Pyrrolnitrin inhibits the syntheses of protein, RNA and DNA to almost the same degree. It also inhibits respiration but this site does not seem to be the primary action. It does not inhibit the biosynthesis of porphyrin. It is not an uncoupler of oxidative phosphorylation. It inhibits the transport of many substances, and causes the leakage of A260mμ absorbing materials inside the cells. Pyrrolnitrin bursts the protoplasts of Bacillus megaterium KM strain at the growth inhibitory concentration. This action is completely neutralized by an approximately equimolar concentration of some phospholipids in the cell membrane components. It is concluded that the primary damage by pyrrolnitrin occurs in the cell membrane through a combination of pyrrolnitrin and some phospholipids.
A mixture of ampicillin (aminobenzyl penicillin, AB-PC) and cloxacillin (methylchlorophenylisoxazolyl penicillin, MCI-PC) showed an excellent bactericidal activity even at low concentrations in which either of the penicillins alone did not have any activity against a clinically isolated strain of Escherichia coli, resistant to both of these penicillins. In this case, the microbial degradation of AB-PC, caused by penicillinase (PC-ase), was strongly inhibited in the presence of MCI-PC. The enzymatic hydrolysis of AB-PC by extracellular and cell-bound PC-ase, obtained from an AB-PC resistant strain of Staphylococcus aureus, was also inhibited in the presence of MCI-PC. Against that, under comparable conditions, penicillin G (PC-G) was almost completely destroyed by cell-bound PC-ase from this organism. An in vivo synergism was observed when mixtures of AB-PC and MCI-PC were applied for the treatment of mice challenged with a clinically isolated strain of E. coli resistant to both of these penicillins. Similar results were obtained in the treatment of mice experimentally infected with a strain of Staphylococcus aureus, which is highly resistant to AB-PC, but sensitive to MCI-PC.
The mechanism of the action of xanthocillin X monomethylether (XME) on multiplication of Newcastle disease virus (NDV) in cultured cells was studied. The inhibitory effect of XME was exerted whenever the antibiotic (15μg/ml) was added during the viral one-step growth cycle, and the effect could be reversed after removal of the antibiotic by washing. A lag period of approximately 5 hours was observed before the restoration of hemagglutinin synthesis had occurred. Pretreatment of host cells with XME for 7 hours and subsequent removal of the antibiotic did not affect velocity and yield of virus production. XME completely inhibited protein synthesis in both virus infected and mock-infected cells, however total actinomycin D-insensitive RNA synthesis was found to be practically the same in antibiotic-treated cells as in the control. Actinomycin D-insensitive RNA synthesized in the presence of XME was more heterogeneous than the control using methylated albumin-kieselguhr (MAK) column chromatography. Antiviral activity of XME was compared with that of other antibiotics known to be inhibitors of protein synthesis. XME was found to be one of the best inhibitors among all compounds tested, due to its low cytotoxicity and low effective concentration in agar-diffusion plaque-inhibition tests.
Dianemycin is an antibiotic previously reported to affect cation transport and to be effective in treating coccidiosis in chickens. It is isolated from a fermentation broth of Streptomyces hygroscopicus. The compound was found to be primarily active against gram-positive organisms. The chemical properties of dianemycin indicate a close relationship to monensin and other acidic cation complexing compounds.
Mycophenolic acid (MA) inhibits the growth of some pathogenic fungi such as Candida albicans, Cryptococcus neoformans and several species of Trichophyton at low concentrations in vitro. The antibiotic is more effectvie against fungi at slightly acidic pH than neutral pH. When administered to mice through the intraperitoneal, intramuscular and oral routes MA excreted to a few per cent in the urine. However, at no time was active MA detectable in the blood of mice. MA is effective against experimental trichophytosis of the guinea pigs, without noticeable skin irritation or inflammation.