Staphylococcus Aureus Alpha-toxin Induces Actin Filament Remodeling in Human Airway Epithelial Model Cells.

Staphylococcus Aureus Alpha-toxin Induces Actin Filament Remodeling in Human Airway Epithelial Model Cells.

Am J Respir Cell Mol Biol. 2017 Nov 07;:

Authors: Ziesemer S, Eiffler I, Schönberg A, Müller C, Hochgräfe F, Beule AG, Hildebrandt JP

Abstract
Exposure of cultured human airway epithelial model cells (16HBE14o-, S9) to Staphylococcus aureus alpha-toxin (hemolysin A, Hla) induces changes in cell morphology and cell layer integrity which are due to the inability of the cells to maintain stable cell-cell or focal contacts and to properly organize their actin cytoskeleton. The aim of this study was to identify Hla-activated signaling pathways involved in regulating the phosphorylation level of the actin depolymerizing factor cofilin. We used recombinant wild-type Hla (rHla) as well as a variant of Hla (rHla-H35L) that is unable to form functional transmembrane pores to treat immortalized human airway epithelial cells (16HBE14o-, S9) as well as freshly isolated human nasal tissue. Our results indicate that rHla-mediated changes in cofilin phosphorylation require the formation of functional Hla-pores in the host cell membrane. Formation of functional transmembrane pores induced hypo-phosphorylation of cofilin at Ser3, which was mediated by rHla-induced attenuation of PAK- and LIMK activities. Because dephosphorylation of pSer3-cofilin results in activation of this actin depolymerizing factor, treatment of cells with rHla resulted in loss of actin stress fibers from the cells and destabilization of cell shape followed by the appearance of paracellular gaps in the cell layers. Activation of protein kinase A or activation of small GTPases (Rho, Rac, Cdc42) do not seem to be involved in this response.

PMID: 29111771 [PubMed - as supplied by publisher]

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