Andreas Podbielski ^1,2 Thomas Köller ^1,2 Philipp Warnke ^1,2 Walter Israel Barrantes Bustinza ^2,3 Bernd Kreikemeyer ^2,4*

• ¹ Institute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Rostock, Mecklenburg-Vorpommern, Germany
• ² University Hospital Rostock, Rostock, Mecklenburg-Vorpommern, Germany
• ³ Institute for Biostatistics and Informatics in Medicine and Ageing Research, University Hospital Rostock, Rostock, Mecklenburg-Vorpommern, Germany
• ⁴ Institute of Medical Microbiology, Virology and Hygiene,, University of Rostock, Rostock, Germany

Cutibacterium acnes can both be a helpful colonizer of the human skin as well as the causative agent of acne and purulent infections. Until today, it is a moot point whether there are C. acnes strains exclusively devoted to be part of the skin microbiome and others, that carry special features enabling them to cause disease. So far, the search for the molecular background of such diverse behavior has led to inconsistent results. In the present study, we prospectively collected C. acnes strains from 27 infected persons and 18 healthy controls employing rigid selection criteria to ensure their role as infectious agent or colonizer. The genome sequences from these strains were obtained and carefully controlled for quality. Deduced traditional phylotyping assigned almost all superficial isolates to type IA1, while the clinical strains were evenly distributed between types IA1, IB, and II. Single locus sequence typing (SLST) showed a predominance of A1 type for the control strains, whereas 56% of the clinical isolates belonged to types A1, H1 and K8. Pangenome analysis from all the present strains and 30 published genomes indicated the presence of an open pangenome. Except for three isolates, the colonizing strains clustered in clades separate from the majority of clinical strains, while 4 clinical strains clustered with the control strains. Identical results were obtained by a single nucleotide polymorphism (SNP) analysis. However, there were no significant differences in virulence gene contents in both groups. Genome-wide association studies (GWAS) from both the pangenome and SNP data consistently showed genomic differences between both groups located in metabolic pathway and DNA repair genes. Thus, the different behavior of colonizing and infectious C. acnes strains could be due to special metabolic capacities or flexibilities rather than specific virulence traits.