In it together: Candida-bacterial oral biofilms and therapeutic strategies

Abstract

Under natural environmental settings or in the human body, the majority of microorganisms exist in complex polymicrobial biofilms adhered to abiotic and biotic surfaces. These microorganisms exhibit symbiotic, mutualistic, synergistic, or antagonistic relationships with other species during biofilm colonization and development. These polymicrobial interactions are heterogeneous, complex and hard to control, thereby often yielding worse outcomes than monospecies infections. Concerning fungi, Candida spp., in particular, Candida albicans is often detected with various bacterial species in oral biofilms. These Candida-bacterial interactions may induce the transition of C. albicans from commensal to pathobiont or dysbiotic organism. Consequently, Candida-bacterial interactions are largely associated with various oral diseases, including dental caries, denture stomatitis, periodontitis, peri-implantitis, and oral cancer. Given the severity of oral diseases caused by cross-kingdom consortia that develop hard-to-remove and highly drug-resistant biofilms, fundamental research is warranted to strategically develop cost-effective and safe therapies to prevent and treat cross-kingdom interactions and subsequent biofilm development. While studies have shed some light, targeting fungal-involved polymicrobial biofilms has been limited. This mini-review outlines the key features of Candida-bacterial interactions and their impact on various oral diseases. In addition, current knowledge on therapeutic strategies to target Candida-bacterial polymicrobial biofilms is discussed.

Figure 1.

Association of Candida albicans and various bacteria in oral diseases. A variety of gram-positive and -negative oral bacteria interact with C. albicans, contributing to virulences of diverse oral diseases ranging from dental caries to oral cancer.

Figure 2.

Representative confocal images of C. albicans-S. mutans, C. albicans-S. gordonii, and C. albicans-S. mutans–S. gordonii biofilms cultured in media supplemented with 1% sucrose. Gray, green, red, and blue colors indicate C. albicans, S. mutans, S. gordonii, and extracellular polysaccharides (EPS)-matrix, respectively. Adapted with permission from Wan et al. (2021) Cross-Kingdom Cell-to-Cell Interactions in Cariogenic Biofilm Initiation. Journal of Dental Research, Vol. 100(1) 74–81. Copyright © International & American Associations for Dental Research 2020

Figure 3.

Various antibiofilm strategies to eradicate Candida-bacterial cross-kingdom biofilm. It includes but is not limited to naturally derived bioactive molecules, chemically synthesized compounds, nano-formulated drugs, and alternative biofilm treatment strategies. ROS denotes reactive oxygen species.