Effect of Mg 2+ and Ethylenediaminetetraacetate on the In Vitro Activity of Coumermycin A 1 and Novobiocin Against Gram-Negative Bacteria

Abstract

The effect of Mg 2+ and ethylenediaminetetraacetic acid (EDTA) on the in vitro activity of coumermycin A 1 and novobiocin was determined against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae , and Proteus mirabilis grown in Trypticase Soy Broth or defined synthetic medium. In the presence of EDTA, the activity of coumermycin A 1 was significantly enhanced (8- to 40-fold) against all four organisms in the synthetic medium lacking Mg 2+ ; novobiocin activity was increased to a lesser extent (4- to 16-fold) against three strains and remained unchanged against P. mirabilis. Addition of 200 μg of Mg 2+ per ml to the synthetic medium containing EDTA completely reversed the enhancement of activity of both antibiotics by EDTA only against P. aeruginosa. The addition of Mg 2+ to the synthetic medium appreciably inhibited the activity of novobiocin (sixfold) but not coumermycin A 1 against E. coli , and had little or no effect on the activity of either antibiotic against the remaining organisms. K. pneumoniae showed the greatest susceptibility to both antibiotics, and addition of EDTA enhanced this activity from 4-fold to 20-fold in all of the media tested. Subinhibitory concentrations of both antibiotics induced filament formation by all four organisms in all media. In addition, lysis of K. pneumoniae cells was observed.