Detection of Staphylococcal Cassette Chromosome mec Type XI Carrying Highly Divergent mecA , mecI , mecR1 , blaZ , and ccr Genes in Human Clinical Isolates of Clonal Complex 130 Methicillin-Resistant Staphylococcus aureus

Abstract
Methicillin resistance in staphylococci is mediated by penicillin binding protein 2a (PBP 2a), encoded by mecA on mobile staphylococcal cassette chromosome mec (SCC mec ) elements. In this study, two clonal complex 130 (CC130) methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients in Irish hospitals were identified that were phenotypically PBP 2a positive but lacked mecA by conventional PCR and by DNA microarray screening. The isolates were identified as methicillin-susceptible S. aureus using the GeneXpert real-time PCR assay. Whole-genome sequencing of one isolate (M10/0061) revealed a 30-kb SCC mec element encoding a class E mec complex with highly divergent blaZ-mecA-mecR1-mecI , a type 8 cassette chromosome recombinase ( ccr ) complex consisting of ccrA1-ccrB3 , an arsenic resistance operon, and flanking direct repeats (DRs). The SCC mec element was almost identical to that of SCC mec type XI (SCC mec XI) identified by the Sanger Institute in sequence type 425 bovine MRSA strain LGA251 listed on the website of the International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements. The open reading frames (ORFs) identified within SCC mec XI of M10/0061 exhibited 21 to 93% amino acid identity to ORFs in GenBank. A third DR was identified ca. 3 kb downstream of SCC mec XI, indicating the presence of a possible SCC remnant. SCC mec XI was also identified in the second CC130 MRSA isolate by PCR and sequencing. The CC130 MRSA isolates may be of animal origin as previously reported CC130 S. aureus strains were predominantly from bovine sources. The highly divergent nature of SCC mec XI relative to other SCC mec elements indicates that it may have originated in another taxon.

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