Pathogenic genetic variations of C. acnes are associated with clinically relevant orthopedic shoulder infections

Abstract

Many surgeons continue to face the clinical dilemma of interpreting a positive aspiration or unexpected positive Cutibacterium acnes (C. acnes) culture. There are factors that complicate the interpretation of positive cultures including variations in both frequency of false positive cultures and virulence properties. As indices of virulence, hemolytic strains, from previously confirmed clinically infected shoulders, were compared with non-hemolytic isolates determined to be contaminants, by RNA-sequencing (RNA-Seq). Six C. acnes isolates from patients who underwent revision total shoulder arthroplasty (TSA) were identified based on previously described infection criteria. Three C. acnes isolates from each group underwent RNA-Seq. Differential gene expression analysis, principal component analysis (PCA), and heatmap analysis were used to determine the gene variation and patterning between the definite infection and probable contaminant isolates. Differential gene expression analysis identified genes that were differentially expressed between the isolates classified as definite infection and isolates classified as probable contaminants. PCA using a 500 gene subset of identified genes was able to find combinations of these genes that separated out the definite infection and probable contaminants isolates. The heatmap demonstrated similar gene expression in the three Definite Infections isolates, and significantly different expression when compared with the probable contaminant isolates. Clinical significance: C. acnes revision TSA isolates classified as definite infection and probable contaminant demonstrated a similar gene expression pattern to each respective group and different gene expression pattern when compared between groups. These findings indicate distinct differences in C. acnes strains associated with clinically relevant orthopedic TSA infections.

Keywords: Cutibacterium acnes; Propionibacterium acnes; RNA-Seq; gene expression analysis; periprosthetic joint infection; shoulder arthroplasty; shoulder infection.