Evaluation of within-host evolution of methicillin-resistant Staphylococcus aureus (MRSA) by comparing cgMLST and SNP analysis approaches

Whole genome sequencing (WGS) of methicillin-resistant Staphylococcus aureus (MRSA) provides high-resolution typing, facilitating surveillance and outbreak investigations. The aim of this study was to evaluate the genomic variation rate in MRSA, by comparing commonly used core genome multilocus sequencing (cgMLST) against single nucleotide polymorphism (SNP) analyses. WGS was performed on 95 MRSA isolates, collected from 20 carriers during years 2003-2019. To assess variation and methodological-related differences, two different cgMLST schemes were obtained using Ridom SeqSphere+ and the cloud-based 1928 platform. In addition, two SNP methods, 1928 platform and Northern Arizona SNP Pipeline (NASP) were used. The cgMLST using Ridom SeqSphere+ and 1928 showed a median of 5.0 and 2.0 allele variants/year, respectively. In the SNP analysis, performed with two reference genomes COL and Newman, 1928 showed a median of 13 and 24 SNPs (including presumed recombination) and 3.8 respectively 4.0 SNPs (without recombination) per individual/year. Accordantly, NASP showed a median of 5.5 and 5.8 SNPs per individual/year. In conclusion, an estimated genomic variation rate of 2.0-5.8 genetic events per year (without recombination), is suggested as a general guideline to be used at clinical laboratories for surveillance and outbreak investigations independently of analysis approach used.