Comparison of fortimicins with other aminoglycosides and effects on bacterial ribosome and protein synthesis

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Abstract
Fortimicins are bicyclic aminoglycoside antibiotics that contain a fortamine moiety instead of the deoxystreptamine found in other aminoglysides. Fortimicin A had a bactericidal effect on Escherichia coli and Staphylococcus epidermidis and inhibited protein synthesis in vivo. In vitro, fortimicin A inhibited polyuridylic acid-directed phenylalanine polymerization and induced misreading, as shown by leucine incorporation. Fortimicin B had no effect on polymerization or misreading. In assays programmed with natural mRNA, only a weak polymerization inhibition effect was observed with fortimicin A, whereas a strong stimulation was seen in the presence of fortimicin B. Fortimicins A and B inhibited dissociation of 70S ribosomes into their subunits and neither was able to displace [3H]dihydrostreptomycin, [3H]tobramycin or [3H]gentamicin from their respective binding sites on the 70S particle.