In the course of screening for new antibiotics using Piricularia oryzae as a test organism, a new antifungal antibiotic was obtained in crystalline form from the culture broth of a Streptomyces No. 79 strain1) which was isolated from the soil collected in Ikuta, Kawasaki City.
This antibiotic was designated as ikutamycin and its chemical, physical and biological properties were studied. In this paper the authors will describe the isolation and properties.
A new antibiotic, ikutamycin has been isolated from fermentation broth of Streptomyces No. 79 strain of our collection which contains organisms isolated from the soil of Ikuta, Kawasaki City.
In the previous paper1, the isolation and properties of ikutamycin were reported. In this paper, the authors wish to report the taxonomic studies of Streptomyces No. 79 strain.
The structure including the stereochemistry of formycin has been determined by X-ray analysis of its hydrobromide1) This structure, 7-amino-3-[β-D-ribofuranosyl]pyrazolo [4,3-d]pyrimidine, suggests that formycin would be phosphorylated in cells, inhibit the synthesis of purine nucleotides, and be incorporated into RNA. According to Henderson et al.2), this antibiotic affects many points of purine metabolism in chemotherapeutically sensitive Ehrlich ascites tumor cells and 5-phosphoribosylpyrophosphate (PRPP) synthesis is most sensitive to formycin. PRPP systhesis is inhibited at the level of 5-phosphoribose pyrophosphokinase. Ikehara et al.3 have shown that in a system of RNA polymerase and a synthetic DNA as a primer, formycin triphosphate substitutes ATP and in a ribosome system of E. coli, the base of formycin in m-RNA is read as adenine.
While formycin is phosphorylated in Ehrlich carcinoma cells, formycin is deaminated by adenosine deaminase obtained from Aspergillus oryzae as reported in a previous paper4) Recently Niida et al.5) have isolated coformycin from culture filtrates of formycin-producing strains Coformycin is a strong inhibitor of deamination of adenosine and formycin. It is a useful tool to study the effect of formycin in cells, as it inhibits the conversion of formycin to formycin B.
In this paper behavior of formycin in Ehrlich carcinoma cells and E. coli is presented.
As reported in previous papers1,2 formycin is deaminated by adenosine deaminase and converted to formycin B. Adenosine deaminase is widely distributed among living organisms. Therefore, this activity is thought to be exhibited by all kinds of living organisms. Recently Niida et al.3 discovered coformycin which inhibited strongly the enzymatic deamination of formycin and adenosine4). Coformycin is produced by formycinproducing strains and it is thought that coformycin is useful for the production of formycin, inhibiting the conversion of formycin to formycin B.
In this paper, results of testing the deamination activity of washed cells of actinomycetes and bacteria are presented.
Although the preparation of tetracycline by catalytic dehalogenation of chlortetracycline was reported (Boothe et al. 1953), there definite advantages in the direct production of that substance by a fermentation process. Tetracycline is produced instead of chlortetracycline when hibitor of chlorine utilization is added to the medium or when the chlorine ions are removed from the medium (Gourevitch, Misiek & Lein 1955; Minieri, Sokol & Firman 1956). However, some strains, e.g. Streptomyces sp. NCIB 9692 (Palečková, Hošťálek & Řeháček 1966), permit direct production of tetracycline in high concentration in broth containing a substantial content of chloride. The purpose of this paper is to report some of the chief morphologic and physiologic characters of the mentioned strain and to present some comparisons with Streptomyces aureofaciens.
In a search for antibiotic substances among the actinomycetes showing antifungal activity, a group of Streptomyces sp., producing a conjugated triene antibiotic, was isolated from soil samples received from various parts of Brazil.
The production of polyene antibiotics by streptomyces is of widespread occurrence. However, with the exception of a recently described antifungal triene1), all polyenes so far described contain from four to seven conjugated double bonds. The triene producing cultures could be grouped into seven morphologically distinct strains, which, according to the classification scheme of Pridham et al.2), belong to the gray series of the following three morphological sections: Rectus flexibilis (strains E 88; E 872 and E 957); Retinaculum apertum (strains E 784 and E 953); and Spira (strains E 862 and E 887). Apart from microscopical differences, the cultures could be distinguished also by their cultural as well as biochemical characteristics. Nevertheless, the trienes produced by the various isolates showed to be the same compound when examined by paper chromatography, UV, IR and NMR spectroscopy. A detailed taxonomic study of these isolates will be reported in detail separately (Thiemann et al.). In the present paper we wish to report on the production, isolation and characterization of this triene antibiotic named by us mycotrienin.
For these studies only strain E 88 was used. Subsequently the antibiotic activity of some of the other strains were isolated by identical procedures and compared with mycotrienin produced by strain E 88.
Extracellular chromoprotein possessing antibiotic pigment as a prosthetic group was first isolated from the culture of Serratia marcescens by Hattori et al. in 19611), and proved to be prodigiosin-carbohydrate-protein complex. In 1966, Ogawara et al.2 described an antitumor and antimicrobial antibiotic, plurallin, which consists of a prosthetic group resembling to pluramycin and a glycoprotein.
