A new antitumor antibiotic, sporamycin, was isolated from the culture broth of Streptosporangium pseudovulgare strain No. PO-357.* Sporamycin was prepared as a white powder by ammonium sulfate precipitation and chromatographic techniques using DEAE-cellulose and Sephadex G-50. The producing organism was similar to Streptosporangium pseudovulgare in a number of properties but differed in the biological activity of the culture broth and the color of the aerial mycelium on agar. Sporamycin is active against most Gram-positive bacteria and Sarcoma-180 solid tumors. It is heat labile, but stable at low temperature.
Some strains belonging to the genera Bacillus and Pseudomonas were found to produce in the culture broth, a protein which synergistically enhanced the activity of macrolide antibiotics against Pseudomonas aeruginosa. The protein produced by Bacillus brevis ATCC 8185, designated SP127, was isolated in a pure state by means of ammonium sulfate fractionation, CM-cellulose column chromatography and gel filtration on Sephadex G-100. The sedimentation coefficient and the molecular weight of SP127 were 1.8 s and 15, 000, respectively according to the analytical ultracentrifuge. The isoelectric point of SP127, obtained by electrofocusing experiments, was over 10.0. Half cystine and histidine were absent in the molecule.
Antibiotics, the activity of which was enhanced against Pseudomonas aeruginosa by SP127, were restricted to the basic macrolide antibiotics such as erythromycin, maridomycin and oleandomycin, the neutral macrolide antibiotics such as lankamycin and lankacidin C, vancomycin and enramycin. Synergistic activity of SP127 with the above antibiotics was found against Pseudomonas aeruginosa and several strains of Escherichia coli, but not against Proteus vulgaris and macrolide-resistant Staphylococcus aureus. SP127 had extremely weak proteolytic but no lytic activity. From the isotopic experiments, the action of SP127 was partially attributed to the promotion of antibiotic penetration to cells of Pseudomonas aeruginosa.
Three crystalline antibiotics which we named striatins A, B, and C were isolated from the mycelium of the basidiomycete Cyathus striatus strain No. 12. The striatins are highly active against fungi imperfecti and a variety of Gram-positive bacteria, as well as against some Gram-negative bacteria. The molecular formulas as determined by mass spectrometry are C27H36O7 for striatin A, C27H36O8 for striatin B, and C25H34O7 for striatin C.
Characteristics of a mutant of Cephalosporium acremonium with enhanced potential to utilize sulfate for cephalosporin C production were investigated with sulfur-starved cells. DL-Norleucine showed an inhibitory effect on cephalosporin C and penicillin N production by the mutant in the presence of a sulfur source such as sulfate, sulfite, thiosulfate, and L-cystine, but it exhibited no effect when it was added after a certain period of incubation. On the contrary, antibiotic production by the parent was stimulated by norleucine regardless of the addition time. An increase in the intracellular cysteine pool was found when the cells were incubated with L-methionine or norleucine and sulfate. Enzymatic studies revealed that methionine and norleucine stimulated the cysteine desulfhydrase formation, and this effect was significant in the mutant. Finally the mutant was found to have an enhanced L-serine sulfhydrylase activity. The increase in this enzyme activity in the mutant seems responsible for the increase in the sulfate-utilizing ability and the methionine sensitivity by maintaining a high level of the cysteine pool. Accordingly, the effect of methionine and norleucine is assumed to be exerted through cysteine.
Soil supports the growth of a jute pathogen Colletotrichum gloeosporioidesbut only to a limited extent that of its antagonist Aspergillus versicolor. The growth of the sensitive pathogen is considerably checked by the antagonist in mixed soil culture although versicolin production could not be demonstrated within the limits of assay. Both the sensitive and the antagonistic organisms grow well in soil-compost medium and versicolin production by the latter is also enhanced. The antagonistic effect of Aspergillus versicolor on Colletotrichum gloeosporioides is expectedly more marked in soil-compost medium than in soil medium.
The effects of a monovalent cation ionophore etheromycin (CP-38295) and a divalent cation ionophore lysocellin on blood platelets function have been investigated. When platelets were incubated with 3 μM of each ionophore, the simultaneous induction of secretion of stored serotonin and efflux of intracellular calcium occurred, but there was no detectable influx of extracellular calcium. With increasing concentrations, these compounds caused platelet aggregation accompanied by increased influx of external calcium. These results are consistent with the hypothesis that the liberation of calcium from the intracellular store mediates the platelet secretion reaction.
The effect of aurodox on its own biosynthesis by Streptomyces goldiniensis was studied. It was found that addition of exogenous aurodox inhibits further accumulation of aurodox by the antibiotic-producing culture. Both long term fermentation studies with aurodox-14C and precursor incorporation studies over short time periods indicated that aurodox synthesis was regulated by feedback inhibition. The concentration of aurodox required to completely block further synthesis of the antibiotic was about 400μg/ml. This is the same as the maximum concentration of aurodox normally accumulated by the culture used in this study. Antibiotic synthesis was inhibited not only by aurodox but also by some structural analogs of aurodox including several having no antibacterial activity. This effect was immediate and readily reversible, indicating that it could be due to inhibition of an enzyme(s) involved in the biosynthesis of aurodox.
Resistant colonies develop with an apparent high frequency in zones of inhibition around fosfomycin filter discs on nutrient agar. The resistance is due, primarily, to loss of the fosfomycin transport system. The resistant colony type usually observed in the inhibition zones seldom arise directly by mutation from a cell sown in the area of the zone of inhibition. Instead, small translucent colonies develop first in the inhibition zone. Within these small translucent colonies, mutational events occur which give rise to the normal resistant type colonies.
Mycobacillin, a cyclic polypeptide antifungal antibiotic effectively inhibits the growth of promastigote form of the protozoal organism, Leishmania donovani, strain 81 in liquid medium. Oxygen uptake by intact cells of the protozoa with exogenous glucose is appreciably reduced within first 30 minutes in presence of the antibiotic at a concentration of 15μg/ml. Appreciable leakage of intracellular 260 nm and 280 nm absorbing materials takes place from the protozoan cells incubated with the antibiotic at similar concentration.