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

GWIPS-viz	Trips-Viz

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		Ribo-Seq
	SRR1583083	PRJNA261698	Escherichia coli		Ribo-Seq
	SRR1583084	PRJNA261698	Escherichia coli		Ribo-Seq
	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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