title: WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation.
abstract: 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 A(1) and (ii) blocking PIKfyve-mediated PtdIns(3,5)P(2) 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.
authors: Autophagy Laboratory, Interfaculty Institute for Cell Biology, Eberhard Karls University Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
authors: Mario
authors: M
authors: Mauthe
authors: Wenqi
authors: W
authors: Yu
authors: Oleg
authors: O
authors: Krut
authors: Martin
authors: M
authors: Krönke
authors: Friedrich
authors: F
authors: Götz
authors: Horst
authors: H
authors: Robenek
authors: Tassula
authors: T
authors: Proikas-Cezanne