A comparative study of α-Hemolysin and Jacalin that influence mammalian cell signaling

Abstract

To overcome host cell defense and for pathogenesis, pathogenic bacteria secrete soluble factors to interact and interfere with essential host systems. Most of these soluble factors are known as pore forming toxins and likely to be the primary virulence factors. They modulate host cell signaling or damage host cell membranes by pore formation upon binding to susceptible target cells. Staphylococcus aureus bacteria secrete a soluble pore forming toxin “α-hemolysin”, which follows a multi-step oligomerization process to assemble into a heptameric functional pore on the target or host cell membrane after binding. Membrane binding of α-HL and its oligomerization into heptameric pore either modulates host cell signaling or permeabilizes the target cells. Although α-HL binds to virtually all mammalian cells but also shows cell tropism dependent differential membrane recognition. Differential membrane recognition compels us to believe that α-HL may bind to specific receptor(s) on susceptible host membrane for its action. But the eukaryotic cell micro-domain (lipid raft/caveolae) specific receptor(s) or molecules that aid susceptibility dependent membrane recognition and assembly of α-HL was not ascertained. Here we studied the molecular basis of differential membrane recognition domain of α-HL and how it exploits eukaryotic membrane receptor for assembly and modulation of mammalian cell signaling.