Saccharomicins, novel heptadecaglycoside antibiotics produced by Saccharothrix espanaensis: Antibacterial and mechanistic activities

Saccharomicins A and B, two new heptadecaglycoside antibiotics, were isolat ed front the fermentation broth of the rare actinomycete Saccharothrix espa naensis, They represent a novel class of bactericidal antibiotics that are active both in vitro and in vivo against bacteria and yeast (MICs: Stapyloc occus aureus, <0.12 to 0.5; vancomycin-resistant enterococci, 0.25 to 16; g ram-negative bacteria, 0.25 to >128; and yeast, >128 mu g/ml), including mu ltiply resistant strains. Saccharomicins protected mice from lethal challen ges 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 do se by the subcutaneous route was 16 mg/kg, Mechanistic studies with Escheri chia coli imp and Bacillus subtilis suggested complete, nonspecific inhibit ion of DNA, RNA, and protein biosynthesis within 10 min of drug treatment. Microscopic examination of drug-treated cells also suggested cell ISE;is. T hese data are consistent with a strong membrane disruptive activity, The an tibacterial activities of the saccharomicins against gram-positive bacteria were unaffected by the presence of Ca2+ or Mg2+, but activity against gram negative bacteria was substantially reduced.