Preferential Inhibition of Protein Synthesis by Ketolide Antibiotics in <Emphasis Type="Italic">Haemophilus influenzae</Emphasis> Cells |
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Authors: | W Scott Champney Craig L Tober |
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Institution: | (1) Department of Biochemistry and Molecular Biology, J.H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA, US |
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Abstract: | The ketolide antibiotics are semi-synthetic derivatives of erythromycin A with enhanced inhibitory activity in a wide variety
of microorganisms. They have significantly lower MICs than the macrolide antibiotics for many Gram-positive organisms. Two
ketolides, telithromycin and ABT-773, were tested for growth-inhibitory effects in Haemophilus influenzae. Both antibiotics increased the growth rate and reduced the viable cell number with IC50 values of 1.5 μg/ml. Protein synthesis was inhibited in cells with a similar IC50 concentration (1.25 μg/ml). Macrolide and ketolide antibiotics have been shown to have a second equivalent target for inhibition
in cells, which is blocking the assembly of the 50S ribosomal subunit. Pulse and chase labeling assays were conducted to examine
the effect of the ketolides on subunit formation in H. influenzae. Surprisingly, both antibiotics inhibited 50S and 30S subunit assembly to the same extent, with no specific effect of the
compounds on 50S assembly. Over a range of antibiotic concentrations, 30S particle synthesis was diminished to the same extent
as 50S formation. H. influenzae cells seem to have only one significant target for these antibiotics, and this may help to explain why these drugs are not
more effective than the macrolides in preventing the growth of this microorganism.
Received: 21 February 2002 / Accepted: 30 April 2002 |
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