Staphylococcus aureus escapes more efficiently from the phagosome of a cystic fibrosis bronchial epithelial cell line than from its normal counterpart.
Staphylococcus aureus is frequently the initial bacterium isolated from young cystic fibrosis (CF) patients, and yet its role in CF disease progression has not been determined. Recent data from our lab demonstrates that S. aureus can invade and replicate within the CF tracheal epithelial cell line (CFT-1). Here we describe the finding that the fate of internalized S. aureus in CFT-1 cells differs from its complemented counterpart (LCFSN). S. aureus strain RN6390 was able to replicate within the mutant CFT-1 cells after invasion but not in the complemented LCFSN cells. At 1 h postinvasion, S. aureus containing vesicles within both cell lines acquired vacuolar-ATPase, lysosomal markers LAMP 1 and 2, and the lysomotrophic dye LysoTracker to a similar degree. However, at 4 h postinvasion, the percentage of S. aureus within CFT-1 cells associated with these markers decreased significantly compared to LCFSN, where the association approached 100%. Transmission electron microscopic analysis revealed that the majority of bacteria within CFT-1 cells were free in the cytosol at 4 h after invasion, whereas most S. aureus bacteria internalized by LCFSN cells remained within vesicles. These results demonstrate a fundamental difference in the fate of live S. aureus after invasion of CFT-1 versus LCFSN cell lines and may explain the propensity of S. aureus to cause chronic lung infection in CF patients.
Jarry
Todd M
TM
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
Cheung
Ambrose L
AL
D001422:Bacterial Adhesion; D001980:Bronchi / Q000382:microbiology*; D002460:Cell Line; D003550:Cystic Fibrosis / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D011992:Endosomes / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000032:analysis; D008854:Microscopy, Electron; D010588:Phagosomes / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D025262:Vacuolar Proton-Translocating ATPases; C505032:CFTR protein, human; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C497811:LAMP2 protein, human