A study on the mechanism of action of sceptrin, an antimicrobial agent isolated from the South Pacific sponge Agelas mauritiana.
The mechanism of action of sceptrin, an antimicrobial agent isolated from the sponge Agelas mauritiana, was investigated. Sceptrin has been reported to exhibit antibacterial and antifungal activities. In our studies, sceptrin demonstrated a bacteriostatic rather than bactericidal effect on exponentially growing Escherichia coli cells at the MIC. Under these conditions, the culture produced chains of cells, and incorporation of radio-labelled precursors into DNA, protein, and cell wall was unaffected, whereas incorporation of 3H-uridine into RNA was slightly inhibited. At concentrations higher than the MIC, sceptrin was bactericidal, inhibited the incorporation of all radiolabelled precursors, and induced the formation of unusual spheroplasts. Peptidoglycan turnover in E. coli appeared to be stimulated by sceptrin as demonstrated by a release of diaminopimelic acid-containing high molecular weight material. Subsequent studies of the release of potassium ions from E. coli and the lysis of red blood cells suggested that sceptrin disrupts the cell membranes of both prokaryotic and eukaryotic cells. It is proposed that spheroplasts formation may reflect a cell wall effect that occurs subsequent to membrane damage.
Bernan
V S
VS
American Cyanamid Company, Medical Research Division, Pearl River, NY 10965.
Roll
D M
DM
Ireland
C M
CM
Greenstein
M
M
Maiese
W M
WM
Steinberg
D A
DA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D003470:Culture Media; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D011188:Potassium / Q000378:metabolism; D011758:Pyrroles / Q000302:isolation & purification / Q000494:pharmacology*; D012756:Sheep
D000900:Anti-Bacterial Agents; D003470:Culture Media; D011758:Pyrroles; C077210:sceptrin; D010400:Penicillin G; D011188:Potassium