Synergistic effects of quorum-sensing molecules and antimicrobials against Candida albicans and Pseudomonas aeruginosa biofilms: in vitro and in vivo studies

Abstract

Abstract Background Candida albicans can form polymicrobial biofilms with other microorganisms, such as Pseudomonas aeruginosa, at infection sites. Objectives As biofilms are highly resistant to antibiotics there is a need for new antibiofilm agents that have unique targets and modes of action. Methods In this study the antibiofilm effects of two quorum-sensing molecules (QSMs), farnesol and tyrosol, were investigated alone and in combination with antibiotics (aztreonam, colistin, tobramycin) and antifungals (fluconazole, amphotericin B, caspofungin), against single- and dual-species biofilms of C. albicans and P. aeruginosa in in vitro and in vivo systems. Results It was observed that QSMs alone, especially farnesol, showed at least a 1-log reduction against preformed single- and dual-species biofilms of C. albicans and P. aeruginosa. Combination of QSMs with colistin or fluconazole was found to be effective against both single- and dual-species biofilms in vitro. Increased survival was observed in C. elegans when treated with colistin or fluconazole in combination with QSMs, compared with no treatment. Additionally, the QSMs and colistin and farnesol combinations effectively inhibited biofilm formation by C. albicans and P. aeruginosa on bronchial epithelial cells, and reduced IL-1β expression in lung bronchial epithelial cells. Conclusions There is a need for effective treatments for bacterial-fungal biofilm infections and, to our knowledge, there have been no studies of QSMs and antimicrobial combinations against dual-species biofilms involving C. albicans and P. aeruginosa. Hence these findings will make a significant contribution to the literature.