Contact-dependent interactions between Cutibacterium acnes and Staphylococcus lugdunensis promote biofilm matrix remodeling

Abstract Prosthetic joint infections (PJIs) pose a substantial burden to patients and healthcare systems. These infections are often persistent and frequently require revision procedures, increasing the risk of surgical failure and mortality. A major virulence determinant underlying their persistence is biofilm formation, which protects bacteria from antibiotic treatment and host immune defenses. Understanding the mechanisms that promote biofilm formation is therefore critical for improving PJI management. Staphylococcus spp. and Cutibacterium acnes are common skin commensals that are frequently co-isolated from chronic prosthetic device infections. We hypothesized that these organisms interact synergistically to enhance the persistence of polymicrobial infections. We found that C. acnes increases dual-species biofilm formation with Staphylococcus lugdunensis and Staphylococcus hominis relative to monocultures. This phenotype was specific to these species combinations and was widespread among the strains tested. To investigate the underlying mechanism, we focused on the interaction between C. acnes and S. lugdunensis . Enhanced biofilm formation required both species to be metabolically active and in direct physical contact. Notably, co-culture shifted S. lugdunensis biofilms from their typical proteinaceous matrix to a polysaccharide intercellular adhesin (PIA)-rich matrix. Consistent with this transition, co-culture with C. acnes significantly increased expression of icaA , a gene involved in PIA biosynthesis, while having no effect on expression of atlL and mgtE , genes associated with the proteinaceous matrix of S. lugdunensis . Together, these findings reveal a novel contact-dependent interspecies interaction in which C. acnes promotes a switch to PIA-mediated biofilm formation in S. lugdunensis , a mechanism that may enhance persistence on medical devices and contribute to chronic polymicrobial infections.