To be effective in inhibiting R-factor transfer (between Escherichia coli strains) and infection of E. coli with phage f 2, requinomycin must be present at the time of initiation of both events. Delayed addition of requinomycin showed no or slight inhibition. No direct effect of requinomycin on phage f2 or E. coli strains employed was observed. The intact cell surface of E. coli must be impermeable to requinomycin as shown by the fact that DNA synthesis by toluene-treated E. coli cells (permeability modified) was markedly inhibited by requinomycin, in contrast to its ineffectiveness on intact E. coli cells. Therefore, requinomycin probably acts without penetrating the cells. Probable mechanism of action is discussed.
Studies on lividomycin A, a new broad-spectrum aminoglycosidic antibiotic, , were conducted in rats, rabbits and dogs to determine its plasma levels, urinary and biliary excretion as well as tissue distribution. Intramuscular administration of lividomycin A resulted in high potentially therapeutic plasma concentration with concentration depending on the dose. Seventy to 90% of drug administered intramuscularly to dogs and rabbits was recovered in the urine primarily within 8 hours of dosing. In contrast only 2% of an oral dose was recovered in rabbit urine, indicating poor absorption from the gut. Biliary excretion was measurable but minimal. High concentrations of the antibiotic were observed in the plasma, lung and kidney of the rats, with slow clearance from the kidney. Thin-layer chromatography of dog urine gave no evidence for the presence of biologically active metabolites. All studies indicated that lividomycin A behaved similarly to kanamycin.
A new antibiotic, rosamicin, classified as a macrolide, has been isolated from the fermentation broth of a new species of Micromonospora, M. rosaria. The antibiotic is separated from the broth by a solvent extraction procedure and purified by column chromatography. Chromatographic studies indicate that rosamicin is different from all related macrolides and is a novel antibiotic. It has broad-spectrum activity, although it is more potent against gram-positive organisms. Rosamicin is also active against Mycoplasma.
Rosamicin is a new Micromonospora-produced macrolide antibiotic with activity equal to or superior to erythromycin and megalomicin A against grampositive bacteria and improved activity against gram-negative bacteria. Rosamicin is highly active against a variety of Mycoplasma and anaerobe species. Some erythromycin-resistant, megalomicin A-resistant strains of Staphylococcus aureus are sensitive to rosamicin confirming a lack of complete cross resistance. Rosamicin, megalomicin A and erythromycin have comparable in vivo activity on the basis of mouse protection tests.
A new antibiotic, cryomycin, was isolated from the culture filtrate of a facultatively psychrophilic streptomycete. As a result of taxonomic studies, it was considered a new subspecies for which the name Streptomyces griseus subsp. psychrophilus, YOSHIDA, TANI and OGATA, is proposed. The type strain is AKU 2881. This organism grows at 0-37°C and produces cryomycin at 0-18°C. Cryomycin is a peptide antibiotic containing a rather large amount of glycine in its molecule. It darkens at 214-217°C with decomposition. This antibiotic is highly active against Gram-positive bacteria in vitro. The LD50 in mice by intravenous injection is 150 mg/kg.
The mode of action of tomaymycin (TM) which is a new antibiotic with antitumor activity was studied. Inhibition of the incorporation of labeled precursors into the acid-insoluble fraction of Bacillus subtilis cells indicated that TM inhibits nucleic acids biosynthesis, while having relatively little effect on protein synthesis. TM displaced methyl green (MG) from a MG-DNA complex and a TM-DNA complex was isolated by gel filtration chromatography. The formation of the TM-DNA complex resulted in (1) shifts of UV absorption profiles of TM and the corresponding difference spectra, (2) increase in the melting temperature of DNA, (3) protection of native DNA from degradation by nuclease O. These findings are compatible with the proposition that TM exerts its action as a growth inhibitor by forming a complex with DNA which in turn prevents the DNA from participating as a template in the biosynthesis of nucleic acids.
Sibiromycin, possessing strong antitumor activity in animal experiments, is produced by Streptosporangium sibiricum. Sibiromycin can be isolated from culture filtrate using ion-exchange or by solvent extraction. The antibiotic was obtained as a crystalline substance with ultraviolet absorption maxima at 230 and 310 nm, [α]D+525° (in dimethylformamide); the empirical formula-C24H31N3O7. In 1 N hydrochloric acid, sibiromycin is transformed into "the product of acidic inactivation" (PAI), C24H29N3O6. Hydrolysis of PAI with 6 NHC1 affords "the product of acidic hydrolysis" (PAH), C16H14N2O3. Methanolysis of sibiromycin and PAI yields the methylglycoside of a new amino sugar sibirosamine, C8H16NO3 (OCH3). Aqueous alkaline hydrolysis of PAI and PAH affords the crystalline substance C8H9NO.