Interkingdom Biofilms in Chronic Wounds: The Collaboration of Candida albicans and Staphylococcus aureus Against Conventional Wound Antiseptics in a Wound-like Leucocyte-Rich Human Plasma Biofilm Model (lhBIOM)

Background: Chronic wounds are frequently associated with biofilms, in which not only bacterial but also fungal pathogens can impair wound healing. Among the most relevant opportunistic pathogens is Staphylococcus aureus; together with Candida albicans, both are part of the human skin microbiome but can also colonize chronic wounds. Interkingdom biofilms formed by these microorganisms have been shown to exacerbate the course of diseases compared to infections caused by either species alone. Methods: To address the limited number of studies examining fungal–bacterial interactions in wound environments, leucocyte-rich human plasma biofilm models (lhBIOMs) inoculated with S. aureus and C. albicans were prepared. The efficacy of the commonly used clinical antiseptics octenidine dihydrochloride/phenoxyethanol (OCT/PE) and polyhexamethylene biguanide (PHMB) was examined using the quantitative suspension method (QSM). In addition, spatial distribution and morphology of the microorganisms within this biofilm model were analyzed by confocal laser scanning microscopy (CLSM). Results: In this study, the presence of S. aureus triggered an increase in the formation of filamentation of C. albicans in contrast to the single-species biofilm. In addition, treatment with the tested antimicrobial agents was effective against C. albicans after repetitive applications and showed a clear reduction against S. aureus. Furthermore, the quantitative analysis of the co-culture revealed increased growth of S. aureus in the control culture compared to the single-species model. Conclusions: These findings highlight the pathogenic relevance of interkingdom biofilms in chronic wounds and emphasize the importance of effective species-independent antimicrobial treatment strategies.