Metabolic Cross-talk Between Human Bronchial Epithelial Cells and Internalized Staphylococcus aureus as a Driver for Infection

Staphylococcus aureus is infamous for causing recurrent infections of the human respiratory tract. This is a consequence of its ability to adapt to different niches, including the intracellular milieu of lung epithelial cells. To understand the dynamic interplay between epithelial cells and the intr...

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Published inMolecular & cellular proteomics Vol. 18; no. 5; p. 892
Main Authors Palma Medina, Laura M, Becker, Ann-Kristin, Michalik, Stephan, Yedavally, Harita, Raineri, Elisa J M, Hildebrandt, Petra, Gesell Salazar, Manuela, Surmann, Kristin, Pförtner, Henrike, Mekonnen, Solomon A, Salvati, Anna, Kaderali, Lars, van Dijl, Jan Maarten, Völker, Uwe
Format Journal Article
LanguageEnglish
Published United States 01.05.2019
Subjects
Infectious disease
Energy metabolism
in vivo proteomics
bronchial epithelial cells
Bacteria
persister
Autophagy
population heterogeneity
Staphylococcus aureus
Apoptosis
Host-Pathogen Interaction
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Summary:Staphylococcus aureus is infamous for causing recurrent infections of the human respiratory tract. This is a consequence of its ability to adapt to different niches, including the intracellular milieu of lung epithelial cells. To understand the dynamic interplay between epithelial cells and the intracellular pathogen, we dissected their interactions over 4 days by mass spectrometry. Additionally, we investigated the dynamics of infection through live cell imaging, immunofluorescence and electron microscopy. The results highlight a major role of often overlooked temporal changes in the bacterial and host metabolism, triggered by fierce competition over limited resources. Remarkably, replicating bacteria reside predominantly within membrane-enclosed compartments and induce apoptosis of the host within ∼24 h post infection. Surviving infected host cells carry a subpopulation of non-replicating bacteria in the cytoplasm that persists. Altogether, we conclude that, besides the production of virulence factors by bacteria, it is the way in which intracellular resources are used, and how host and intracellular bacteria subsequently adapt to each other that determines the ultimate outcome of the infectious process.
ISSN:1535-9484