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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Cell+Microbiol
2014 ; 16
(4
): 451-65
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Cytoplasmic replication of Staphylococcus aureus upon phagosomal escape triggered
by phenol-soluble modulin ?
#MMPMID24164701
Grosz M
; Kolter J
; Paprotka K
; Winkler AC
; Schäfer D
; Chatterjee SS
; Geiger T
; Wolz C
; Ohlsen K
; Otto M
; Rudel T
; Sinha B
; Fraunholz M
Cell Microbiol
2014[Apr]; 16
(4
): 451-65
PMID24164701
show ga
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 PSM? 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, PSM? mutants were unable to escape from phagosomes in
non-professional (293, HeLa, EAhy.926) and professional phagocytes (THP-1),
whereas mutants in PSM? and ?-toxin as well as ?-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 PSM? operon thereby illustrating that bacteria grow
in the host cell cytoplasm upon phagosomal escape.