Elimination of resistance determinants from R-factor R1 by intercalative compounds

Abstract

Eighteen deoxyribonucleic acid (DNA)-complexing compounds, among them 15 intercalative substances, and, additionally, nalidixic acid eliminated with different frequencies four antibiotic resistance determinants from the R-factor R1, carried by Salmonella typhimurium. Eliminating concentrations did not inhibit growth of the bacteria. The most active compound was "nitroacridine II" {1-diethylamino-3-[(6-nitro-9-acridinyl)amino]propanol}. When 14 compounds which had been tested at a standard concentration of 10(-4) M were listed according to decreasing activities of elimination of the four resistance determinants, a nearly consistent activity sequence was revealed. Frequencies of elimination of the kanamycin resistance determinant correlated directly with the binding of compounds to DNA, i.e., with end points of their displacement of methyl green from the methyl green-DNA complex. We propose that the observed eliminations resulted from selective toxicity for plasmidic template DNA and inhibitions of R-factor replication.