Kannan et al. 2014 (PRJNA261698)

General Details

Title The general mode of translation inhibition by macrolide antibiotics
Organism
Number of Samples 3
Release Date 2014/09/22 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP047380
ENA SRP047380
GEO GSE61619
BioProject PRJNA261698

Publication

Title
Authors Kannan K, Kanabar P, Schryer D, Florin T, Oh E, Bahroos N, Tenson T, Weissman JS, Mankin AS
Journal Proceedings of the National Academy of Sciences of the United States of America
Publication Date 2014 Nov 11
Abstract Macrolides are clinically important antibiotics thought to inhibit bacterial growth by impeding the passage of newly synthesized polypeptides through the nascent peptide exit tunnel of the bacterial ribosome. Recent data challenged this view by showing that macrolide antibiotics can differentially affect synthesis of individual proteins. To understand the general mechanism of macrolide action, we used genome-wide ribosome profiling and analyzed the redistribution of ribosomes translating highly expressed genes in bacterial cells treated with high concentrations of macrolide antibiotics. The metagene analysis indicated that inhibition of early rounds of translation, which would be characteristic of the conventional view of macrolide action, occurs only at a limited number of genes. Translation of most genes proceeds past the 5'-proximal codons and can be arrested at more distal codons when the ribosome encounters specific short sequence motifs. The problematic sequence motifs are confined to the nascent peptide residues in the peptidyl transferase center but not to the peptide segment that contacts the antibiotic molecule in the exit tunnel. Therefore, it appears that the general mode of macrolide action involves selective inhibition of peptide bond formation between specific combinations of donor and acceptor substrates. Additional factors operating in the living cell but not functioning during in vitro protein synthesis may modulate site-specific action of macrolide antibiotics.
PMC PMC4234590
PMID 25349425
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR1583082 PRJNA261698 Escherichia coli 0.0 Ribo-Seq 0.0
SRR1583083 PRJNA261698 Escherichia coli 0.0 Ribo-Seq 0.0
SRR1583084 PRJNA261698 Escherichia coli 0.0 Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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