Comparative genomics of phenotypic antimicrobial resistances in methicillin-resistant Staphylococcus pseudintermedius of canine origin.

Staphylococcus pseudintermedius is an important pathogen in dogs. Since 2004, methicillin- resistant S. pseudintermedius (MRSP) isolates, often multidrug resistant, have been observed in dogs in the Netherlands. This study aims to link the observed resistance phenotypes in canine MRSP to genotypic antimicrobial resistance markers, and to study the phylogeny of MRSP by genomic comparisons. The genomes of fifty clinical isolates of MRSP from dogs from the Netherlands were sequenced. The resistance genes were identified, and for twenty one different antimicrobials their presence and sequence were associated with the resistance phenotypes. In case of observed discrepancies, the genes were aligned with reference genes. Of the phenotypic resistances, 98.3% could be explained by the presence of an associated resistance gene or point mutation. Discrepancies were mainly resistance genes present in susceptible isolates; 43.8% (7/16) were explained by an insertion, deletion or mutation in the gene. In relation with the resistance gene presence or absence, a single-nucleotide polymorphism (SNP) based phylogeny was constructed to define the population dynamics. The resistance gene content differed according to clonal complex, from very conserved (CC45), to partly conserved (CC71) to highly diverse (CC258) resistance gene patterns. In conclusion, this study shows that the antimicrobial genotype from whole genome sequencing is highly predictive of the resistance phenotype in MRSP. Interestingly, the observed clonal complexes of MRSP isolates were linked with resistance gene patterns.