RESUMO
Selective pressure of beta-lactams is thought to be responsible for mutation selection in methicillin-susceptible Staphylococcus aureus (MSSA). We used next-generation sequencing to compare the genomes of beta-lactamase-positive (SA0707) and -negative (SA0937) MSSA isolates with their derivatives obtained after selection with oxacillin, ceftaroline, or meropenem. Selection with oxacillin and ceftaroline caused a rapid and significant (6-8 times) increase in the minimum inhibitory concentration (MICs) of oxacillin, penicillin, amoxicillin/clavulanate, and ceftaroline against the derivatives of both isolates, associated with growth impairment. Selection with meropenem caused a limited increase in the MICs of all beta-lactams against both isolates. During the initial stages of selection (after 5-15 passages), mutations were detected only in some reads, which indicated the heterogeneity of the population; however, during the later stages, either the population reversed to the wild type or fixation of the mutation was observed in the entire population. Selection with different beta-lactams caused diverse mutational events, but common mutations were detected in gdpP, all penicillin-binding proteins, cell wall regulators (vraST, graR), and deletions in the promoter region of pbp4. Therefore, the disk diffusion test with cefoxitin does not reveal resistance associated with these mechanisms in some cases, which can lead to the failure of beta-lactam therapy.
RESUMO
In this study, we identified the relationship between the genetic lineage of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) sequence type 22 (ST22) from Russia and other regions. Sixty ST22 isolates from Russia were characterised through whole-genome sequencing. To evaluate the phylogenetic relationship of Russian isolates with the global ST22 population, we analysed 1283 genomes obtained from NCBI's GenBank. The phylogenetic tree of the ST22 global population consisted of three main clusters (A, B and C). The first (cluster A) was represented by EMRSA-15 isolates, the second (cluster B) by heterogeneous isolates from different regions harbouring different sets of virulence genes, and the third (cluster C) by isolates from the Middle East previously recognised as 'Gaza clone' and similar isolates from Russia. Presence of the toxic shock syndrome toxin (tsst) and elastin-binding protein S (ebpS) genes as well as the hypothetical proteins NCTC13616_00051 and NCTC13616_00047 were the most useful factors in discriminating ST22 lineages. Although the CA-MRSA 'Gaza clone' was mainly recovered from carriers, its widespread occurrence is a cause for concern. Differentiation of the 'Gaza clone' from other MRSA lineages is necessary for planning infection control measures.