5-hydroxymethyl-2-furaldehyde impairs Candida albicans - Staphylococcus epidermidis interaction in co-culture by suppressing crucial supportive virulence traits.

Abstract

Polymicrobial biofilms involving fungal-bacterial interactions are stated to modulate host immune response and exhibit enhanced antibiotic resistance. In this milieu, clinically important opportunistic pathogens Candida albicans and Staphylococcus epidermidis associate synergistically and instigate implant and blood stream infections. Impediment of virulence traits that support successive pathogenic lifestyle and inter-kingdom interactions without altering the microbial growth represents an attractive alternate strategy. To accomplish this objective, 5-hydroxymethyl-2-furaldehyde (5HM2F), a reported antibiofilm agent against C. albicans, was considered for this study. 5HM2F significantly repressed the biofilm formation of S. epidermidis and mixed-species at 300\u202fμg/mL and 400\u202fμg/mL, respectively without modulating the growth. Microscopic analyses and phenotypic assays explicated the competency of 5HM2F to impede biofilm formation, hyphal growth, initial attachment, intercellular adhesion, and fungal-bacterial interaction. Further, 5HM2F greatly reduced the secreted hydrolases production. Reduced content of biofilm matrix components upon 5HM2F treatment was believed to be the underlying reason for enhanced antibiotic and/antifungal susceptibility. Additionally, qPCR analysis correlated well with in vitro bioassays wherein, 5HM2F was identified to repress the expression of important genes associated with hyphal morphogenesis, adhesion, biofilm formation and virulence in both mono-species and mixed-species. Reduced virulence and colonization of mono-species and mixed-species in 5HM2F treated Caenorhabditis elegans substantiated the antibiofilm and antivirulence potential of 5HM2F. Overall, this study proposes 5HM2F as a potent therapeutic candidate against single and mixed-species biofilm infections of C. albicans and S. epidermidis.