Gerald H. Wagman

Binding of Aminoglycoside Antibiotics to Filtration Materials

An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials.

Antibiotic G-418, a New Micromonospora-Produced Aminoglycoside with Activity Against Protozoa and Helminths: Fermentation, Isolation, and Preliminary Characterization

Antibiotic G-418 is a new aminoglycoside produced as the major component by a new species of Micromonospora, M. rhodorangea NRRL 5326. The antibiotic is prepared by submerged fermentation in a soybean-dextrin medium. Antibiotic G-418 is adsorbed on a cationic-exchange resin and separated from other impurities by passing it down a Dowex (1 × 2) resin column. The antibiotic, which contains 2-deoxystreptamine, has broad-spectrum antibacterial activity and is highly active against protozoa, amoebae, tapeworm, and pinworm infections in mice. This report describes the taxonomy of the organism, and fermentation, isolation, and preliminary characterization of antibiotic G-418. Images

Verdamicin, a New Broad Spectrum Aminoglycoside Antibiotic

Verdamicin is a new aminoglycoside antibiotic isolated from fermentation broths of a species of the genus Micromonospora, M. grisea. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be similar to those of gentamicin and sisomicin.

Binding of Aminoglycosides to Feces

Gentamicin and several other basic antibiotics were examined for their ability to adsorb to dog feces. It was found that 44 to 90% of all antibiotics studied were adsorbed to feces depending on the ratio of antibiotic to fecal material. Attempts to extract these antibiotics by acid treatment after adsorption onto feces were only partially successful since large portions of the bound materials were not removed.

A New Actinomycin Complex Produced by a Micromonospora Species: Fermentation, Isolation, and Characterization

A species of Micromonospora, Micromonospora floridensis NRRL 8020, has been found to produce an actinomycin complex consisting of at least 25 active components. After solvent extraction of the complex, separation of the individual components was carried out by preparative thin-layer chromatography. Hydrolysis and subsequent electrophoretic and chromatographic identification of the amino acid content of each of the isolated components have shown differences from known actinomycins, and the probability exists that these contain a number of amino or imino acids not previously found in other members of this group of antibiotics.

Micromonospora-Produced Gentamicin Components

After the chromatographic separation of [methyl-14C]gentamicin major (C) components from a large-scale radioactive fermentation (Lee et al., 1974), [methyl-14C]gentamicin minor (polar) components (A, B, B1, X2, and G-418) were isolated from subsequent chromatography of the remaining antibiotic mixture. When l-[methyl-14C]methionine was added at the onset of biosynthesis of the gentamicin components, incorporation of label into the minor components preceded incorporation into the major components. Degradation occurred when [methyl-14C]gentamicin major components (C1, C2 and C1a) were added respectively to the gentamicin-producing culture medium and shaken. Images

Biotransformation of Sisomicin to Gentamicin C2b

Sisomicin was transformed to gentamicin C2b by Micromonospora rhodorangea NRRL 5326. The mechanisms involved in the biotransformation are the 6′-N-methylation and the (4′-5′)-reduction. The progression of the methylation was followed by the isotope technique, but the reduction reaction was not monitored.

New Polyene Antifungal Antibiotic Produced by a Species of Actinoplanes

A new species of Actinoplanes, which has been deposited with the designation NRRL 5325 at the Northern Utilization Research and Development Division of the U. S. Department of Agriculture, produces a polyene antifungal complex designated as Sch 16656. The complex, consisting of one major and three minor components, is isolated from the fermentation broth by a solvent extraction procedure and purified by precipitation methods. The major component is a heptaene and is highly active in vitro and in vivo against Candida albicans. It is active also against strains of Torulopsis and is significantly more potent orally than candicidin in mice against Candida infections. Images

Biological Activity of Sch 14342, an Aminoglycoside Antibiotic Coproduced in the Gentamicin Fermentation

Sch 14342 is an aminoglycoside antibiotic coproduced as a minor component in the gentamicin fermentation. Sch 14342 was found to have the same antibacterial spectrum as gentamicin in vitro and in vivo, and was approximately one-third as active in mouse protection tests. Sch 14342 relative to gentamicin was one-third as toxic in acute tests in mice, one-eighth as toxic in renal toxicity tests in dogs, and an estimated one-tenth as toxic in cat ataxia tests. Sch 14342 possesses a significantly improved therapeutic index relative to gentamicin with reference to ataxia potential and renal toxicity.

Discovery and isolation of sisomicin

SummarySisomicin was isolated from fermentation broths of a new species of the genus Micromonospora, specifically M. inyoensis, and was differentiated from other related antibiotics by a variety of chemical and biological methods. Chromatographic and analytical data indicated that it differed from gentamicin C1a only by the presence of a double bond in one of the amino sugar constituents. Sisomicin was found to be up to five times as active as gentamicin in vitro and in mouse protection studies against selected organisms.ZusammenfassungSisomicin wurde aus der Fermentationsbrühe eines neuen Stamms der Gattung Micromonospora, nämlich M. inyoensis, isoliert und durch eine Vielzahl chemischer und biologischer Methoden von anderen verwandten Antibiotika differenziert. Chromatographische und analytische Daten zeigten, daß es sich nur durch eine Doppelbindung einer der Aminozuckerkomponenten von Gentamicin C1a unterscheidet. Sisomicin war gegen ausgewählte Stämme in vitro und bei Tierversuchen mit infizierten Mäusen (‘mouse protection study’) bis zu fünfmal wirksamer als Gentamicin.