Effects of Staphylococcus aureus-hemolysin A on calcium signalling in immortalized human airway epithelial cells

Eichstaedt, Stefanie; Gäbler, Karoline; Below, Sabine; Müller, Christian; Köhler, Christian; Engelmann, Susanne; Hildebrandt, Petra; Völker, Uwe; Hecker, Michael; Hildebrandt, Jan‐Peter

doi:10.1016/j.ceca.2008.09.001

Cited by 51 publications

(70 citation statements)

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“…Similar to our results, S. aureus alpha-toxin elevated [Ca 2ϩ ] i in immortalized human airway epithelial cells (S9) within 5 min, which has been assumed to result in a barrier dysfunction (13,19,53). The [Ca 2ϩ ] i elevation occurred earlier than that in our study, which could reflect differences in plasma membrane composition and consequent pore-forming capacity of the alpha-toxin.…”

Section: Discussionsupporting

confidence: 64%

“…Alterations of cytosolic free Ca 2ϩ concentration are the way to regulate cellular responses (26,56). For example, S. aureus alphatoxin has been shown to induce a rise of cytosolic free Ca 2ϩ in human airway epithelial cells (13) and endothelial cells (46). In cultured Caco-2 cells, Clostridium perfringens enterotoxin (CPE) (36) and Aeromonas sobria hemolysin (ASH) increased cytosolic free Ca 2ϩ , which was assumed to contribute to the cytopathic effects (50).…”

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confidence: 99%

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The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity

et al. 2012

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ABSTRACTIncreased 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. AlthoughStaphylococcus aureusalpha-toxin significantly contributes to sepsis and perturbs the endothelial barrier function, little is known about possible effects ofS. aureusalpha-toxin on human epithelial barrier functions. We hypothesize thatS. aureusalpha-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.

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Section: Discussionsupporting

confidence: 64%

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confidence: 99%

The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity

et al. 2012

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“…The staphylococcal toxin, alpha-hemolysin (Hla), was reported to induce apoptosis upon intracellular staphylococcal infection (37). The apoptotic pathways affected by S. aureus appear to depend on the strain and host cell type used, and several studies argue for or against its employment of molecules such as caspases (38)(39)(40)(41) or calcium (42) to induce apoptosis in epithelial cells. On the other hand, as seen for many other bacteria, S. aureus may also be able to block apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcal Esx Proteins Modulate Apoptosis and Release of Intracellular Staphylococcus aureus during Infection in Epithelial Cells

et al. 2014

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bThe opportunistic pathogen Staphylococcus aureus is one of the major causes of health care-associated infections. S. aureus is primarily an extracellular pathogen, but it was recently reported to invade and replicate in several host cell types. The ability of S. aureus to persist within cells has been implicated in resistance to antimicrobials and recurrent infections. However, few staphylococcal proteins that mediate intracellular survival have been identified. Here we examine if EsxA and EsxB, substrates of the ESAT-6-like secretion system (Ess), are important during intracellular S. aureus infection. The Esx proteins are required for staphylococcal virulence, but their functions during infection are unclear. While isogenic S. aureus esxA and esxB mutants were not defective for epithelial cell invasion in vitro, a significant increase in early/late apoptosis was observed in esxA mutant-infected cells compared to wild-type-infected cells. Impeding secretion of EsxA by deleting C-terminal residues of the protein also resulted in a significant increase of epithelial cell apoptosis. Furthermore, cells transfected with esxA showed an increased protection from apoptotic cell death. A double mutant lacking both EsxA and EsxB also induced increased apoptosis but, remarkably, was unable to escape from cells as efficiently as the single mutants or the wild type. Thus, using in vitro models of intracellular staphylococcal infection, we demonstrate that EsxA interferes with host cell apoptotic pathways and, together with EsxB, mediates the release of S. aureus from the host cell.

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“…This results in the formation of a barrel-shaped transmembrane pore with an inner diameter of ϳ1.4 nm at its narrowest site (18,37). The effective diameter of the pore may be even smaller, as indicator molecules such as acridine orange (265 g/mol), BCECF (ϳ600 g/mol), or Indo-1 (ϳ500 g/mol) do not leave the cells upon treatment with Hla (14,58). Many cell types release ATP (507 g/mol) to the external medium upon exposure to Hla (12,17,24,36,41,55,58,59), but it is not clear whether ATP exits the cells through Hla pores or through other pathways.…”

mentioning

confidence: 99%

“…Many cell types release ATP (507 g/mol) to the external medium upon exposure to Hla (12,17,24,36,41,55,58,59), but it is not clear whether ATP exits the cells through Hla pores or through other pathways. Furthermore, whether the Hla pore is directly permeable to mono-or divalent cations (Na ϩ , Ca 2ϩ ) has been often discussed, but experimental evidence is scarce and in part controversial (2,14,27,31,50,56,58,59).…”

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confidence: 99%

Staphylococcus aureusα-toxin-mediated cation entry depolarizes membrane potential and activates p38 MAP kinase in airway epithelial cells

Eiffler

Behnke

Ziesemer

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Effects of Staphylococcus aureus-hemolysin A on calcium signalling in immortalized human airway epithelial cells

Cited by 51 publications

References 48 publications

The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity

The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity

Staphylococcal Esx Proteins Modulate Apoptosis and Release of Intracellular Staphylococcus aureus during Infection in Epithelial Cells

Staphylococcus aureusα-toxin-mediated cation entry depolarizes membrane potential and activates p38 MAP kinase in airway epithelial cells

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