Genetic determinants of antimicrobial resistance in three multi-drug resistant strains of Cutibacterium acnes isolated from patients with acne: a predictive in silico study

Objectives. Using available whole genome data, the objective of this in silico study was to identify genetic mechanisms that could explain the antimicrobial resistance profile of three multi-drug resistant (MDR) strains (CA17, CA51, CA39) of the skin bacterium Cutibacterium acnes previously recovered from patients with acne. In particular, we were interested in detecting novel genetic determinants associated with resistance to fluoroquinolone and macrolide antibiotics that could then be confirmed experimentally. Methods. A range of open source bioinformatics tools were used to ‘mine’ genetic determinants of antimicrobial resistance and plasmid borne contigs, and to characterise the phylogenetic diversity of the MDR strains. Results. As probable mechanisms of resistance to fluoroquinolones, we identified a previously described resistance associated allelic variant of the gyrA gene with a ‘deleterious' S101L mutation in type IA₁ strains CA51 (ST1) and CA39 (ST1), as well as a novel E761R ‘deleterious’ mutation in the type II strain CA17 (ST153). A distinct genomic sequence of the efflux protein YfmO which is potentially associated with resistance to MLSB antibiotics was also present in CA17; homologues in CA51, CA39, and other strains of Cutibacterium acnes, were also found but differed in amino acid content. Strikingly, in CA17 we also identified a circular 2.7 kb non-conjugative plasmid (designated pCA17) that closely resembled a 4.8 kb plasmid (pYU39) from the MDR Salmonella enterica strain YU39. Conclusions. This study has provided a detailed explanation of potential genetic determinants for MDR in the Cutibacterium acnes strains CA17, CA39 and CA51. Further laboratory investigations will be required to validate these in silico results, especially in relation to pCA17.