PURPOSE: Recent research shows an increasing recognition that organisms not traditionally considered infectious in nature contribute to disease processes. Propionibacterium acnes (P. acnes) is a gram-positive, aerotolerant anaerobe prevalent in the sebaceous gland-rich areas of the human skin. A ubiquitous slow-growing organism with the capacity to form biofilm, P. acnes, recognized for its role in acne vulgaris and medical device-related infections, is now also linked to a number of other human diseases. While bacterial culture and molecular techniques are used to investigate the involvement of P. acnes in such diseases, definitive demonstration of P. acnes infection requires a technique (or techniques) sensitive to the presence of biofilms and insensitive to the presence of potential contamination. Fortunately, there are imaging techniques meeting these criteria, in particular, fluorescence in situ hybridization and immunofluorescence coupled with confocal laser scanning microscopy, as well as immunohistochemistry. METHODS: Our literature review considers a range of microscopy-based studies that provides definitive evidence of P. acnes colonization within tissue from a number of human diseases (acne vulgaris, degenerative disc and prostate disease and atherosclerosis), some of which are currently not considered to have an infectious etiology. RESULTS/CONCLUSION: We conclude that P. acnes is an opportunistic pathogen with a likely underestimated role in the development of various human diseases associated with significant morbidity and, in some cases, mortality. As such, these findings offer the potential for new studies aimed at understanding the pathological mechanisms driving the observed disease associations, as well as novel diagnostic strategies and treatment strategies, particularly for degenerative disc disease. These slides can be retrieved under Electronic Supplementary Material.

Central European Institute of Technology Masaryk University Kamenice 753 5 625 00 Brno Czech Republic

Department of Biological Sciences and Binghamton Biofilm Research Center Binghamton University Binghamton NY USA

Department of Biomedicine Aarhus University Aarhus Denmark

Department of Microbiology Faculty of Medicine St Anne's University Hospital Masaryk University Brno Czech Republic

Department of Orthopedic Surgery Spine Unit Rigshospitalet University of Copenhagen Copenhagen Denmark

Department of Orthopedic Surgery University Southern California Los Angeles CA USA

Department of Orthopedics Physical Medicine and Rehabilitation University of Munich Munich Germany

Department of Pathology Microbiology and Immunology School of Medicine Vanderbilt University Nashville TN USA

Laboratory of Bacterial Pathogenesis and Immunology Rockefeller University 1230 York Avenue New York NY USA

Marian University Osteopathic Medical School Indianapolis IN USA

Northern Ireland Centre for Stratified Medicine School of Biomedical Sciences Ulster University Londonderry United Kingdom

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