In our screening program for new biologically active substances of microbial origin, a strain of streptomyces, No. CD-270, was isolated from the soil collected in Fukko hot spring district in Taiwan. Deep purple culture filtrate of the strain exhibited antimicrobial and strong anti-HeLa cell culture activities. The filtrate, however, did not display any antitumor activity against Ehrlich and S-180 ascites tumor systems. It was also found that the filtrate did not affect the receptors of such drugs as histamine, acetylcholine, serotonin and nicotine on guinea pig intestine, and produced hypotension in anesthetized rabbit by intravenous injection. According to our previous observation on pharmacological activities of known antibiotics and streptomyces culture filtrates3), cytotoxic antibiotics are classified into two distinct groups by their behavior to the drug receptors on smooth muscle, i.e., those which strongly affect the receptors and those which do not. Most known potential antitumor antibiotics active in vivo are found in the latter group. If the reverse is the case, the response of drug receptors might be employed as a parameter of in vivo activity of various cytotoxic secondary metabolites. It seemed possible, therefore, the anti-HeLa principle in the culture filtrate of strain CD-270 might be active in vivo againit other types of tumors than above two ascites tumor systems. A pigmented macromolecule with antimicrobial, anti-HeLa cell culture and hypotensive effect was thus isolated and designated prunacetin A. The antibiotic was found active on solid types of Ehrlich and S-180 tumors. This paper deals with taxonomy of the strain, production, isolation, physicochemical and biological characteristics of the antibiotic.
Among a number of antibiotics isolated from fungi, griseofulvin and variotin are known effective as chemotherapeutics for certain fungal diseases. In our laboratory, the culture filtrate of a strain of a Fugi imperfecti was found to be effective against several fungi and yeasts in vitro. The strain was named Cephalosporium caerulens as a new species, and a new antifungal antibiotic produced by the organism was given a name of cerulenin.
Cerulenin obtained as white needle crystals is stable in neutral or acid solution, and showed moderately antibacterial activities against several bacteria. The antibiotic inhibited the growth of Candida albicans and Cryptococcus neoformans among fungi in vitro remarkably, and was indicated the curative effect on the infection of Candida albicans in the experimental animals.
The details of cerulenin producing strain 1), the biological assay and the fermentation2), and the biological characteristics of this antibiotic3) have been reported previously. This paper deals with the isolation process and the physico-chemical properties of cerulenin.
The chemistry of aminosugars has been extensively developed in recent years. Many new aminosugars have been found as constituents of useful antibiotics2), nucleotides of bacteria3) and lipo- and muco-polysaccharides4) which occur in microbial cell walls and other cell tissues. The findings of these aminosugars, as well as the discovery of muramic acid in bacterial cell walls and the relation of muramic acid to the mechanism of antibacterial action of penicillin and other antibiotics have deepened the interest in this field of biologically significant compounds. These aminosugars usually occur as a component of polysaccharides or low molecular weight metabolic products, but rarely in a free monosaccharide in nature. Very recently, S. Inouye et al.5) reported the isolation of o-glucopiperidinose (nojirimycin, an antibiotic) produced by Streptomyces sp., and this is the first member of heterose found in nature. In the work reported here, an aminosugar produced by a Bacillus sp. was shown to be the free form of 3-amino-3-deoxy-n-glucose.
Synthetic derivatives6) of 3-amino-3-deoxy-n-glucose have long been known, however, the occurrence of this aminosugar in nature was not revealed until it was found7) as a constituent of the antibiotic kanamycin8) elaborated by Streptomyces kanamyceticus. Since then, new synthesis9,10) of the aminosugar and an improvement11) of the method of Peat and Wiggins8) have been reported.
The bacterium which provides the aminosugar was found during screening for antibiotics exhibiting antibacterial activity against Staphylococcus aureus 209 P The new strain was named Bacillus aminoglucosidicus. This paper is concerned with taxonomy, fermentation, isolation and chemical identification of 3-amino-3-deoxyo-glucose.
It is indispensable for the drug administered orally to be absorbed from the digestive tract and to diffuse into blood and organs. As reported in the previous paper, leucomycin (LM) is absorbed from the intestinal tract when it is given orally, but the blood level is relatively low and assayable blood level is not maintained for a long time. The present experiments have been undertaken to obtain improved preparations with higher and longer blood levels.
In quantitative examination of LM absorption following its oral administration, a remarkable inactivation was noticed when LM was absorbed from intestinal tract. Therefore, the experiments aimed at discovery of substances which prevent such inactivation of LM, combination of such substances with LM, and evaluation of combined administration to mice. The results are presented in this paper.
The field of antibiotics has developed markedly owing to their various biological activities. Up to the present, however, the examination of their pharmacological activities has been carried out only with the agents clinically used. The action of polymyxin B to release endogenous histamine is the most well-known case. The histamine-releasing action of some other basic antibiotics such as streptomycin and kanamycin has been elucidated, though their specific activity is not as strong as polymyxin B1). The study of showdomycin has been carried out in our laboratory and some ovservation was made which suggests that this agent might have acute toxicity similar in some respect to that of histamine releasers2). Therefore, in relation to its strong acute systemic toxicity, we made a comparison of the local reaction caused by showdomycin to that caused by histamine releasers. In the present paper, we examined the effect of showdomycin on the vascular permeability in some rodents and compared it to the effect of other antibiotics including polymyxin B, kanamycin and streptomycin. Analysis of the mechanism of the increase in vascular permeability caused by showdomycin will be made in the following paper.
With the advent of amphotericin B, encouraging progress has been made in chemotherapy of cryptococcal meningitis. Prior to that discovery, no agent had been able to prevent the universally fatal outcome of this disease. Survival rate ranged from 60% to 83 % in recently reported series1,2,3,4) ; this rate refers to the introduction of amphotericin B. This report describes the results of an unusual treatment in a patient with cryptococcal meningitis. The patient was successfully treated with a small amount of amphotericin B, a large amount of prednisolone, and continued removal of cerebrospinalfluid (CSF). Moreover, the latest procedure was considered to be most effective to relieve the symptoms of severe headache and lethargy.