Structural features of the genome of methicillin-resistant Staphylococcus aureus (MRSA), a ceftaroline-resistant representative of ST239 epidemic clone isolated in Russia

Abstract

Genomic analysis of methicillin-resistant ceftaroline-resistant Staphylococcus aureus and identification of features of the genetic diversity in representatives of the epidemic ST239 clone circulating in hospitals of the Russian Federation. Species identification was performed using Vitek 2 (bioMerieux). Determination of the sensitivity to antibiotics was carried out using a BD Phoenix semiautomatic bacterial analyzer (United States), and manually to ceftaroline. Whole genome sequencing was performed on the Illumina HiSeq 2500 platform. Data processing and analysis were performed using the following resources: CLC Genomics Workbench, SPAdes, RAST Server, NCBI Prokaryotic Genome Annotation Pipeline, PlasmidFinder, Phaster, BLASTp NCBI, and OrthoMCL. The main characteristics of the SA943 genome, including clusters of resistance genes, factors of pathogenicity, adhesion, invasion, and regulation, were revealed. When analyzing the genome structure, the closest similarity to the representatives of the Eurasian ST239 subclone identified in Turkey, as well as a number of differences from 16K and OC3 strains isolated in Russia earlier, were noted. A unique SSR sequence of the spa gene, which was placed into the database as a new spa type t‑18470, was identified. Substitutions in the amino acid sequence of the gene products of the mec complex, ccrC recombinase, and PBP2 protein, which distinguish SA943 from most ST239 representatives, were revealed. Representatives of several ST239 subclones, including ceftaroline-resistant SA943 belonging to the Eurasian subclone, were identified in hospitals of the Russian Federation. The Eurasian subclone representatives are not a homogeneous group, but differ significantly in the structure of SCCmec and mutations in key antibiotic resistance genes. Whole genome sequencing not only allows one to reveal the features of genome microevolution of epidemic strains in distinct regions, but also to improve the quality of epidemiological analysis and to optimize infection control measures.