Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance
Abstract
The ardA gene, found in many prokaryotes including important pathogenic species, allows associated mobile genetic elements to evade the ubiquitous Type I DNA restriction systems and thereby assist the spread of resistance genes in bacterial populations. As such, ardA contributes to a major healthcare problem. We have solved the structure of the ArdA protein from the conjugative transposon Tn916 and find that it has a novel extremely elongated curved cylindrical structure with defined helical grooves. The high density of aspartate and glutamate residues on the surface follow a helical pattern and the whole protein mimics a 42-base pair stretch of B-form DNA making ArdA by far the largest DNA mimic known. Each monomer of this dimeric structure comprises three alphabeta domains, each with a different fold. These domains have the same fold as previously determined proteins possessing entirely different functions. This DNA mimicry explains how ArdA can bind and inhibit the Type I restriction enzymes and we demonstrate that 6 different ardA from pathogenic bacteria can function in Escherichia coli hosting a range of different Type I restriction systems.
Citation
McMahon , S A , Roberts , G A , Johnson , K A , Cooper , L P , Liu , H , White , J H , Carter , L G , Sanghvi , B , Oke , M , Walkinshaw , M D , Blakely , G W , Naismith , J H & Dryden , D T F 2009 , ' Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance ' , Nucleic Acids Research , vol. 37 , no. 15 , pp. 4887-4897 . https://doi.org/10.1093/nar/gkp478
Publication
Nucleic Acids Research
Status
Peer reviewed
ISSN
0305-1048Type
Journal article
Rights
© 2009 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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