The mode of action of SA-FF22, a lantibiotic isolated from Streptococcus pyogenes strain FF22.
SA-FF22 is a lanthionine-containing bacteriocidal peptide isolated from Streptococcus pyogenes strain FF22. The peptide interacts closely with non-energised artificial phospholipid vesicles, as evidenced by a 'blue shift' in the fluorescent emissions associated with a tryptophan residue within the peptide sequence. Furthermore, SA-FF22 induced efflux of radiolabelled amino acids from artificially energised cytoplasmic membrane vesicles and arrested uptake of amino acids by intact cells. By measuring the decrease in membrane potential of both starved and energised SA-FF22-treated cells, and through the use of artificial planar membranes, a potential of approximately 100 mV was deduced as the minimum required to induce pore formation by SA-FF22. This threshold potential is independent of the orientation of the applied voltage (i.e. trans or cis orientations are equally effective). Single channel conductance measurements suggested that the pores formed by SA-FF22 are relatively unstable, short-lived and approximately 0.5-0.6 nm in diameter. This is somewhat smaller than those of the previously described, pore-forming lantibiotics and should not allow significant efflux of large molecules such as ATP. Thus, death of affected cells seems to result from membrane-potential disruption and subsequent exhaustion of the cells.
Jack
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Institut für Medizinische Mikrobiologie und Immunologie, Universität Bonn.
Benz
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R
Tagg
J
J
Sahl
H G
HG
D000409:Alanine / Q000031:analogs & derivatives / Q000032:analysis; D000596:Amino Acids / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000378:metabolism*; D001430:Bacteriocins; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D010455:Peptides; D010743:Phospholipids; D013050:Spectrometry, Fluorescence; D013291:Streptococcus / Q000187:drug effects / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000378:metabolism*; D013440:Sulfides
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides; D010743:Phospholipids; D013440:Sulfides; C016887:A-FF22; C001520:lanthionine; D000409:Alanine