Roles of two large serine recombinases in mobilizing the methicillin‐resistance cassette SCC mec

• Published in: Molecular microbiology 2013-06, Vol.88 (6), p.1218-1229
• Main Authors: Misiura, Agnieszka, Pigli, Ying Z., Boyle‐Vavra, Susan, Daum, Robert S., Boocock, Martin R., Rice, Phoebe A.
• Format: Article
• Language: English
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.12253

Methicillin‐resistant S taphylococcus aureus ( MRSA ) emerged via acquisition of a mobile element, staphylococcal cassette chromosome mec ( SCC mec ). Integration and excision of SCC mec is mediated by an unusual site‐specific recombination system. Most variants of SCC mec encode two recombinases, CcrA and CcrB , that belong to the large serine family. Since CcrA and CcrB are always found together, we sought to address their specific roles. We show here that CcrA and CcrB can carry out both excisive and integrative recombination in E scherichia coli in the absence of any host‐specific or SCC mec ‐encoded cofactors. CcrA and CcrB are promiscuous in their substrate choice: they act on many non‐canonical pairs of recombination sites in addition to the canonical ones, which may explain tandem insertions into the SCC mec attachment site. Moreover, CcrB is always required, but CcrA is only required if one of the four half‐sites is present. Recombinational activity correlates with DNA binding: CcrA recognizes only that half‐site, which overlaps a conserved coding frame on the host chromosome. Therefore, we propose that CcrA serves as a specificity factor that emerged through modular evolution to enable recognition of a bacterial recombination site that is not an inverted repeat.