Effects of elfamycins on elongation factor Tu from Escherichia coli and Staphylococcus aureus.

Antimicrobial Agents and Chemotherapy
C C HallN H Georgopapadakou

Abstract

Six kirromycin analogs (elfamycins) were compared on the basis of their inhibition of Escherichia coli poly(U)-directed poly(Phe) synthesis and stimulation of elongation factor Tu (EF-Tu)-associated GTPase activity. The elfamycins tested were kirromycin, aurodox, efrotomycin, phenelfamycin A, unphenelfamycin, and L-681,217. The last three lack the pyridone ring present in the other elfamycins. All the elfamycins inhibited poly(U)-dependent poly(Phe) synthesis and stimulated EF-Tu-associated GTPase activity, suggesting that the pyridone ring is not essential for activity. The six elfamycins were also examined in a poly(U)-directed, poly(Phe)-synthesizing system derived from Staphylococcus aureus and had 50% inhibitory concentrations of greater than or equal to 1 mM. When S. aureus ribosomes and E. coli elongation factors were combined in a hybrid poly(Phe)-synthesizing system, aurodox produced essentially complete inhibition of poly(Phe) synthesis with a 50% inhibitory concentration of 0.13 microM. This suggests that the observed high MICs of kirromycin and its congeners in S. aureus reflect a kirromycin-resistant EF-Tu rather than permeability constraints.

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Citations

Feb 3, 2011·The Journal of Antibiotics·Elke BrötzHans-Peter Fiedler
Sep 15, 2015·Journal of the American Statistical Association·Juhee LeePeter Müller
Aug 4, 2015·Journal of the American Statistical Association·Ying-Qi ZhaoMichael R Kosorok
Feb 28, 2017·The American Journal of Evaluation·Kelley M Kidwell, Luke W Hyde
Jun 10, 2010·Natural Product Reports·Henning Jacob Jessen, Karl Gademann
Sep 25, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hiroshi Ogawara
Aug 9, 2017·Microbial Genomics·Robert J Goldstone, David G E Smith

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