Open AccessIntracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells
Author(s) -
Kathrin Stelzner,
Aziza Boyny,
Tobias Hertlein,
Aneta Sroka,
Adriana Moldovan,
Kerstin Paprotka,
David Komla Kessie,
Helene Mehling,
Jan Potempa,
Knut Ohlsen,
Martin Fraunholz,
Thomas Rudel
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009874
Subject(s) - intracellular , phagosome , staphylococcus aureus , biology , microbiology and biotechnology , intracellular parasite , internalization , programmed cell death , phagocytic cell , cytotoxic t cell , cysteine protease , cell , phagocytosis , protease , apoptosis , bacteria , in vitro , biochemistry , genetics , enzyme
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.