The interaction of Staphylococcus aureus bi-component γ-hemolysins and leucocidins with cells and lipid membranes

M Ferreras, F Höper, M Dalla Serra, DA Colin… - … et Biophysica Acta (BBA …, 1998 - Elsevier
M Ferreras, F Höper, M Dalla Serra, DA Colin, G Prévost, G Menestrina
Biochimica et Biophysica Acta (BBA)-Biomembranes, 1998Elsevier
Staphylococcus aureus γ-hemolysins (H1gA, H1gB and HlgC) and Panton-Valentine
leucocidins (LukS-PV and LukF-PV) are bi-component toxins forming a protein family with
some relationship to α-toxin. Active toxins are couples formed by taking one protein from
each of the two subfamilies of the S-components (LukS-PV, H1gA and HlgC) and the F-
components (LukF-PV and HlgB). We compared the mode of action of the six possible
couples on leukocytes, red blood cells and model lipid membranes. All couples were …
Staphylococcus aureus γ-hemolysins (H1gA, H1gB and HlgC) and Panton-Valentine leucocidins (LukS-PV and LukF-PV) are bi-component toxins forming a protein family with some relationship to α-toxin. Active toxins are couples formed by taking one protein from each of the two subfamilies of the S-components (LukS-PV, H1gA and HlgC) and the F-components (LukF-PV and HlgB). We compared the mode of action of the six possible couples on leukocytes, red blood cells and model lipid membranes. All couples were leucotoxic on human monocytes, whereas only four couples (H1gA+H1gB, H1gC+H1gB, LukS-PV+H1gB and H1gA+LukF-PV) were hemolytic. Toxins H1gA+H1gB and H1gC+H1gB were also able to induce permeabilisation of model membranes by forming pores via oligomerisation. The presence of membrane-bound aggregates, the smallest and most abundant of which had molecular weight and properties similar to that formed by α-toxin, was detected by SDS-PAGE. By infrared spectroscopy in the attenuated total reflection configuration (FTIR-ATR), the secondary structure of both components and of the aggregate were determined to be predominantly β-sheet and turn with small variations among different toxins. Polarisation experiments indicated that the structure of the membrane complex was compatible with the formation of a β-barrel oriented perpendicularly to the plane of the membrane, similar to that of porins. The couple LukS-PV+LukF-PV was leucotoxic, but not hemolytic. When challenged against model membranes it was able to bind to the lipid vesicles and to form the aggregate with the β-barrel structure, but not to increase calcein permeability. Thus, the pore-forming effect correlated with the hemolytic, but not with the complete leucotoxic activity of these toxins, suggesting that other mechanisms, like the interaction with endogenous cell proteins, might also play a role in their pathogenic action.
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