Intracellular persistence of Staphylococcus aureus in endothelial cells is promoted by the absence of phenol-soluble modulins / Anke Siegmund, Muhammad Awais Afzal, Felix Tetzlaff, Daniela Keinhörster, Fabio Gratani, Kerstin Paprotka, Martin Westermann, Sandor Nietzsche, Christiane Wolz, Martin Fraunholz, Christian A. Hübner, Bettina Löffler & Lorena Tuchscherr

Abstract: A large proportion of clinical S. aureus isolates that carry an inactive Agr system are associated with persistent infection that is difficult to treat. Once S. aureus is inside the bloodstream, it can cross the endothelial barrier and invade almost every organ in the human body. Endothelial cells can either be lysed by this pathogen or they serve as a niche for its intracellular long-term survival. Following phagocytosis, several vesicles such as phagosomes and autophagosomes, target intracellular S. aureus for elimination. S. aureus can escape from these vesicles into the host cytoplasm through the activation of phenol-soluble modulins (PSMs) αβ. Thereafter, it replicates and lyses the host cell to disseminate to adjacent tissues. Herein we demonstrate that staphylococcal strains which lack the expression of PSMs employ an alternative pathway to better persist within endothelial cells. The intracellular survival of S. aureus is associated with the co-localization of the autophagy marker LC3. In cell culture infection models, we found that the absence of psmαβ decreased the host cell lysis and increased staphylococcal long-term survival. This study explains the positive selection of agr-negative strains that lack the expression of psmαβ in chronic infection due to their advantage in surviving and evading the clearance system of the host. Keywords: Staphylococcus aureusintracellular persistencephenol-soluble modulinslc3-vesicleschronic infections

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Persons: Siegmund, Anke [Author]; Afzal, Muhammad Awais [Author]; Tetzlaff, Felix [Author]; Keinhörster, Daniela [Author]; Gratani, Fabio Lino [Author]; Paprotka, Kerstin [Author]; Westermann, Martin [Author]; Nietzsche, Sandor [Author]; Wolz, Christiane [Author]; Fraunholz, Martin [Author]; Hübner, Christian [Author]; Löffler, Bettina [Author]; Tuchscherr, Lorena [Author]
Format: eArticle
Publication:12 Apr 2021
Part of:Virulence 12(2021,1) Artikel-Nummer 2818, 14 Seiten