Staphylococcus aureus, Pore-forming

In reconstitution experiments, the self-assembly of the pore-forming protein a-hemolysin of Staphylococcus aureus (aHL) [181-183] was examined in plain and S-layer-supported lipid bilayers. Staphylococcal aHL formed lytic pores when added to the lipid-exposed side of the DPhPC bilayer with or without an attached S-layer from B coagulans E38/vl. The assembly of aHL pores was slower at S-layer-supported compared to unsupported folded membranes. No assembly could be detected upon adding aHL monomers to the S-layer face of the composite membrane. Therefore, the intrinsic molecular sieving properties of the S-layer lattice did not allow passage of aHL monomers through the S-layer pores to the lipid bilayer [142]. 

Bacterial pore-forming proteins, such as oc-hemolysin, secreted by Staphylococcus aureus can be modified so that pore formation is activated by chemical, biochemical, or physical triggers. Such hemolysins, when targeted to tumors, could increase tumor permeability, and hence susceptibility to various cytotoxic drugs (78). 

Raja, S. M., Rawat, S. S., Chattopadhyay, A. and Lala, A. K. 1999. Localization and Environment of Tryptophans in Soluble and Membrane-Bound States of a Pore-Forming Toxin from Staphylococcus aureus. Biophysical Journal 76, 1469-1479. 

This type of antiparallel packing of /3 -strands in integral membrane proteins has also been observed in hemolysin. Hemolysin is a heptameric pore forming protein from Staphylococcus aureus, where each of the subunits contributes two antiparallel /3-strands to the transmembrane segment creating a 14 stranded barrel. 

E. coll was also engineered to produce Staphylococcus aureus a-hanolysin (SAH) (Jean et al., 2014), a pore-forming protein/toxin that has been recently found to be naturally secreted in a fully functional form in E. coli and to aggressively kill mammalian cancer cells (Swofford et al., 2014). Microbial synthesized SAH was found to increase necrotic tissue and quickly reduce tumor volume (Jean et al., 2014) by creating pores that disrupt and destroy mammalian cellular membranes, as well as induce cell swelling and lysis (Swofford et al., 2014). 

Figure 1. Schematic representation of the steps involved in the binding and membrane pore formation by Staphylococcus aureus a-toxin (adapted from Walker et al., 1992). (1) Monomeric form of water soluble a-toxin consists of a N-terminal domain and a C-terminal domain that are separated by a glycine-rich loop. (2) The toxin binds to membrane in its monomeric form. (3) A non-lytic oligomer is formed consisting of up to six subunits. (4) The subunits then penetrate further to form the lytic pore.

---