococcus aureus for lysosomal degradation |
| url | http://dx.doi.org/10.1155/2012/179207 |
| work_keys_str_mv | AT mariomauthe wipi1positiveautophagosomelikevesiclesentrappathogenicstaphylococcusaureusforlysosomaldegradation AT wenqiyu wipi1positiveautophagosomelikevesiclesentrappathogenicstaphylococcusaureusforlysosomaldegradation AT olegkrut wipi1positiveautophagosomelikevesiclesentrappathogenicstaphylococcusaureusforlysosomaldegradation AT martinkronke wipi1positiveautophagosomelikevesiclesentrappathogenicstaphylococcusaureusforlysosomaldegradation AT friedrichgotz wipi1positiveautophagosomelikevesiclesentrappathogenicstaphylococcusaureusforlysosomaldegradation AT horstrobenek wipi1positiveautophagosomelikevesiclesentrappathogenicstaphylococcusaureusforlysosomaldegradation AT tassulaproikascezanne wipi1positiveautophagosomelikevesiclesentrappathogenicstaphylococcusaureusforlysosomaldegradation |