Permanent chlorosis of Euglena gracilis cells induced by streptomycin was described by Provasoli, et al.1) and Jírovec2) some years ago. This effect of streptomycin on green flagellates was supposed to be a specific property of streptomycin. In the dark, these green flagellates also become chlorotic, but this effect is reversible; chlorophyll rapidly regenerates in light. Aminotriazole is also only a temporary inhibitor of chlorophyll synthesis3).
There are many papers on the permanent bleaching effect of streptomycin. Goodwin and Gross4) have examined streptomycin-bleached substrains for their carotenoid content. The content of usual carotenoids in these substrains is at best only one fifth of the content in normal green strains. We studied quantitative differences between the enzymatic equipment of green and by-antibiotics-depigmentated euglenas5). In 1961 we described a similar bleaching effect of erythromycin6).
In the course of our studies concerned with some side-effects of antibiotics we found that kanamycin also causes permanent chlorosis of cells of Euglena gracilis. So far many similar properties of streptomycin and kanamycin are known, e. g. the effect on Mycobacterium tuberculosis, their chemical structure etc. Therefore, kanamycin is counted among streptomycin-like antibiotics. A permanent chlorosis caused by kanamycin is a further property showing the relationship of streptomycin and kanamycin.
In the course of searching for new antibiotics active against tubercle bacilli, a new antibiotic named tuberin was obtained from the culture broth of Streptomyces amakusaensis which will be reported elsewhere. The present paper deals with the isolation and physical and chemical properties as well as biological properties.
A culture filtrate of a streptomyces inhibited growth of S. aureus 209 P on a semisynthetic medium, Knight medium, but exhibited no inhibition against this organism growing on a nutrient agar. This active substance was isolated and crystallized as the calcium salt and the identity with PA 147, 3-carboxy-2, 4-pentadienal lactol reported by Els, Sobin and Celmer1) was confirmed. This antibiotic was found to have inhibitory activity against HeLa cells and ascites and solid forms of Ehrlich carcinoma.
Characters of the streptomyces producing PA-147 has not been described. In this paper, characters of the strain producing this antibiotic and production, isolation, and properties of the antibiotic are presented.
Streptothricin or streptothricin-like substances show delayed toxicity and this kind of toxicity is considered to be due to a kidney damage caused by these substances. If a kidney is damaged and excretion of the toxic substance is delayed, then the toxic substance accumulates and causes stronger kidney damage, and finally the animals are led to death. In such a case, when a minimal lethal dose is injected, the animals are expected to die a few or several days after the injection. A substance which reduces toxicity of streptothricin may reduce toxicity of other water-soluble basic substances, because water-soluble basic substances having free amino group may be detoxicated by the same mechanism. The present studies were made for a purpose of finding a substance reducing ototoxicity of useful antibiotics such as streptomycin and kanamycin.
A substance having amino group may be detoxicated through formation of glucuronide, then it is interesting to examine the effect of those substances which are expected to stimulate the detoxicating system of basic substances. From another view point, a basic substance which has low toxicity to kidney may compete with streptothricin in the binding sites in kidney cells and may expel streptothricin from the cells. From these two kinds of aspects, the authors examined influnces of pyrimidine derivatives for the effect of reducing toxicity of streptothricin, and a preliminary result 1s presented in this paper.
Culture filtrates of actinomycetes were screened for the activity of selectively inhibiting growth of B. subtilis and its mutant requiring adenine, cytosine and uracil. A culture filtrate was found to inhibit growth of B. subtilis more strongly than the mutant in certain synthetic medium. The active substance was isolated and confirmed to be o-carbamyl-d-serine. The isolation of this substance from a streptomyces had been reported by Hagemann, Pennasse and Teillon1), but these authors did not describe characters of the streptomyces. Characters of the streptomyces which was isolated by the present authors and which produced o-carbamyl-d-serine, processes for the isolation and some biological activities of this substance are presented in this paper.