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© Pierre Gounon
Entrée de Listeria dans une cellule épithéliale (Grossissement X 10000). Image colorisée.
Publication : Proceedings of the National Academy of Sciences of the United States of America

HflXr, a homolog of a ribosome-splitting factor, mediates antibiotic resistance

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 13 Dec 2018

Duval M, Dar D, Carvalho F, Rocha EPC, Sorek R, Cossart P

Link to Pubmed [PMID] – 30545912

Proc. Natl. Acad. Sci. U.S.A. 2018 12;115(52):13359-13364

To overcome the action of antibiotics, bacteria have evolved a variety of different strategies, such as drug modification, target mutation, and efflux pumps. Recently, we performed a genome-wide analysis of gene expression after growth in the presence of antibiotics, identifying genes that are up-regulated upon antibiotic treatment. One of them, , is a homolog of , which encodes a heat shock protein that rescues stalled ribosomes by separating their two subunits. To our knowledge, ribosome splitting has never been described as an antibiotic resistance mechanism. We thus investigated the role of in antibiotic resistance. First, we demonstrated that is an antibiotic resistance gene that confers protection against lincomycin and erythromycin, and that we renamed ( resistance). We show that expression is regulated by a transcription attenuation mechanism relying on the presence of alternative RNA structures and a small ORF encoding a 14 amino acid peptide containing the RLR motif, characteristic of macrolide resistance genes. We also provide evidence that HflXr is involved in ribosome recycling in presence of antibiotics. Interestingly, possesses another copy of , , that is not involved in antibiotic resistance. Phylogenetic analysis shows several events of duplication in prokaryotes and widespread presence of in Firmicutes. Overall, this study reveals the as the founding member of a family of antibiotic resistance genes. The resistance conferred by this gene is probably of importance in the environment and within microbial communities.

https://www.ncbi.nlm.nih.gov/pubmed/30545912