Mechanistic studies and biological activity of bioxalomycin alpha 2, a novel antibiotic produced by Streptomyces viridodiastaticus subsp. "litoralis" LL-31F508.
The bioxalomycins, a novel complex of broad-spectrum antibiotics, were isolated from fermentations of Streptomyces viridodiastaticus subsp. "litoralis" LL-31F508. Bioxalomycin alpha 2, the major component of this complex, exhibited antibacterial activity. The MICs ranged from < or = 0.002 to 0.008 micrograms/ml for gram-positive organisms and from 0.50 to 4 micrograms/ml for gram-negative organisms. Bioxalomycin alpha 2 was found to be bactericidal and to inhibit bacterial DNA synthesis preferentially. Bioxalomycin alpha 2 protected mice from a lethal challenge with Staphylococcus aureus Smith. The 50% effective dose of bioxalomycin alpha 2 administered orally was 10 times greater than that when the drug was given subcutaneously or intravenously. These data suggest a stability or bioavailability problem when the compound is administered orally.
Singh
M P
MP
Natural Products Research Section, American Cyanamid Company, Pearl River, New York 10965.
Petersen
P J
PJ
Jacobus
N V
NV
Maiese
W M
WM
Greenstein
M
M
Steinberg
D A
DA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000096:biosynthesis; D005260:Female; D006873:Hydroquinones / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000096:biosynthesis; D013203:Staphylococcal Infections / Q000188:drug therapy; D013302:Streptomyces / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D006873:Hydroquinones; D010080:Oxazoles; D012329:RNA, Bacterial; C090719:bioxalomycin alpha(2)