Saccharomicins, novel heptadecaglycoside antibiotics produced by Saccharothrix espanaensis: antibacterial and mechanistic activities.
Saccharomicins A and B, two new heptadecaglycoside antibiotics, were isolated from the fermentation broth of the rare actinomycete Saccharothrix espanaensis. They represent a novel class of bactericidal antibiotics that are active both in vitro and in vivo against bacteria and yeast (MICs: Staphylococcus aureus, <0.12 to 0. 5; vancomycin-resistant enterococci, 0.25 to 16; gram-negative bacteria, 0.25 to >128; and yeast, >128 microg/ml), including multiply resistant strains. Saccharomicins protected mice from lethal challenges by staphylococci (subcutaneous 50% effective dose range of 0.06 to 2.6 mg/kg of body weight, depending on the S. aureus strain). The 50% lethal dose by the subcutaneous route was 16 mg/kg. Mechanistic studies with Escherichia coli imp and Bacillus subtilis suggested complete, nonspecific inhibition of DNA, RNA, and protein biosynthesis within 10 min of drug treatment. Microscopic examination of drug-treated cells also suggested cell lysis. These data are consistent with a strong membrane-disruptive activity. The antibacterial activities of the saccharomicins against gram-positive bacteria were unaffected by the presence of Ca(2+) or Mg(2+), but activity against gram-negative bacteria was substantially reduced.
Singh
M P
MP
Infectious Diseases Section, Wyeth-Ayerst Research, Pearl River, New York 10965, USA. singhm@war.wyeth.com
Petersen
P J
PJ
Weiss
W J
WJ
Kong
F
F
Greenstein
M
M
D000192:Actinomycetales / Q000737:chemistry*; D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002240:Carbohydrate Sequence; D002412:Cations / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000517:prevention & control; D006461:Hemolysis; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D013210:Staphylococcus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002412:Cations; D011506:Proteins; D014640:Vancomycin; D004247:DNA