Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells.

Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Uptake by host cells is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can es...

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Autores principales: Kathrin Stelzner, Aziza Boyny, Tobias Hertlein, Aneta Sroka, Adriana Moldovan, Kerstin Paprotka, David Kessie, Helene Mehling, Jan Potempa, Knut Ohlsen, Martin J Fraunholz, Thomas Rudel
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:016ce96c8f4e4388a9897eb4c96ddd962021-12-02T20:00:14ZIntracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells.1553-73661553-737410.1371/journal.ppat.1009874https://doaj.org/article/016ce96c8f4e4388a9897eb4c96ddd962021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009874https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Uptake by host cells is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death after translocation of intracellular S. aureus into the host cell cytoplasm. We demonstrated that loss of staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. In phagocytic cells, where intracellular S. aureus is exclusively localized in the phagosome, staphopain A did not contribute to cytotoxicity. Our study suggests that staphopain A is utilized by S. aureus to exit the epithelial host cell and thus contributes to tissue destruction and dissemination of infection.Kathrin StelznerAziza BoynyTobias HertleinAneta SrokaAdriana MoldovanKerstin PaprotkaDavid KessieHelene MehlingJan PotempaKnut OhlsenMartin J FraunholzThomas RudelPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009874 (2021)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Kathrin Stelzner
Aziza Boyny
Tobias Hertlein
Aneta Sroka
Adriana Moldovan
Kerstin Paprotka
David Kessie
Helene Mehling
Jan Potempa
Knut Ohlsen
Martin J Fraunholz
Thomas Rudel
Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells.
description Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Uptake by host cells is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death after translocation of intracellular S. aureus into the host cell cytoplasm. We demonstrated that loss of staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. In phagocytic cells, where intracellular S. aureus is exclusively localized in the phagosome, staphopain A did not contribute to cytotoxicity. Our study suggests that staphopain A is utilized by S. aureus to exit the epithelial host cell and thus contributes to tissue destruction and dissemination of infection.
format article
author Kathrin Stelzner
Aziza Boyny
Tobias Hertlein
Aneta Sroka
Adriana Moldovan
Kerstin Paprotka
David Kessie
Helene Mehling
Jan Potempa
Knut Ohlsen
Martin J Fraunholz
Thomas Rudel
author_facet Kathrin Stelzner
Aziza Boyny
Tobias Hertlein
Aneta Sroka
Adriana Moldovan
Kerstin Paprotka
David Kessie
Helene Mehling
Jan Potempa
Knut Ohlsen
Martin J Fraunholz
Thomas Rudel
author_sort Kathrin Stelzner
title Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells.
title_short Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells.
title_full Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells.
title_fullStr Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells.
title_full_unstemmed Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells.
title_sort intracellular staphylococcus aureus employs the cysteine protease staphopain a to induce host cell death in epithelial cells.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/016ce96c8f4e4388a9897eb4c96ddd96
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