Interaction of Cutibacterium (formerly Propionibacterium) acnes with bone cells: a step

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1 Title page Interaction of Cutibacterium (formerly Propionibacterium) acnes with bone cells: a step toward understanding bone and joint infection development Guillaume Ghislain Aubin,2 2 Bacteriology and Hygiene Unit, Nantes University Hospital, France. Marc Baud huin,4 4 Nantes University Hospital, Hôtel Dieu, Nantes, France. Jean-Philippe Lavigne 5,6 5 INSERM, U047, University of Montpellier, Nîmes, France. 6 Department of Microbiology, Caremeau University Hospital, Nîmes, France. Régis Brion,4 4 Nantes University Hospital, Hôtel Dieu, Nantes, France. François Gouin,7 7 Clinique chirurgicale orthopédique et traumatique, Nantes University Hospital, Nantes, France. Didier Lepelletier,2

2 MiHAR Lab, IRS2, 22 Bd 2 Bacteriology and Hygiene Unit, Nantes University Hospital, France. Cédric Jacqueline Dominique Heymann,4,8 4 Nantes University Hospital, Hôtel Dieu, Nantes, France. 8 Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK. Karim Asehnoune Stéphane Corvec,2,9* 2 Bacteriology and Hygiene Unit, Nantes University Hospital, France. 9 INSERM U892 - CNRS 6299 CRCNA Centre Régional en Cancérologie Nantes Angers - University of Nantes, Nantes, France. Team 2: Clinical and translational research in skin cancer.

3 Table Supplementary data. Cutibacterium acnes genomes overview Reference strain Strains KPA7202 (DSM 679) ATCC699 (DSM 897) BL Ntes HB Sequence type ST4 ST8 ST6 ST8 ST8 ST27 ST8 Clinical source contamination of an anaerobic culture Acne Hip arthroplasty Knee arthroplasty Acne Spine Spine Size (Mb) %GC Number of ORFs Number of RNAs Subsystem coverage (%) Number of subsystems Subsystem feature counts Cofactors, vitamins, prosthetic groups, pigments Cell wall and capsule Virulence, disease and defense 0 0 Potassium metabolism 9 4 Photosynthesis Miscellaneous Phages, prophages, transposable elements, plasmids Membrane transport Iron acquisition and metabolism RNA metabolism Nucleosides and nucleotides Protein metabolism Cell division and cell cycle Motility and chemotaxis 0 Regulation and cell signaling Secondary metabolism DNA metabolism Fatty acids, lipids, and isoprenoids Nitrogen metabolism Dormancy and sporulation Respiration Stress response Metabolism of aromatic compounds Amino acids and derivatives Sulfur metabolism 4 Phosphorus metabolism Carbohydrates

4 Table 2 supplementary data. Cutibacterium acnes gene comparison according to phenotypic features observed (bone cells internalization). Non-internalized strains specific genes Internalized strains specific genes Total 22 5 Not part of a subsystem Succinate dehydrogenase flavoprotein subunit Glucose Fructose oxidoreductase 4-hydroxyphenylpyruvate dioxygenase Gluconokinase Putative TraA-like conjugal transfer protein acetyltransferase, GNAT family Ornithine cyclodeaminase Streptomyces scabies esterase domain Conserved protein (DUF74) Thrombospondin repeat and PKD domain conjugal transfer protein (TraA-like protein) fragment ATP-dependent exodnase (exonuclease V), alpha subunit - helicase superfamily I member transfer protein homolog TraA conserved hypothetical protein (putative ATP-binding) Mobile element protein Lanthionine biosynthesis protein LanB Lantibiotic biosynthesis dihydropyridine synthase, TsrD family TIM-barrel signal transduction protein Transcriptional regulator protein of unknown function UPF026 Alpha-aspartyl dipeptidase Peptidase E Glycosyl hydrolase family protein Alpha-galactosidase Conserved protein Oligopeptide ABC transporter, periplasmic oligopeptide-binding

5 protein OppA Substrate-specific component BL0695 of predicted ECF transporter Transmembrane component BL0694 of energizing module of predicted ECF transporter *PSI-Blast iteration: No putative conserved domains have been detected

6 Video legend Cutibacterium acnes ATCC699 inside MG-6 osteoblast cell

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