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Transposase-DNA complex structures reveal mechanisms for conjugative transposition of antibiotic resistance

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Item Type:Article
Title:Transposase-DNA complex structures reveal mechanisms for conjugative transposition of antibiotic resistance
Creators Name:Rubio-Cosials, A. and Schulz, E.C. and Lambertsen, L. and Smyshlyaev, G. and Rojas-Cordova, C. and Forslund, K. and Karaca, E. and Bebel, A. and Bork, P. and Barabas, O.
Abstract:Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes.
Keywords:DNA Complex, Crystallography, Tn1549 Transposon, Tn916-Like Transposon Family, Conjugative Transposition, Tyrosine Recombinase, Antibiotic Resistance, Gene Transfer, Vancomycin, Multidrug-Resistant Bacteria
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:173
Number:1
Page Range:208-220
Date:22 March 2018
Official Publication:https://doi.org/10.1016/j.cell.2018.02.032
PubMed:View item in PubMed

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