Effects of the antibiotic resistomycin on the synthesis of macromolecules

Abstract

Resistomycin preferentially inhibits RNA synthesis in comparison to DNA and protein synthesis in intact bacterial cells. Studies with cell-free systems have shown that the antibiotic interferes with DNA and RNA synthesis, while protein synthesis is inhibited to a much lesser extent. Detailed studies in cell-free systems indicate an interaction of resistomycin with DNA-and RNA polymerase. In the case of RNA polymerase this was proved by CD measurements, whereas no interaction of the antibiotic with DNA, RNA, and homopolynucleotides could be found. One can conclude that the binding of the antibiotic to RNA polymerase is the basis for its interference with RNA synthesis.As described earlier (BRADLER and ECKARDT 1972), two antibiotics were isolated from fermentations of Xtreptomyces griseoflavus JA 3733. One of them was shown to be identical with resistomycin which was first isolated by BROCKMANN and SCHMIDT-KASTNER (1954). Resistomycin is an antibacterial and antiprotozoal antibiotic with only very low solubility in water. The chemical structure of resistomycin is shown in This paper describes the action of the drug on intact bacterial cells and its effects on cell-free DNA, RNA, and protein syntheses to localize more precisely the point of attack. Furthermore, the binding ability of the antibiotic to DNA, RNA, protein, and homopolynucleotides was studied by means of spectrophotometric and circular dichroism (CD) measurements and the results have been compared with those obtained by in vivo and in vitro experiments. Materials and methodsFor preparation of resistomycin solutions 1.9 mg of the antibiotic were dissolved in 0.2 ml of 0.1 N NaOH and diluted with water. The antibiotic solution was prepared immediately before use.Synthesis of cellular macromolecules: Bacillus subtilis 168 thy-ind-was grown in glucose-salt medium as previously described (HAUPT and ECKARDT 1972).

Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils

“…Borrelidin and resistomycin are commercially highly relevant natural products. Borrelidin is a nitrilecontaining macrolide that acts as a potent inhibitor of both bacterial and eukaryotic threonyl-tRNA synthetases (Habibi et al, 2012;Nass & Hasenbank, 1970), whilst resistomycin is a pentacyclic polyketide metabolite that inhibits RNA polymerase (Haupt et al, 1975), HIV-1 protease (Roggo et al, 1994) and apoptosis (Shiono et al, 2002), and was first applied as drug for the treatment of tuberculosis. 1-Carbomethoxyphenazine is known to have weaker antimicrobial activity.…”

Heliomycin: Evaluation of its In Vivo Pharmacokinetics in Rats

“…Heliomycin has been isolated from various sources including the marine Streptomyces strain B8005 (Kocket al 2005) and Streptomyces olivocinereus that was isolated from the gut of earthworms (Vinogradova et al 1974). Heliomycin, also called resistomycin or geliomycin, has been shown to have various biological activities: It is cytotoxic against gastric adenocarcinoma HMO2 cells and hepatic carcinoma HePG2 cells with an LC50value lower than 0.02 µg/ml (Adinarayana et al 2006), it was found to have HIV-1 protease inhibiting activity in a concentration of 50 µg/ml (21 µM) (Roggo et al 1994) and has the ability to interfere with both DNA and RNA synthesis through interaction with DNA and RNA polymerases (Haupt et al 1975; Vinogradova et al 1991). It has also been shown to exhibit antibacterial activity against Gram-positive and Gram-negative bacteria with minimal inhibitory concentration of at least 64 µg/ml.…”