Proteomics

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Major determinants of airway epithelial cell sensitivity to S. aureus alpha-toxin: Disposition of toxin heptamers by extracellular vesicle formation and lysosomal degradation


ABSTRACT: Alpha-toxin is a major virulence factor of Staphylococcus aureus and plays an important role in S. aureus-induced pneumonia. Different sensitivities toward the toxin of various host cell types have been observed. In this study we investigated internalization of pore-containing areas of the plasma membrane in these cell types as well as potential pathways for heptamer degradation (lysosomal, proteasomal) or disposal (formation of exosomes/microvesicles containing toxin pores). Comparisons of heptamer degradation rates under inhibition of lysosomal or proteasomal degradation revealed that an important route of heptamer degradation at least in S9 cells seemed to be the lysosomal pathway while proteasomal degradation did not seem to be relevant. Exosomes prepared from culture supernatants of toxin-exposed S9 cells, contained alpha-toxin as well as low amounts of marker proteins of exosomes and microvesicles. These results indicate that the ability of lysosomal degradation of internalized toxin heptamers may be the most important determinant of toxin-resistance of some types of airway epithelial cells. In this study, we compared the proteomes of rHla treated (90 min), 8 h starvation and, 48 h starvation for the S9 cells by mass spectrometry.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, Epithelial Cell

SUBMITTER: christian hentschker  

LAB HEAD: Jan-Peter Hildebrandt

PROVIDER: PXD023678 | Pride | 2021-04-20

REPOSITORIES: Pride

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Publications

Major Determinants of Airway Epithelial Cell Sensitivity to <i>S. aureus</i> Alpha-Toxin: Disposal of Toxin Heptamers by Extracellular Vesicle Formation and Lysosomal Degradation.

Möller Nils N   Ziesemer Sabine S   Hentschker Christian C   Völker Uwe U   Hildebrandt Jan-Peter JP  

Toxins 20210224 3


Alpha-toxin is a major virulence factor of <i>Staphylococcus aureus</i>. Monomer binding to host cell membranes results in the formation of heptameric transmembrane pores. Among human model airway epithelial cell lines, A549 cells were most sensitive toward the toxin followed by 16HBE14o<sup>-</sup> and S9 cells. In this study we investigated the processes of internalization of pore-containing plasma membrane areas as well as potential pathways for heptamer degradation (lysosomal, proteasomal) o  ...[more]

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