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Antimicrobial Agents and Chemotherapy, August 2000, p. 2154-2159, Vol. 44, No. 8
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Saccharomicins, Novel Heptadecaglycoside Antibiotics Produced by Saccharothrix espanaensis: Antibacterial and Mechanistic Activities

M. P. Singh,* P. J. Petersen, W. J. Weiss, F. Kong, and M. Greenstein

Infectious Diseases Section, Wyeth-Ayerst Research, Pearl River, New York 10965

Received 18 November 1999/Returned for modification 12 March 2000/Accepted 12 May 2000

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 µg/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 Ca2+ or Mg2+, but activity against gram-negative bacteria was substantially reduced.

* Corresponding author. Mailing address: Wyeth-Ayerst Research, 401 N. Middletown Rd., Pearl River, NY 10965. Phone: (914) 732-4869. Fax: (914) 732-5687. E-mail: singhm{at}war.wyeth.com.

Antimicrobial Agents and Chemotherapy, August 2000, p. 2154-2159, Vol. 44, No. 8
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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