Extracellular vesicles from Cutibacterium acnes phylotypes IA1, IB, II and III, which contain glucoglycerolipids, are not cytotoxic but induce a strong pro-inflammatory response in human prostate epithelial and fibroblast cells

Abstract

Cutibacterium acnes represents one of the predominant bacterial taxa colonizing human skin. Its impact on host physiology is strongly phylotype-dependent: certain phylotypes are associated with the initiation and progression of acnes lesions, whereas others contribute to the stability and homeostasis of the cutaneous microbiota. Moreover, phylotype II C. acnes has been increasingly implicated in the etiology of chronic prostatitis, suggesting a broader pathogenic potential. The growing incidence of antimicrobial resistance in C. acnes underscores the need to identify novel antigenic determinants and molecular candidates for next-generation vaccine strategies. Notably, C. acnes , like many Gram-positive bacteria, produces extracellular vesicles (EVs) that function as carriers of enzymes, metabolites, immunogenic components and lipid structures. In the present study, four glycolipids (GL1–GL4) isolated from distinct C. acnes phylotypes were subjected to comprehensive structural characterization using GLC-MS, MALDI-TOF MS and NMR spectroscopy. These GL1-GL4 compounds are glycoglycerolipids composed of one or two glucose residues, a glycerol moiety and different numbers of fatty acid residues (mainly 15:0–18:0). The presence of GL1 within EVs fractions obtained from four C. acnes phylotypes has been confirmed. Subsequently, the effects of EVs and the glycolipids GL1 and GL3 on the viability of human prostate epithelial and fibroblast cell lines were assessed. None of the tested preparations exhibited significant cytotoxicity. However, EVs derived from phylotypes IA1 and II elicited markedly elevated release of IL-6 and TNF-α, demonstrating their substantial pro-inflammatory capacity and supporting their potential role in host-pathogen interactions.