Understanding a cutibacterium adaptation to life on humans may help identify infections.

Summary: Abstract Body: Over one million indwelling medical device infections occur annually in the USA. Most are due to microbes that live on humans, like Cutibacterium acnes. This microbe is the most common cause of shoulder prosthesis infection and a common cause of neurosurgical shunt infections. C. acnes infections are frequently missed and strategies to quickly identify them are needed. C. acnes secretes the protein RoxP, which might be able to be used as a biomarker to identify these infections. Cutibacteria highly conserve roxP, which is not found in any other genera. Ancestral Propionibacteriaceae acquired this gene after they adapted to human skin, and it is only present in Cutibacterium acnes, modestum, and namnetense. C. acnes requires roxP for wild-type aerobic growth and human skin colonization. Since a better understanding of this protein could improve clinical care and our understanding of host-microbe interactions on human skin, we performed an in-depth analysis of RoxP. In this study, we assessed RoxP sequence space, identified orthologs, biochemically characterized the dominant ortholog, performed in silico analysis that identified conserved molecular surfaces, evaluated conserved surface features in functional experiments, generated anti-RoxP antibodies, and developed anti-RoxP immunoassays. One of these assays is a sandwich enzyme-linked immunosorbent assay (sELISA) with sub-nanogram sensitivity that can detect RoxP in human biofluids (serum, synovial fluid, cerebrospinal fluid) and C. acnes culture media. This sELISA is a promising tool for clinicians who may be able to use it on readily-available clinical samples to rapidly identify C. acnes infections. In addition, the use of this study's findings and assays in future work will help provide new insights into C. acnes biology and Cutibacterium evolution, thereby expanding our understanding of this skin commensal and part-time opportunistic pathogen. Md Shafiuddin¹, Wen-chi Huang¹, Gabriel Prather¹, Jeffrey Anton¹, Andrew Martin¹, Sydney Sillart¹, Jonathan Tang¹, Michael Vittori¹, Mike Prinsen¹, Jessica Ninneman¹, Chandra Manithody¹, Jeffrey Henderson¹, Alexander Aleem¹, Maxene Ilagan¹, William H. McCoy¹ 1. Medicine, Washington University in St Louis School of Medicine, St. Louis, MO, United States. Innate Immunity, Microbiology, and Microbiome