Studies in the previous papers1),2),3),4) call for an observation on the phenomenon of resistance to dihydrostreptomycin. The present investigations were carried out in order to examine the metabolic reactions of a strain of E. coli which has became risistant to dihydrostreptomycin.
At present, considerable informations were presented on the inhibitory actions of chloramphenicol on enzymatic reactions in both growing and resting bacterial cells. The following reactions are reported as to the inhibitions of chloramphenicol; the formation of adaptive enzyme1,2) or the synthesis of protein,3–5) the activity of bacterial lipase,6) the reduction of nitrite,7) the metabolism of aromatic amino acids8–10) and the oxidation of dicarboxylic acids.11–12)
Recently the production of α-ketoglutarate with many kinds of microorganisms has been reported and also a number of studies17),20),35–39) put forward on the mechanism of α-ketoglutarate fermentation.
Some pathways of the production of α-ketoglutarate from glucose were already suggested as follows; (I) α-ketoglutarate was produced from glucose via pyruvate and (II) α-ketoglutarate was formed directly from glucose (C6 → C5+ CO2), so that its formation did never occur through pyruvate nor by condensation of pyruvate with the fragment such as C2- or C3-compound produced during fermentation. The first pathway (I) may again be divided into following two ways; (a) the one via the tricarboxylic acid cycle and (b) the other via a pathway different from the tricarboxylic acid cycle. Katagiri and Tochikura40) supported the pathway (I)-(b) with coli-aerogenes bacteria and suggested a new pathway in which α-ketoglutarate is formed by the condensation reaction of pyruvate and acetyl-Co A.
As regards the action of chloramphenicol upon the reaction system of the formation of α-ketoglutarate from pyruvate, there suggested at least three ways; the first was the inhibiting action on the formation or breakdown of citrate (in case of (I)-(a)), the second was its action on the condensation reaction of pyruvate and acetate, (in case of (I)-(b)) and the third was the case in which E. coli fermented pyruvate specifically in the presence of chloramphenicol by other pathways different from both conventional tricarboxylic acid cycle and pyruvate-acetate reaction.
In the present papers, investigations have been undertaken to trace the mode of action of chloramphenicol with the purpose of examining of the possibilities of these three ways mentioned above.
In the previous paper1) of this series, the procedure of isolation of antibiotics ayamycins A and B from the cultured liquid of Streptomyces No. O-80 and their biological properties were presented. At that time, the crude powder was found to exhibit an antitumor effect and anti-bacterial effect. While further fractionation showed that ayamycin A complex was responsible for the major part of the anti-tumor activity in the cultured liquid.
During the course of screening anti-tumor antibiotics in our laboratory, it has been found that many exhibit an anti-tumor effect in the so-called actinomycin-type antibiotics.2) Ayamycin was also included in actinomycin-type antibiotics.3) However, it was of interest to note that this compound differed considerably from the known actinomycin-type antibiotics, in that the in vitro anti-tumor effect was stronger than the antibacterial effect, and that it contained a quinone structure.
In subjecting the ayamycin A complex to a modified Vining’s paper chromatography procedure4) for isolation of actinomycin components, it was found that several components existed, and among these, A2 was obtained as a yellow needle crystal. This A2 crystal was responsible for the major part of the anti-tumor activity in A complex.
In this paper, further details on isolation and purification of ayamycin A complex and physico-chemical characteristics of the crystal obtained from A2 fraction are presented.
An orange rod crystalline antibiotic pigment having acid-base-indicating property has been isolated from the culture of a strain of Streptomyces. This organism, indexed I-523 in our culture collection, has been isolated from a soil sample collected from Minō Park, Osaka Prefecture. The antibiotic, which we have named minomycin, possesses highly significant activity against the gram-positive organism and shows some inhibitory effect on Ehrlich ascites tumor and Crocker sarcoma in vitro.
In the present paper, we intend to describe the antibiotic-producing organism and to, report the production, isolation, chemical properties, antimicrobial spectrum, and anti-tumor activities of minomycin.
The present interest in staphylococcal infections has been induced by increased incidence of staphylococci resistant to increasing number of antibiotics and their indiscriminate use. It is now an important hospital problem,1),2),3),4) and septicemia due to antibiotic-resistant staphylococci have remained a serious therapeutic problem at the persent time. The mortality-rate of staphylococcal septicemia occurring in adults has still remained approximately from 50 to 70%.6),10),29) It must be generally accepted that the therapeutic results were much different with the cases even if the antibiotics, to which the strain isolated from the patients was sensitive, were used in proper combination. The discrepancies between the sensitivity test in vitro and clinical effects were shown in several literatures.24)
During the past 6 years there were 15 instances of staphylococcal septicemia including hospital-acquired cases at the First National Hospital in Tokyo. The present paper is concerned with a clinical analysis of this series with therapeutic considerations and the emergence of antibiotic-resistant strains of staphylococci isolated from the patients and healthy carriers in this country.