Steffimycin B, an anthracycline, has been isolated from cultures of Streptomyces elgreteus by solvent extraction and purified by silica gel chromatography. NMR and mass spectroscopy indicate the presence of a methoxyl group in the sugar moiety of steffimycin B not found in steffimycin, a related antibiotic. Steffimycin B is not active against bacteria in experimentally infected animals, but has shown some potential antitumor activity in an in vitro screen. Further testing is in progress.
Salinomycin is a new polyether antibiotic produced by a strain of Streptomyces albus (ATCC 21838). The antibiotic is purified by solvent extraction followed by chromatography on alumina or silica gel. It is a weakly acidic compound and has the molecular formula C42H70O11. Salinomycin exhibits activity against gram-positive bacteria including mycobacteria and some filamentous fungi. and is effective in the treatment of coccidial infection of poultry.
One of the vitamin B12 antimetabolites produced by Bacillus cereus 439 has been identified as N5-hydroxy-L-arginine on the basis of its mass-spectrum, 13C-NMR, and mobilities in thin-layer chromatography and paper chromatography in comparison with standard material. The inhibition of growth of Escherichia coli (Davis 113-3)by this compound was reversed by vitamin B12 and was potentiated by L-lysine and 4-hydroxy-L-lysine. Vitamin B12 also partially reversed the inhibition of growth by N5-hydroxy-L-arginine of Pseudomonas aeruginosa, other strains of E. coli, and Klebsiella pneumoniae. While neither N5-hydroxy-L-arginine nor L-lysine affected the growth in tissue culture of KB cells, the mixture of these two amino acids was quite inhibitory.
Fatty acid compositions of strains of Escherichia coli were compared before and after transference of tetracycline resistance factors. Tetracycline-resistant strains contained significantly less C 16:1 and C 17-cyclopropane but more C 16:0 fatty acids than sensitive strains. Doxycycline (10μg/ml) enhanced this trend in resistant strains. 3-Decynoyl-N-acetylcysteamine (DNAC) reversed the effect of doxycycline on resistant strains to a slight degree with respect to C 16:1 and C 17 cyclopropane fatty acids, but produced a significant increase in C 16:0 and decrease in C 18:1 fatty acids. DNAC however did not increase sensitivity to doxycycline in sensitive or resistant strains of E. coli and in certain cases antagonism was observed.
4'-Deoxykanamycin A (12) has been prepared by two different routes (Routes A and B) starting from 6'-N-benzyloxycarbonyl-kanamycin A (1) which was prepared by the selective benzyloxycarbonylation of kanamycin A. The key compounds for the 4'-deoxygenation, N, O-poly-blocked derivatives having a free hydroxy group on C-4', were prepared either by the cleavage of the 4', 6'-cyclic carbamate (7) to the 6'-N-carbethoxy derivative (8) in Route A or by the O→N migration of an acetyl group from the 4'-hydroxy group to the 6'-amino group (13→44) in Route B, 4'-Deoxykanamycin A is significantly more active than kanamycin against Pseudomonas strains and also inhibits the resistant organisms which produce neomycin-kanamycin phosphotransferase II.
The antibiotic action of poly ketoacidomycin (PKAM) on Bacillus subtilis was examined. PKAM stimulated the turnover of phosphatidyl glycerol (PG) to cardiolipin (DPG) and reduced the amounts of the normal fatty acids (nFAs) C-14 and C-16 and anteiso (a) C-17. Addition of bacterial PG to cultures treated with PKAM reduced the effect of the antibiotic. The foregoing changes in lipid composition were associate d with changes in cell permeability . Loss of cellular valine, norvaline and phosphates was observed and a significant decrease in the cellular concentration of Na+ and K+ ions was noted when the test organism was incubate d with PKAM for periods up to 15 minutes. Longer incubation of the bacteria with the antibiotic caused an appreciable increase in RN A content of the cells and a reduction in the DNA and protein content. Polyketoacidomycin (PKAM), first isolated b y SHIMI et al., 1) possesses substantial anti-microbial activity against gram-positive bacteria as well as some gram-negative bacteria. The acid hydrolysate of the antibiotic contains glucose, alanine, and acetone, as well as pyruvic, glyoxylic, α-ketoglutaric, α-ketobutyric and acetoacetic acids.
The effect of antibiotic ASK-753 on cell morphology DNA, RNA and protein syntheses in E. coli, B. subtilis and B. mycoides was studied. In the presence of the antibiotic, gram-positive bacteria formed long filaments, while gram-negative bacteria formed short filaments. It was found that this antibiotic causes inhibition of DNA, RNA and protein syntheses. This inhibition was reversible in E. coli, while it is irreversible in B. subtilis and B. mycoides. By programming the addition and removal of the antibiotic, DNA and RNA syntheses can be made to proceed instepwise increments corresponding to doublings of the DNA. ASK-753 causes the release of 260 mμ absorbing materials from the ASK-753 sensitive strains of B. subtilis. It also lyses protoplasts of B. subtilis but not spheroplasts of E. coli. On the basis of this study, it was concluded that this antibiotic acts primarily on the cellular membrane and consequently leakage of intracellular material occurs.