Streptomyces sp. No. B-5050 was found to produce a new antibiotic maridomycin. The taxonomic study on strain No. B-5050 was carried out and this strain was found to be a strain of Streptomyces hygroscopicus (JENSEN, 1931) WAKSMAN et HENRICI, 1948. The cultural condition for the production of maridomycin was also investigated.
A new group of macrolide antibiotics was obtained from the fermentation broth of Streptomyces hygroscopicus No. B-5050. Isolation of six components, maridomycins I, II, III, IV, V and VI, has been accomplished by silica gel adsorption or partition chromatography. They show only end absorption in UV-spectra and are classified as new macrolide antibiotics from their physicochemical, chemical and biological properties.
Maridomycin has been found to have a strong in vitro antibacterial activity against Gram-positive bacteria and some Gram-negative bacteria such as Neisseria gonorrhoeae and Vibrio cholerae. The antibiotic was more active at pH9 than pH6. The antibacterial activity was enhanced by decrease in bacterial inoculum size, but not influenced by the presence of horse serum. The in vitro bacterial resistance to maridomycin was enhanced stepwise by serial transfer, and cross resistance was observed between maridomycin and each of macrolide antibiotics tested. This antibiotic, however, was effective against clinically isolated macrolide-resistant group B and C staphylococci. Furthermore, maridomycin demonstrated bacteriostatic activity and its protein binding ratio examined by cellophane bag dialysis method was found to be low. Maridomycin was as effective as leucomycin on Gram-positive bacterial infection in mice by subcutaneous, intraperitoneal or intravenous administration.
Mass spectrometry has been employed in the study of the antimycin A complex. This has been necessary for two reasons. On one hand, a complete fragmentation scheme is proposed based upon electron ionization, chemical ionization, and accurate mass determinations of the ions in the mass spectra of the antimycin A complex and four simple chemical derivatives. On the other hand, a more rapid qualitative and semiquantitative analysis is shown. Incidental to these findings is the interesting fact that the amide and lactone bonds undergo gas phase ammonolysis.
Using two different molecular orbital methods which treat all valence electrons, namely extended HÜCKEL theory and CNDO/2, a correlation has been found between the biological activity of cephalosporin derivatives and certain aspects of the electronic structure of the β-lactam ring. Electron populations of the carbonyl carbon and bond strength indices of both the carbonyl carbon-nitrogen bond and the carbonyl carbon-oxygen bond in a number of cephalosporin derivatives are correlated with the inhibition of seven strains of gram-negative bacteria by the cephalosporin derivatives. The agreement is more consistent using CNDO/2, which accounts better for long-range inductive effects. It has been found that side chains on the six-membered ring having a positive inductive effect corresponding to the withdrawal of electrons enhance biological activity.
Penicillin acylase was extracted from Escherichia coli strain ATCC 9637, purified and entrapped in celluose triacetate fibres. The enzyme was immobilized by trapping it, as a finely dispersed aqueous phase, in yarns of cellulose triacetate by wet spinning. The kinetics of penicillin G hydrolysis were studied by use of several insoluble preparations with different activity content. In an attempt to evaluate the possible industrial application of the process, the performance of an entrapped acylase reactor was investigated.
The in vitro activity of the aminoglycosides tobramycin and gentamicin was determined through a study using 100 clinical Pseudomonas aeruginosa and 3 international standard strains. Tobramycin was clearly more active against these clinical strains. Comparing the present results with those obtained 3 years ago using gentamicin against 50 strains of the same baterial group, we noticed an evident loss in activity. We report the finding of a gentamicin-resistant tobramycin-sensitive P. aeruginosa strain; this resistance might be due to a chromosomic change rather than to an R-factor.
Mouse skin assays for collagen, determined as hydroxyproline, were carried out on a bleomycin-treated group and on untreated controls. Animals receiving bleomycin showed cutaneous collagen levels approximately 1.75 time higher than those exhibited by the untreated controls. With respect to the ratios of hydroxy proline in soluble collagen fraction to cutaneous total hydroxy proline content, the bleomycin-treated group displayed a roughly 50 per cent decrease in neutral salt soluble fraction and a slight diminution of the acid soluble fraction, as compared with the untreated controls. The findings indicate a significant increase in insoluble collagen content in the skin of mice receiving bleomycin. In an attempt to clarify the mechanism of collagenolysis by the anticancer antibiotic, cutaneous tissue specimens taken from animals treated with the antibiotic were grown in vitro, and crude collagenase preparations isolated from tissue cultures assayed radiologically, using 14C-glycine labelled collagen as the substrate. Lower cutaneous collagenolytic activity was observed in mice treated with bleomycin.