Although Geotrichum species occur ubiquitously, antibiotic production by members of this genus has not previously been reported. The antibiotic complex designated A25822, consisting of one major and six minor structurally-related components active primarily against Candida and Trichophyton, represents a new family of naturallyoccurring compounds. Approximately 90% of the antibiotic activity synthesized remained associated with the fungal cell mass, from which it was recovered by multiple methanolic extractions for quantitation. Antibiotic production was enhanced by tryptophan. iron, zinc, and high levels of dextrin.
A novel group of antibiotics, comprising microbiologically-active structurallyrelated factors A25822A, B, D, H, L, M and N, produced by culturing Geotrichum flavo-brunneum NRRL 3862 under submerged aerobic fermentation conditions was isolated by extraction. The individual factors were separated and purified by chromatography and crystallization. The major factor, A25822B, a 15-aza-24-methylene-D-homocholestadiene is a white crystalline compound, C28H45NO. The antibiotics are highly active against fungi and marginally active against bacteria.
The A25822 antibiotic complex consists of seven biologically active factors. A comparative study of these factors determined that factor B possessed the greatest antifungal activity. The minimal inhibitory concentration of A25822B against isolates of Candida albicans was <0.312-5.0μg/ml, Trichophyton mentagrophytes was inhibited at <0.0312μg/ml. Other pathogenic fungi such as Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatitidis, Sporotrichum schencki, and Microsporium gypseum were very susceptible to A25822B. Only limited antibacterial activity of A25822B was found. Parenteral or oral administration of 50mg/kg of A25822B significantly extended the average survival time of mice infected with C. albicans. Doses of 20mg/kg of A25822B caused a greater than ten-fold reduction in the number of Candida cells recovered from kidneys of infected mice. A solution of 0.5% or 0.25% A25822B applied topically was effective against an experimental dermatophyte infection on guinea pigs. A peak blood level of 3 μg/ml was achieved in mice following a 100mg/kg dose of A25822B. Combination of A25822B with a polyene antibiotic in vitro showed antagonism.
A new antibiotic, lysocellin (K-5610), was isolated from Streptomyces cacaoi var. asoensis K-9 Met-. Lysocellin was obtained as a colorless crystalline needles from both the cultural filtrate and the mycelium of the organism. The antibiotic melted at 158-160°C and had a molecular formula C34H59O10Na•1/2 H2O. It had antimicrobial activity against gram-positive bacteria, antibiotic-resistant Staphylococcus aureus and some fungi, but not against gram-negative bacteria. Based on its physico-chemical and biological properties lysocellin was identified as a new polyether antibiotic.
Two water-soluble basic antibiotics named galantins I and II were isolated from a strain resembling Bacillus pulvifaciens. Both antibiotics are peptides containing glycine, alanine, ornithine, lysine and some unknown ninhydrin-positive components. An approximate empirical formula C50±1H98±2O17N16 indicated for galantin I. These are active against some gram-positive, acid-fast and gram-negative bacteria.
A new antibiotic TL-119 active against gram-positive bacteria was isolated from a strain resembling Bacillus subtilis. The antibiotic is a neutral substance, soluble in a mixture of chloroform and methanol, and is a peptide with an empirical formula of C42H57N7O9, containing threonine (1), alanine (1), valine (1), leucine (1) and phenylalanine (2).
A new antibiotic named 61-26 active against gram-positive bacteria and some fungi was isolated from a Bacillus strain. The antibiotic is a weakly basic peptide slightly soluble in aqueous alcohols. An approximate empirical formula of C50H93-N11O17 and constituent amino acids of aspartic acid (1 mole), serine (2 moles), alanine (2 moles), and sum of valine and isoleucine (2 moles) are indicated.
In solid form, amphotericin B and amphotericin B methyl ester free base exhibit similar stability. Acid salts of the methyl ester derivative stored under identical conditions are less stable. In solution, amphotericin B is generally more stable than its methyl ester salts. However, when pH is adjusted to 6.0 and storage temperature held at 5°C the methyl ester salts reflect the stability exhibited by the parent compound, amphotericin B.
Degradation of DNA in HeLa-S3 cells mediated by an acidic antitumor protein, neocarzinostatin (NCS), was examined. The concentration of NCS required for induction of DNA degradation was considerably higher than that which caused inhibition of DNA synthesis. Sedimentation analysis of DNA revealed that HeLa-S3 cell DNA first received single-strand nicks within 60 minutes after exposure to the antibiotic, whereas detectable double-strand scissions eventually gave rise to the accumulation of double-stranded DNA fragments of heterogeneous size. When the cells exposed to NCS were transferred to NCS-free medium at early stages of the degradation, the single-strand nicks caused in DNA were repaired by a process which was sensitive to puromycin.
Sisomicin, a new aminoglycoside antibiotic which is produced by Micromonospora myoensis, was studied against 565 clinical isolates of gram-negative bacilli and gram-positive cocci. With the exception of Serratia marcescens, over 90% of isolates of gram-negative bacilli were inhibited by 1.56μg/ml or less of sisomicin. Sisomicin was slightly more active than gentamicin and tobramycin against isolates of Escherichia coli, Proteus mirabilis and Klebsiella spp. It was substantially more active than butirosin and kanamycin against all gram-negative bacilli. Isolates of gram-negative bacilli which were resistant to gentamicin and tobramycin were also resistant to sisomicin. Most of these isolates were sensitive to amikacin.
Radioactivity incorporated into individual components and subunits of each component was determined, following chromatographic separation and hydrolytic degradation of components of methyl-14C-gentamicin complex.