Pseudomonas aeruginosa quorum sensing molecule N-(3 oxododecanoyl)-l-homoserine lactone disrupts epithelial barrier integrity of Caco-2 cells.
Acyl-homoserine lactone (HSL) quorum sensing molecules play an important role in regulation of virulence gene expression in Pseudomonas aeruginosa. Here, we show that 3O-C(12)-HSL can disrupt barrier integrity in human epithelial Caco-2 cells as evidenced by decreased transepithelial electrical resistance (TER), increased paracellular flux, reduction in the expression and distribution of ZO-1 and occludin, and reorganization of F-actin. P. aeruginosa 3O-C(12)-HSL activate p38 and p42/44 kinases, and inhibition of these kinases partly prevented 3O-C(12)-HSL-induced changes in TER, paracellular flux and expression of occludin and ZO-1. These findings demonstrate that P. aeruginosa 3O-C(12)-HSL can modulate tight junction integrity of Caco-2 cells.
Vikström
Elena
E
Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Linköping University, SE-58185 Linköping, Sweden. elevi@imk.liu.se
Tafazoli
Farideh
F
Magnusson
Karl-Eric
KE
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D018938:Caco-2 Cells; D002448:Cell Adhesion; D049109:Cell Proliferation; D003911:Dextrans / Q000494:pharmacology; D017097:Electric Impedance; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000737:chemistry*; D053038:Quorum Sensing; D062826:Zonula Occludens-1 Protein
D000199:Actins; D003911:Dextrans; D008565:Membrane Proteins; C109860:N-(3-oxododecanoyl)homoserine lactone; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D006714:Homoserine; D020928:Mitogen-Activated Protein Kinases; D015107:4-Butyrolactone