Inhibition of adhesive nanofibrillar mediated Streptococcus gordonii - Candida albicans mono- and dual-species biofilms

Dental caries and periodontitis are the most common oral disease of all age groups, affecting billions of people worldwide. These oral diseases are mostly associated with the microbial biofilms in the oral cavity. Streptococcus gordonii, an early tooth colonizing bacterium and Candida albicans, an opportunistic pathogenic fungus, are the two abundant oral microbes form mixed biofilms and augment their virulence properties affecting oral health negatively. Understanding the molecular mechanisms of their interactions and blocking the growth of these biofilms by nontoxic compounds could help develop effective therapeutic approaches. We report in this study, inhibition of mono- or dual-species biofilms of S. gordonii and C. albicans, and biofilm eDNA in vitro by Gymnemic Acids (GAs), a nontoxic small molecule inhibitor of fungal hyphae. Scanning electron microscopic images of biofilms revealed attachment of S. gordonii cells to the hyphal and on saliva-coated hydroxyapatite (sHA) surfaces via nanofibrils only in the untreated control but not in the GAs treated biofilms. Interestingly, C. albicans produced fibrillar adhesive structures from hyphae when grown with S. gordonii as mixed biofilm and addition of GAs to this biofilm abrogates the nanofibrils, reduces the growth of hyphae, and biofilms. To our knowledge, this is a first report that C. albicans produces adhesive fibrils from hyphae in response to S. gordonii mixed biofilm growth. A semi-quantitative PCR data of selected genes related to biofilms of both microbes show their differential expression. Further evaluation of one of the gene products of S. gordonii revealed that GAs could inhibit its recombinant glyceraldehyde-3-phosphate dehydrogenase (GAPDH) enzyme activity. Taken together, our results suggest that S. gordonii stimulates expression of adhesive materials in C. albicans by direct interaction and or by signaling mechanism(s), and these mechanisms can be inhibited by GAs. Further studies on global gene expression of these biofilms and their biochemical studies may reveal the molecular mechanism of their inhibition.