Cluster-forming property correlated with hemolytic activity by staphylococcal γ-hemolysin transmembrane pores

Abstract

Two-component cytolysin Pore-forming toxin Cluster formation Transmission electron microscopy Image analysis a b s t r a c t Staphylococcal c-hemolysin (Hlg) is a pore-forming toxin consisting of two separate components, LukF (34 kDa) and Hlg2 (32 kDa). Here we show that Hlg pores aggregate and form clusters on human erythrocyte membranes in association with increasing hemolytic activity. Quantitative analysis using transmission electron microscopy and image processing revealed that the formation of single pores and clusters is related to the release of potassium ions and of hemoglobin from erythrocytes, respectively. This is the first study to suggest a novel and unique property which can facilitate hemolysis by the cluster formation of Hlg pores.

Metastable HIV-1 Surface Protein Env Sensitizes Cell Membranes to Transformation and Poration by Dual-Acting Virucidal Entry Inhibitors

“…Studies focused on characterizing bacterial pore-forming toxins have also described the distinction between poration and cytotoxicity/cytolysis. − In these studies, bulkier proteins (e.g., hemoglobin) and polydextrans were used as nonleaking size controls, while smaller molecules leaked freely, much as calcein did in our observations. The literature on repair from pore-forming toxins and mechanical rupture also argues that pores and membrane disruptions can be repaired if not too extreme, which may explain our observations in the “low-Env” cell populations.…”

The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus

“…Given data that demonstrate saturable and specific binding kinetics on target host cells, it seems unlikely that gammahemolysin recognizes lipid motifs exclusively to cause cell lysis. However, enrichment of certain lipids in raft-like microdomains or under artificial conditions may allow for an enhanced poreforming capacity in a manner that is independent of receptor recognition (191,258). In fact, synthetic vesicles composed of defined lipids can lead to HlgAB-mediated pore formation in the absence of a protein receptor or GM1 (242).…”

Pathogenic Pore-Forming Proteins: Function and Host Response

“…This difference in stochiometry translates into differences in pore diameter, which range from 1.5-2 nm for aerolysin to >30 nm for CDCs (Hotze and Tweten, 2012;Iacovache et al, 2010). Interestingly, pores formed by PFTs may arrange into higher-order assemblies on target cell membranes leading to larger lesions (Tomita et al, 2011).…”