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Impact of target site distribution for Type I restriction enzymes on the evolution of methicillin-resistant Staphylococcus aureus (MRSA) populations.

TitleImpact of target site distribution for Type I restriction enzymes on the evolution of methicillin-resistant Staphylococcus aureus (MRSA) populations.
Publication TypeJournal Article
Year of Publication2013
AuthorsRoberts GA, Houston PJ, White JH, Chen K, Stephanou AS, Cooper LP, Dryden DTF, Lindsay JA
JournalNucleic Acids Res
Volume41
Issue15
Pagination7472-84
Date Published2013 Aug
ISSN1362-4962
KeywordsBacterial Proteins, Base Sequence, Computational Biology, Deoxyribonucleases, Type I Site-Specific, DNA Cleavage, DNA Restriction-Modification Enzymes, DNA, Bacterial, Evolution, Molecular, Gene Library, Gene Transfer, Horizontal, Genome, Bacterial, Methicillin-Resistant Staphylococcus aureus, Open Reading Frames, Plasmids
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.

DOI10.1093/nar/gkt535
Alternate JournalNucleic Acids Res.
PubMed ID23771140
PubMed Central IDPMC3753647
Grant List090869MA / / Wellcome Trust / United Kingdom
GR080463MA / / Wellcome Trust / United Kingdom
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