The antibacterial activity and enzymatic inactivation of lividomycin, a new aminoglycosidic antibiotic, were studied with 13 strains of Pseudomonas aeruginosa. The minimal inhibitory concentration of lividomycin was 12.5 to 25 mug/ml, and three strains were resistant to high concentrations of lividomycin (more than 200 mug/ml). It was found that P. aeruginosa TI-13 and K-11, highly lividomycin-resistant strains of clinical origin, strongly inactivated the drug. The third resistant strain, Km-41/R, was developed in vitro. Unlike the other resistant strains, Km-41/R, was developed in vitro. Unlike the other resistant strains, Km-41/R did not inactivate the drug, indicating that different mechanisms were involved in lividomycin resistance. By use of a cell-free extract from P. aeruginosa TI-13, the inactivation of lividomycin was found to be caused by the formation of a monophosphorylated product of the drug.

Drug Resistance, Microbial↗

PubMed1972

Antibacterial activity of lividomycin toward R factor-resistant strains of Escherichia coli.

Forty-eight R factors conferring resistance to both kanamycin (KM) and streptomycin (SM) were demonstrated from 1,270 Escherichia coli strains of clinical origin. Among these R factors isolated, 42 also conferred resistance to the new antibiotic lividomycin (LV). Extracts of E. coli ML1410 carrying one such factor (R(M81)) inactivated LV as well as KM and SM. But extracts of E. coli ML1410 carrying an R factor (R(M82) or R(M83)) sensitive to LV could not inactivate LV. LV inactivation required both adenosinetriphosphate (ATP) and Mg(2+). Inactivated LV was reactivable by alkaline phosphatase. Isotopic studies with labeled ATP and elemental analysis of the reaction product indicate that it is a monophosphorylated derivative of LV.

Drug Resistance, Microbial↗

PubMed1972

Phosphorylation of lividomycin by Escherichia coli carrying an R factor.

A lividomycin-phosphorylating enzyme from a lividomycin-resistant strain of Escherichia coli carrying an R factor was partially purified by fractionation with ammonium sulfate and Sephadex G-100 column chromatography. The enzyme inactivated, in the presence of adenosine triphosphate and Mg(2+), several antibiotics having a d-ribose moiety linked to 2-deoxystreptamine, i.e., lividomycin A and B, neomycin, paromomycin, and vistamycin, but did not inactivate the kanamycins, streptomycin, or the gentamicin C components. Chemical studies of the inactivated product suggested that the phosphorylated site of the inactivated lividomycin was the hydroxyl group of the d-ribose moiety.

Drug Resistance, Microbial↗

PubMed1972