In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-2), p. e1009874-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009874
DOI:
10.1371/journal.ppat.1009874.g001
DOI:
10.1371/journal.ppat.1009874.g002
DOI:
10.1371/journal.ppat.1009874.g003
DOI:
10.1371/journal.ppat.1009874.g004
DOI:
10.1371/journal.ppat.1009874.g005
DOI:
10.1371/journal.ppat.1009874.g006
DOI:
10.1371/journal.ppat.1009874.g007
DOI:
10.1371/journal.ppat.1009874.s001
DOI:
10.1371/journal.ppat.1009874.s002
DOI:
10.1371/journal.ppat.1009874.s003
DOI:
10.1371/journal.ppat.1009874.s004
DOI:
10.1371/journal.ppat.1009874.s005
DOI:
10.1371/journal.ppat.1009874.s006
DOI:
10.1371/journal.ppat.1009874.s007
DOI:
10.1371/journal.ppat.1009874.s008
DOI:
10.1371/journal.ppat.1009874.s009
DOI:
10.1371/journal.ppat.1009874.s010
DOI:
10.1371/journal.ppat.1009874.s011
DOI:
10.1371/journal.ppat.1009874.s012
DOI:
10.1371/journal.ppat.1009874.s013
DOI:
10.1371/journal.ppat.1009874.s014
DOI:
10.1371/journal.ppat.1009874.s015
DOI:
10.1371/journal.ppat.1009874.r001
DOI:
10.1371/journal.ppat.1009874.r002
DOI:
10.1371/journal.ppat.1009874.r003
DOI:
10.1371/journal.ppat.1009874.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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