Genomics of Invasive Cutibacterium acnes Isolates from Deep-Seated Infections.

Cutibacterium acnes, formerly known as Propionibacterium acnes, is a commensal of the human pilosebaceous unit but also causes deep-seated infection, especially in the context of orthopedic and neurosurgical foreign materials. Interestingly, little is known about the role of specific pathogenicity factors for infection establishment. Here, 86 infection-associated and 103 commensalism-associated isolates of were collected from three independent microbiology laboratories. We sequenced the whole genomes of the isolates for genotyping and a genome-wide association study (GWAS). We found that subsp. IA was the most significant phylotype among the infection isolates (48.3% of all infection isolates; odds ratio [OR] = 1.98 for infection). Among the commensal isolates, subsp. IB was the most significant phylotype (40.8% of all commensal isolates; OR = 0.5 for infection). Interestingly, subsp. (III) was rare overall and did not occur at all in infection. The open reading frame-based GWAS (ORF-GWAS) did not show any loci with a strong signal for infection association (no values of ≤0.05 after adjustment for multiple testing; no logarithmic OR [logOR] of ≥|2|). We concluded that all subspecies and phylotypes of , possibly with the exception of subsp. , are able to cause deep-seated infection given favorable conditions, most importantly related to inserted foreign material. Genetic content appears to have a small effect on the likelihood of infection establishment, and functional studies are needed to understand the individual factors contributing to deep-seated infections caused by . Opportunistic infections emerging from human skin microbiota are of ever-increasing importance. Cutibacterium acnes, being abundant on the human skin, may cause deep-seated infections (e.g., device-associated infections). Differentiation between invasive (i.e., clinically significant) isolates and sole contaminants is often difficult. Identification of genetic markers associated with invasiveness not only would strengthen our knowledge related to pathogenesis but also could open ways to selectively categorize invasive and contaminating isolates in the clinical microbiology lab. We show that in contrast to other opportunistic pathogens (e.g., Staphylococcus epidermidis), invasiveness is apparently a broadly distributed ability across almost all subspecies and phylotypes. Thus, our work strongly supports an approach in which clinical significance is judged from clinical context rather than by detecting specific genetic traits.