Nicole Moreau

2″-O-Phosphorylation of Gentamicin Components by a Staphylococcus aureus Strain Carrying a Plasmid

A wild-type strain of Staphylococcus aureus that inactivates the 4,6-glycosidically linked deoxystreptamine aminoglycoside antibiotics by a plasmid-mediated process was found to harbor two enzymes: an acetyltransferase of the AAC(6′) type and a new phosphotranferase specific to the gentamicin components. The target of this last enzyme is the 2″-hydroxyl function of these antibiotics, since one inactivated compound is 2″-(O)-phosphorylsisomicin.

Effect of DNA gyrase inhibitors pefloxacin, five other quinolones, novobiocin, and clorobiocin on Escherichia coli topoisomerase I.

Two coumarins, inhibitors of the B subunit of DNA gyrase, and six quinolones, inhibitors of the A subunit, were tested against Escherichia coli topoisomerase I-catalyzed DNA relaxation. Coumarins had no effect, whereas quinolones were inhibitors of the enzyme. This inhibition was compared with that of DNA gyrase and calf thymus topoisomerase I. The 50% inhibitory concentrations for E. coli topoisomerase I were about one order of magnitude higher than the corresponding values for E. coli DNA gyrase but were far lower than the known values for calf thymus topoisomerase I. There was a good relationship between inhibition of the two prokaryotic topoisomerases and MICs for E. coli, and the quinolones could be ranked in the same order in the three cases. Images

Aminoglycoside-modifying enzymes in clinical isolates ofAcinetobacter calcoaceticus

Aminoglycoside-modifying enzymes were identified in clinical strains ofAcinetobacter calcoaceticus subsp.anitratus (Herellea vaginicola) isolated between 1971 and 1979. Resistance to kanamycin, neomycin, and lividomycin was explained by an aminoglycoside-3′-phosphotransferase enzyme. The resistance of gentamicin was due to an aminoglycoside 3N-acetyltransferase type I enzyme which had not previously been described in this species. Several strains producing both enzymes showed resistance to kanamycin, gentamicin, lividomycin, neomycin, and sisomicin and susceptibility to tobramycin and amikacin.

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

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 was found to inhibit protein synthesis in vivo. In vitro, fortimicin A inhibited polyuridylic acid-directed phenylalanine polymerization and induced misreading, as shown by leucine incorporation. In contrast, fortimicin B had no effect on either 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. Both 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.