In the course of our screening program of antimycoplasma antibiotics produced by Streptomycetes, some of the fermentation broths showed a wide inhibition zone on the agar plate of mycoplasma. Some of these active components were isolated from the fermentation broths and determined to be bottromycin1,2,3,4,5), actinoleukin6), actinomycin7,8,9) and pluramycin10). The present paper deals with the screening method of antimycoplasma antibiotics using the agar plate culture of mycoplasma and the determination of in vitro activities of antibiotics against Mycoplasma mycoides var. mycoides.
A causal organism of primary atypical pneumonia (PAP) was first isolated by Eaton1) and later it was characterized by Chanock as Mycoplasma pneumoniae2). Other mycoplasmas such as M. orale, M. hominis and M. salivarium are inhabitants of the human oropharynx, and have called attention of microbiologists as the contaminant of various tissue cultures3). Although considerable informations about the effect of antibiotics against the mycoplasmas originated from animals like chicken4) have been accumulated, only a few reports are available on the effects of antibiotics against human mycoplasmas5,6). This is in part due to the difficulty of growing human mycoplasmas in cell free condition and to the lack of convenient assay system for the antibiotic activity. A prior publication from this laboratory described the in vitro assay method as well as the effect of various antibiotics on Mycoplasma pneumoniae Mac6). Obtained results indicated that almost all of the macrolide antibiotics and some antitumor agents inhibited M. pneumoniae at lower dose level than those of tetracyclines as far as tested on agar plates by pulp-disc diffusion assay.
Employing the same assay system, it has been possible to test the effect of many antibiotics against the growth of other mycoplasmas isolated from human oropharynx. Thus, the present study was designed firstly to investigate the in vitro activity of various antibiotics against some human mycoplasmas, and to compare their activities with those against M. pneumoniae. On the way of such efforts, it was noticed that the antibiotics which are able to eliminate such mycoplasmas from tissue cultures should be rather looked for. Thus the present paper will also concern to the effect of selected antibiotics on the growth of mycoplasmas in tissue culture.
A new antiviral antibiotic, bihoromycin, has been isolated from the fermentation broth of a strain of streptomyces named Streptomyces filipinensis var. bihoroensis nov. var. This antibiotic is a colorless needle crystal and markedly inhibited the TMV-local lesion formation on the leaf of pinto bean.
This paper summarizes the characteristics of the new Streptomyces strain and some of the chemical, physical and biological properties of bihoromycin.
In the course of screening antibiotics, a new crystalline antibiotic primarily active against staphylococci was obtained from the culture harvest of Streptomyces bruneogriseus nov. sp. MCRL-0129 and other strains of Streptomyces (MCRL-0355 and MCRL-0356). The antibiotic was named albocycline due to its color and cyclic nature. Physico-chemical and biological properties of albocycline resemble to those of cineromycin B reported by Miyairi et al.1), but definite differences were found between both antibiotics.
The present paper deals with the production, isolation, and physico-chemical and biological properties of albocycline. The taxonomic studies of albocycline-producing strains will be reported later.
The quinoxaline antibiotics constitute a family of antibiotics with a chromopeptide structure1) and differ solely in the peptide portions of the molecule2). There are as many as twelve antibiotics in this group produced biosynthetically from Streptomyces3,4). We have previously reported that quinoxaline antibiotics inhibit growth of gram-positive bacteria5), exhibit a cytotoxic effect upon tissue culture cells and are active against various transplantable tumors6,7). Of special interest is the finding that there was no cross-resistance among the specifically resistant strains of Staphylococcus aureus against different quinoxaline antibiotics8) in spite of the small difference in chemical structure. In contrast, PuGH et al.9) reported that S. aureus, which is resistant to actinomycin D, showed a significant cross-resistance to other actinomycin complexes, which likewise represent another large family of chromopeptide antibiotics10).
The preceding publication11) reported the investigations that quinomycins are potent inhibitors of ribonucleic acid (RNA) synthesis in the protoplasts of Escherichia coli, which is normally insensitive to these antibiotics.
This report presents the results of preliminary studies to determine the mechanism of action of quinomycins against bacteria. These antibiotics principally inhibit the synthesis of RNA by S. aureus, and specifically bind to deoxyribonucleic acid (DNA) in vitro. Recently, Ward et al.12) reported that echinomycin (quinomycin A), like actinomycin, binds with DNA and inhibits DNA-directed enzymic RNA synthesis. The results obtained here are similar to those reported previously with echinomycin12) and actinomycin13).
Detailed informations of metabolic events occurring during the cell division cycle can be obtained by synchronized culture of mammalian cells and some informations about the mode of action of the drug could be obtained by studying the effect of a drug added at varying stage of the cell division cycle. Using synchronized culture of HeLa cells,
Kajiwara et al.1) found that phleomycin blocked the cells to enter prophase without any
appreciable inhibition of DNA, RNA and protein syntheses.
The present paper deals with the comparative study of the effects of phleomycin and two additional antibiotics, bleomycin and formycin, on synchronized HeLa S3 strain cells. Phleomycin, a copper-containing peptide antibiotic, was isolated from St. verticullus by Maeda et al2). Its specific inhibition in vitro of DNA polymerase reported by Falashi et al. 3) and Tanaka4) has attracted our attention. Bleomycin was isolated from St. verticullus5) and found to be closely related with phleomycine6) in chemical properties7) as well as in antitumor activity. Formycin, 7-amino-3-(β-D-ribofuranosyl)-pyrazolo (4,3-d) pyrimidine8), inhibiting Ehrlich carcinoma was isolated from Nocardia interforma9). Its antibacterial, antifungal and antiviral10) activities were reported. Formycin was converted11) in a sensitive strain of >Ehrlich ascites carcinoma to its triphosphate derivative, a proposed active form, and interfered with nucleotide synthesis by depressing 5-phosphoribosyl-1-pyrophosphate synthesis12.
Since the first two antibiotics are closely related to each other and the last one is a different type of antibiotic, the study was initiated by our interest in comparing the modes of action of these three antibiotics in the synchronized cell culture.
Julimycin B-11, a new antibiotic produced by Streptomyces shiodaensis nov. sp. 1), was found to exhibit a chemoprophylactic effect against poliovirus infections in mice2), and its structure was determined by Tsun3) as shown in Fig. 1. In the present study, the antitumor activities of this new antibiotic were examined.
Studies to obtain certain useful cephalosporin derivatives have been carried out in this laboratories for several years. In the course of these studies, certain derivatives were found to be effective for the treatment of experimentally induced infections in mice. Among these, the m-chlorophenylacetyl derivative of 7-aminocephalosporanic acid (7-ACA) was evidenced to have powerful antibacterial activity against gram-positive bacteria both in vitro and in vivo1). It is presumed that the administered antibiotic has been widely distributed in sufficient concentration to be therapeutically effective for enough period. From the standpoint of clinical uses of this agent, it has been desirable to clarify its distribution in the tissues.
The present investigation was undertaken, using 14C-labeled m-chlorophenylacetyl derivative of 7-ACA, in order to estimate the metabolic fate of this agent.