The staphylococcal pore-forming leukotoxins open Ca2+ channels in the membrane of human polymorphonuclear neutrophils.
The ability of leukotoxins secreted by Staphylococcus aureus to modify the permeability of the membrane of human polymorphonuclear neutrophils has been studied by spectrofluorometry and appropriate fluorescent probes. This family of bicomponent leukotoxins is constituted by, at least, three pairs of proteins: LukS-PV/LukF-PV, HlgA/HlgB, HlgC/HlgB. After binding of both components to the membrane, each pair induces influxes of divalent cations and ethidium in polymorphonuclear neutrophils, although with different intensities. The influx of divalent cations appears sooner than the influx of ethidium. The pathway for divalent cations is not permeable to monovalent cations (Na+, K+, ethidium+) and is blocked by Ca2+ channel inhibitors that do not block the fluxes of ethidium and monovalent cations. It is concluded that the leukotoxins bind to a receptor linked to a divalent cation-selective channel or to the channel itself which is activated. Then, the leukotoxins open a second pathway by insertion into the membrane and subsequent formation of aspecific pores allowing an influx of ethidium.
Staali
L
L
Laboratoire de Toxinologie et d'Antibiologie Bactériennes, Institut de Bactériologie, Université Louis Pasteur, Strasbourg, France.
Monteil
H
H
Colin
D A
DA
D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002412:Cations; D002462:Cell Membrane / Q000187:drug effects; D005260:Female; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006801:Humans; D007956:Leukocidins / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013211:Staphylococcus aureus / Q000378:metabolism*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002412:Cations; D006460:Hemolysin Proteins; D007956:Leukocidins; C037956:gamma-hemolysin, Staphylococcus aureus; C108483:leukocidin S-component protein, Staphylococcus; C074300:LukF protein, Staphylococcus aureus