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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2021
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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) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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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 |
work_keys_str_mv |
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