The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity
2012 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 80, no 5, 1670-1680 p.Article in journal (Refereed) Published
Increased microvascular permeability is a hallmark of sepsis and septic shock. Intestinal mucosal dysfunction may allow translocation of bacteria and their products, thereby promoting sepsis and inflammation. Although Staphylococcus aureus alpha-toxin significantly contributes to sepsis and perturbs the endothelial barrier function, little is known about possible effects of S. aureus alpha-toxin on human epithelial barrier functions. We hypothesize that S. aureus alpha-toxin in the blood can impair the intestinal epithelial barrier and thereby facilitate the translocation of luminal bacteria into the blood, which may in turn aggravate a septic condition. Here, we showed that staphylococcal alpha-toxin disrupts the barrier integrity of human intestinal epithelial Caco-2 cells as evidenced by decreased transepithelial electrical resistance (TER) and reduced cellular levels of junctional proteins, such as ZO-1, ZO-3, and E-cadherin. The Caco-2 cells also responded to alpha-toxin with an elevated cytosolic calcium ion concentration ([Ca2+](i)), elicited primarily by calcium influx from the extracellular environment, as well as with a significant reduction in TER, which was modulated by intracellular calcium chelation. Moreover, a significantly larger reduction in TER and amounts of the junctional proteins, viz., ZO-3 and occludin, was achieved by basolateral than by apical application of the alpha-toxin. These experimental findings thus support the hypothesis that free staphylococcal alpha-toxin in the bloodstream may cause intestinal epithelial barrier dysfunction and further aggravate the septic condition by promoting the release of intestinal bacteria into the underlying tissues and the blood.
Place, publisher, year, edition, pages
2012. Vol. 80, no 5, 1670-1680 p.
Gut-Derived Sepsis, Bacterial Translocation, Calcium, Permeability, Impact, Hemolysin, Carriage, Pore, Enterotoxin, Infections
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:kth:diva-95242DOI: 10.1128/IAI.00001-12ISI: 000302791100006ScopusID: 2-s2.0-84861177209OAI: oai:DiVA.org:kth-95242DiVA: diva2:528090
FunderSwedish Research Council, 2007-3483 2009-6649 2010-3045
QC 201205242012-05-242012-05-212012-05-24Bibliographically approved