Mode of antibiotic action of 4-hydroxy-3-nitrosobenzaldehyde from Streptomyces viridans

The free ligand, deferroviridomycin A, and its iron(II) complex, viridomycin A, were detected in culture supernatant fluids of Streptomyces viridans 1671 and were structurally characterized as 4-hydroxy-3-nitrosobenzaldehyde and tris(4-hydroxy-3-nitrosobenzaldehydato-N3,O4)ferrate(II), respectively. We investigated the antibiotic activity of the above compounds and of the chemically synthesized bis copper(II), tris cobalt(III), and tris nickel(II) complexes against Escherichia coli NIHJ, Salmonella typhimurium LT-2Z, Staphylococcus aureus 209P, Streptococcus faecium 10541, and Bacillus cereus, T. The free ligand and its kinetically labile copper(II) and nickel(II) complexes displayed activity against all of the above organisms, whereas the kinetically inert iron(II) and cobalt(III) complexes displayed activity only against S. aureus and B. cereus. The antibiotic activity of the substitutionally labile metal complexes was attributed to dissociation of the free ligand. The mode of antibiotic action of the free ligand against E. coli appears to be interference with the structural and functional integrity of the cell membrane.