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Transient erythromycin resistance phenotype associated with peptidyl-tRNA drop-off on early UGG and GGG codons
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
2007 (English)In: Journal of Bacteriology, ISSN 0021-9193, Vol. 189, no 24, 8993-9000 p.Article in journal (Other academic) Published
Abstract [en]

Expression of minigenes encoding tetra- or pentapeptides MXLX or MXLXV (E peptides), where X is a nonpolar amino acid, renders cells erythromycin resistant whereas expression of minigenes encoding tripeptide MXL does not. By using a 3A' reporter gene system beginning with an E-peptide-encoding sequence, we asked whether the codons UGG and GGG, which are known to promote peptidyl-tRNA drop-off at early positions in mRNA, would result in a phenotype of erythromycin resistance if located after this sequence. We find that UGG or GGG, at either position +4 or +5, without a following stop codon, is associated with an erythromycin resistance phenotype upon gene induction. Our results suggest that, while a stop codon at +4 gives a tripeptide product (MIL) and erythromycin sensitivity, UGG or GGG codons at the same position give a tetrapeptide product (MILW or MILG) and phenotype of erythromycin resistance. Thus, the drop-off event on GGG or UGG codons occurs after incorporation of the corresponding amino acid into the growing peptide chain. Drop-off gives rise to a peptidyl-tRNA where the peptide moiety functionally mimics a minigene peptide product of the type previously associated with erythromycin resistance. Several genes in Escherichia coli fulfill the requirements of high mRNA expression and an E-peptide sequence followed by UGG or GGG at position +4 or +5 and should potentially be able to give an erythromycin resistance phenotype.

Place, publisher, year, edition, pages
2007. Vol. 189, no 24, 8993-9000 p.
Keyword [en]
Protein synthesis inhibitor, Macrolide, Antibacterial agent, Erythromycin, Mutation, Antibiotic, Codon, tRNA, Phenotype, Resistance
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-14351DOI: 10.1128/JB.01004-07ISI: 000251992800025PubMedID: 17951392OAI: oai:DiVA.org:uu-14351DiVA: diva2:42121
Available from: 2008-01-29 Created: 2008-01-29 Last updated: 2010-02-24Bibliographically approved

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