Cytoplasmic replication of Staphylococcus aureus upon phagosomal escape triggered by phenol-soluble modulin α
Magdalena Grosz1,2, Julia Kolter1, Kerstin Paprotka1, Ann-Cathrin Winkler1, Daniel Schäfer2, Som Subra Chatterjee3, Tobias Geiger4, Christiane Wolz4, Knut Ohlsen5, Michael Otto3, Thomas Rudel1, Bhanu Sinha2,6,† andMartin Fraunholz1,†,*
Article first published online: 12 NOV 2013
DOI: 10.1111/cmi.12233
© 2013 John Wiley & Sons Ltd
Issue Cellular Microbiology
Cellular Microbiology
Volume 16, Issue 4, pages 451–465, April 2014
Additional Information(Show All)
How to CiteAuthor InformationPublication HistoryFunding Information
SEARCH
Search Scope
Search StringSearch
Advanced >Saved Searches >
ARTICLE TOOLS
Get PDF (480K)
Save to My Profile
E-mail Link to this Article
Export Citation for this Article
Get Citation Alerts
Request Permissions
More Sharing ServicesShare|Share on citeulikeShare on facebookShare on deliciousShare on www.mendeley.comShare on twitter
Abstract
Article
References
Supporting Information
Cited By
View Full Article with Supporting Information (HTML) Enhanced Article (HTML) Get PDF (480K)
Summary
Staphylococcus aureus is a Gram-positive human pathogen that is readily internalized by professional phagocytes such as macrophages and neutrophils but also by non-professional phagocytes such as epithelial or endothelial cells. Intracellular bacteria have been proposed to play a role in evasion of the innate immune system and may also lead to dissemination within migrating phagocytes. Further, S. aureus efficiently lyses host cells with a battery of cytolytic toxins. Recently, phenol-soluble modulins (PSM) have been identified to comprise a genus-specific family of cytolytic peptides. Of these the PSMα peptides have been implicated in killing polymorphonuclear leucocytes after phagocytosis. We questioned if the peptides were active in destroying endosomal membranes to avoid lysosomal killing of the pathogen and monitored integrity of infected host cell endosomes by measuring the acidity of the intracellular bacterial microenvironment via flow cytometry and by a reporter recruitment technique. Isogenic mutants of the methicillin-resistant S. aureus (MRSA) strains USA300 LAC, USA400 MW2 as well as the strongly cytolytic methicillin-sensitive strain 6850 were compared with their respective wild type strains. In all three genetic backgrounds, PSMα mutants were unable to escape from phagosomes in non-professional (293, HeLa, EAhy.926) and professional phagocytes (THP-1), whereas mutants in PSMβ and δ-toxin as well as β-toxin, phosphatidyl inositol-dependent phospholipase C and Panton Valentine leucotoxin escaped with efficiencies of the parental strains. S. aureus replicated intracellularly only in presence of a functional PSMα operon thereby illustrating that bacteria grow in the host cell cytoplasm upon phagosomal escape.