Intracellular persistence of Staphylococcus aureus in endothelial cells is promoted by the absence of phenol-soluble modulins

Virulence

Felix Tetzlaff¹  Muhammad Awais Afzal¹  Christian A. Hübner¹  Christiane Wolz²  Daniela Keinhörster²  Fabio Gratani²  Martin Westermann³  Bettina Löffler³  Anke Siegmund³  Lorena Tuchscherr³  Sandor Nietzsche³  Kerstin Paprotka⁴  Martin Fraunholz⁴ 

[1] Institute of Human Genetics, Jena University Hospital;Interfaculty Institute for Microbiology and Infection Medicine Tübingen;Jena University Hospital;University of Würzburg;

关键词: staphylococcus aureus;    intracellular persistence;    phenol-soluble modulins;    lc3-vesicles;    chronic infections;   

DOI  :  10.1080/21505594.2021.1910455

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown