title: Impact of target site distribution for Type I restriction enzymes on the evolution of methicillin-resistant Staphylococcus aureus (MRSA) populations.
abstract: A limited number of Methicillin-resistant Staphylococcus aureus (MRSA) clones are responsible for MRSA infections worldwide, and those of different lineages carry unique Type I restriction-modification (RM) variants. We have identified the specific DNA sequence targets for the dominant MRSA lineages CC1, CC5, CC8 and ST239. We experimentally demonstrate that this RM system is sufficient to block horizontal gene transfer between clinically important MRSA, confirming the bioinformatic evidence that each lineage is evolving independently. Target sites are distributed randomly in S. aureus genomes, except in a set of large conjugative plasmids encoding resistance genes that show evidence of spreading between two successful MRSA lineages. This analysis of the identification and distribution of target sites explains evolutionary patterns in a pathogenic bacterium. We show that a lack of specific target sites enables plasmids to evade the Type I RM system thereby contributing to the evolution of increasingly resistant community and hospital MRSA.
authors.affiliation: EaStCHEM School of Chemistry, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JJ, UK and Division of Clinical Sciences, St. George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
authors.forename: Gareth A
authors.initials: GA
authors.lastname: Roberts
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Houston
authors.forename: John H
authors.initials: JH
authors.lastname: White
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Augoustinos S
authors.initials: AS
authors.lastname: Stephanou
authors.forename: Laurie P
authors.initials: LP
authors.lastname: Cooper
authors.forename: David T F
authors.initials: DT
authors.lastname: Dryden
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Lindsay
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods; D053837:DNA Cleavage; D015280:DNA Restriction-Modification Enzymes / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics; D015253:Deoxyribonucleases, Type I Site-Specific / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D015723:Gene Library; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D055624:Methicillin-Resistant Staphylococcus aureus / Q000201:enzymology / Q000235:genetics*; D016366:Open Reading Frames; D010957:Plasmids / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015280:DNA Restriction-Modification Enzymes; D004269:DNA, Bacterial; C113046:HSDS protein, Bacteria; C109829:HsdM protein, Bacteria; D015253:Deoxyribonucleases, Type I Site-Specific