A new antibiotic named platenocidin was isolated from the culture broth of Streptomyces H 273 N-SY2 and the producing microbe was classified as Streptomyces platensis. Platenocidin gives 5-hydroxymethyluracil by acid or alkaline hydrolysis and can be considered to belong to one of the nucleoside antibiotics. The antibiotic inhibits the growth of certain species of yeasts, but not that of bacteria.

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A series of basic 16-membered macrolide antibiotics, M-4365 A₁, A₂, A₃, G₁, G₂ and G₃, were isolated from the culture broth of strain MCRL 0940 which is assigned to be a new species of Micromonospora and for which the name Micromonospora capillata sp. nov. is proposed. Among these antibiotics, M-4365 A₂ and G₂ showed strong inhibitory activity against Grampositive and Gram-negative bacteria.

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By physicochemical analyses and chemical procedures, the structures of a series of basic 16-membered macrolide antibiotics, M-4365 A₁, A₂, A₃, G₁, G₂, and G₃ were elucidated, and it was found that M-4365 A₁, G₁ and G₂ were novel, while M-4365 A₂, A₃ and G₃ were identical with rosamicin, juvenimicins A₄ and B₁, respectively.

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Antibiotic G7063-2, isolated from a Streptomyces species, is a new nitrogen-containing analogue of phyllostine and terreic acid. In vitro G7063-2 is moderately active against both Gram-positive and Gram-negative bacteria and weakly active against fungi. It is toxic to mice.

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Glycinothricin is a streptothricin-class antibiotic obtained for the first time from the culture broth of a strain of Streptomyces griseus. Glycinothricin, the deformimino derivative of antibiotic LL-AB664, gives N-methylstreptolidine, N-methyl-D-glucosamine and glycine on acid hydrolysis. In comparison with LL-AB664, glycinothricin is less active against gram-positive and gram-negative bacteria and less toxic to mice.

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The structures of melinacidins II, III and IV were determined by physicochemical methods. Melinacidin IV is considered to be identical to 11α, 11α'-dihydroxychaetocin while melinacidins II and III are isomeric to chaetocin and verticillins A and B.

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Addition of clindamycin to whole-cell cultures of Streptomyces coelicolor MÜLLER resulted in the loss of in vitro activity against organisms sensitive to clindamycin. Incubation of such culture filtrates with crude alkaline phosphatase generated a biologically active material identified as clindamycin. Fermentation broths containing inactivated clindamycin yielded clindamycin 3-ribonucleotides and clindamycin 3-phosphate the structure of which was established by physicochemical and enzymatic means. Attempts to transform clindamycin to clindamycin 3-ribonucleotides by lysates or partially purified enzyme preparations from S. coelicolor have failed.

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Using a strain of Streptomyces hygroscopicus JA 6599 several ¹⁴C-compounds were investigated as potential precursors of the macrolide antibiotic turimycin followed by partial degradation to localize the radioactivity. L-Methionine-¹⁴C-methyl and n-butyrate-1-¹⁴C were incorporated exclusively and in a specific manner. The incorporation ratios were dependent on the addition time of the precursors. Studies of the incorporation of acylmycaroses and demycarosyl turimycin into the antibiotic are also reported.

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Based on the experimental results that 3-formyl rifamycin SV acts as an uncoupler in vitro on rat liver mitochondria, the effect of some rifampicin derivatives on the K⁺ and H⁺ compartmentation of biological membranes was examined to obtain a chemiosmotic hypothesis
for oxidative phosphorylation. The K⁺ release from mitochondria was remarkably stimulated by 3-formyl rifamycin SV in accordance with uncoupling of the oxidative phosphorylation. 3-Formyl rifamycin SV also stimulated the K⁺ release from red blood cells, though its action was not as effective as in mitochondria. It can be suggested that 3-formyl rifamycin SV interacts with biological membranes, causing a change in permeability to ions, especially of K⁺ and H⁺ through the mitochondrial membrane, resulting in uncoupling of the oxidative phosphorylation.

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Four DNA-dependent RNA-polymerases were separated from the cell homogenate of mouse Leukemia L1210 cells by DEAE-cellulose column chromatography and tentatively designated as Peaks I, II, III and IV in the elution order. Peak II was inactivated by the addition of α-amanitin and effects of antibiotics and enzymes on the RNA-polymerase activity using Peaks I, II and a mixture of Peaks I and II were examined. The RNA-polymerases were used to screen for enzyme inhibitors produced by microbes. This enzymatic method was successfully proved to select antitumor antibiotics.

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The cytotoxicity and biochemical effects of several marketed antibiotics on four mammalian cell lines were determined. Several metabolites of clindamycin and several clinically useful anticancer drugs were also included in this study. The four cell lines were mouse leukemia L1210, human oral carcinoma KB, human acute myelogenous leukemia RPMI 6410, and human lymphocyte RPMI 1788. At concentrations of 0.4 μmole/ml, ampicillin, lincomycin and penicillin G were not lethal for L1210 cells, nor had they any significant inhibitory effects on the growth of the other cell lines. Tetracycline was the most cytotoxic
antibiotic tested, followed by clindamycin and erythromycin, cephaloglycin, and chloramphenicol. In general, inhibition of cell growth paralleled lethality for L1210 cells. Tetracycline was also found to have a stronger inhibitory effect than clindamycin on DNA, RNA, and protein synthesis in human RPMI 6410 cells. Drug effects on macromolecular synthesis correlated closely to those on cell growth. Among the clindamycin metabolites, clindamycin sulfoxide and clindamycose were nontoxic and only N-demethyl clindamycin had an activity equivalent to that of clindamycin. The structure-activity relationships of these metabolites are briefly discussed. None of the antibiotics tested, with the possible exception of tetracycline, however, approached the potency exhibited by most anticancer drugs. The lack of potential for these antibiotics as anticancer drugs is discussed. The biological and biochemical effects on mammalian systems observed with clindamycin are discussed in terms of the possible relation to pseudomembranous colitis.

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The bactericidal activity of penicillin-aminoglycoside combinations was studied in 16 strains of Group B streptococci. Minimal inhibitory concentrations (MIC) against kanamycin or gentamicin were greater than 50μg/ml, whereas ampicillin or penicillin inhibitory concentrations were uniformly less than 0.1μg/ml. Although all strains had bactericidal concentrations (MBC) less than 0.1μg penicillin/ml, penicillin at a concentration equal to each strains respective MBC reduced inoculum colony forming units (CFU) 2 logs in only 6 of 16 strains in bactericidal kinetic studies. However, the addition of gentamicin in concentrations of 5.0 or 10.0μg/ml to penicillin markedly enhanced bactericidal activity in all strains tested. The addition of lower concentrations of gentamicin (1.0μg/ml) had minimal advantage over penicillin alone. No distinct advantage was noted for combinations including either ampicillin or kanamycin. The theoretical advantage of penicillin-aminoglycoside combinations in experimental conditions, suggests that the use of antibiotic combinations in clinical infections due to Group B streptococci, may result in a more rapid eradication of these organisms.

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