Pyrrolnitrin preferentially inhibited the oxidation of NADH-linked substrates in monkey kidney cells, and in rat liver mitochondria (RLMw) and the oxidation of NADH by submitochondrial particles (SMP) of beef heart. The antibiotic inhibited the reduction of 2, 6-dichlorophenolindophenol and cytochrome c by NADH and by succinate, but it did not affect the flavins of NADH dehydrogenase and succinate dehydrogenase. Pyrrolnitrin probably blocked electron transfer between the dehydrogenases and the cytochrome components of the respiratory chain. The effect on the phosphorylation of ADP (RLMw) and energy transduction (SMP) as indicated by the fluorescence of 8-anilino-naphthalene-1-sulfonic acid were secondary. Reduced pyrrolnitrin had similar effects on respiration, but it was a less potent inhibitor.
Spiramycin-uptake by Staphylococcus aureus MS537 was not affected by the presence or absence of glucose and Mg in media and was not inhibited by uncoupling agents of oxidative-phosphorylation. Maximal spiramycin-uptake by MS537 took place at pH 7 and within 20 minutes of addition of the drug. Spiramycin-uptake and growth inhibition curves with MS537 increased in parallel from pH 5 to 7. Despite a decrease in spiramycin-uptake from pH7 to 9, growth inhibition remained constant. Spiramycin-uptake by MS537 after induction of spiramycin-resistance was half the uptake before induction. Spiramycin-uptake by constitutively resistant mutant of MS537 was the same level as that of induced population of MS537. The affinity of ribosomes for spiramycin, derived from MS537 after induction or from a constitutively resistant mutant of MS537, was one fifth to one tenth that of ribosomes prepared from MS537 before induction.
This paper deals with kinetic studies on the induction of resistance to tetracycline (TC) in Staphylococcus aureus. It was found that TC-resistance is inducible and TC is an active inducer. Cell populations acquired high resistance to TC after prior exposure to subinhibitory concentrations of the drug, but the resistance of induced populations was lost when the cells were grown in the absence of inducer. Induction of TC-resistance did not take place when protein synthesis of bacteria was inhibited by addition of chloramphenicol or actinomycin D, and by histidine starvation in a histidine auxotroph. The acquisition of resistance to tetracycline was paralleled by a decrease in the accumulation of the drug in bacterial cells, resulting from a decrease in their permeability for tetracycline.
Antimycin A is a complex of four major components designated as A1, A2, A3 and A4, which were isolated, A4 for the first time, in pure crystalline form. All components exhibited the same fungicidal activity, using Saccharomyces cerevisiae Y-30 as the test organism ; the higher activity of A3 reported before was found to be only apparent, and could be attributed to its higher diffusion coefficient in agar. The teleocidal activity was also the same for all components. Mutations to increased production of antimycin A do not necessarily lead to a change of composition; but, in the various mutants examined, when a change in composition was observed, it was in favor of A1. Three new minor components, designated as A0, A5 and A6, have been detected which represent not more than 1 % of the complex.
A relatively rapid method for the qualitative and semiquantitative analysis of the components present in the antimycin A complex is described. The method is based on the pyrolysis of the antimycin A complex and subsequent gas liquid chromatography of the pyrolysate. The mass spectra of isolated GLC fractions from the pyrolysate of pure antimycin A components are also used to support the chemical structure of the antimycin molecule.
The antimycin A- blastmycin antibiotics are strong fungicides which have been separated into the components antimycin A1, A2, A3 (blastmycin) and A4. The structures of A1 and A3 were elucidated as I. Gas-liquid chromatographic studies of the antibiotic derivatives revealed additional components. Degradation products from the antibiotics were also investigated by gas-liquid chromatography to determine individual antibiotic structures. The blastmycin complex and antimycin A complex can be classified respectively into four and about nine members, which differ in alkyl side chain and acyloxy groups as listed in Fig. 3.