AUTHOR=Khoury Zaid H. , Vila Taissa , Puthran Taanya R. , Sultan Ahmed S. , Montelongo-Jauregui Daniel , Melo Mary Anne S. , Jabra-Rizk Mary Ann 

TITLE=The Role of Candida albicans Secreted Polysaccharides in Augmenting Streptococcus mutans Adherence and Mixed Biofilm Formation: In vitro and in vivo Studies

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00307

DOI=10.3389/fmicb.2020.00307

ISSN=1664-302X

ABSTRACT=<p>The oral cavity is a complex environment harboring diverse microbial species that often co-exist within biofilms formed on oral surfaces. Within a biofilm, inter-species interactions can be synergistic in that the presence of one organism generates a niche for another enhancing colonization. Among these species are the opportunistic fungal pathogen <italic>Candida albicans</italic> and the bacterial species <italic>Streptococcus mutans</italic>, the etiologic agents of oral candidiasis and dental caries, respectively. Recent studies have reported enhanced prevalence of <italic>C. albicans</italic> in children with caries indicating potential clinical implications for this fungal-bacterial interaction. In this study, we aimed to specifically elucidate the role of <italic>C. albicans</italic>-derived polysaccharide biofilm matrix components in augmenting <italic>S. mutans</italic> colonization and mixed biofilm formation. Comparative evaluations of single and mixed species biofilms demonstrated significantly enhanced <italic>S. mutans</italic> retention in mixed biofilms with <italic>C. albicans.</italic> Further, <italic>S. mutans</italic> single species biofilms were enhanced upon exogenous supplementation with purified matrix material derived from <italic>C. albicans</italic> biofilms. Similarly, growth in <italic>C. albicans</italic> cell-free spent biofilm culture media enhanced <italic>S. mutans</italic> single species biofilm formation, however, the observed increase in <italic>S. mutans</italic> biofilms was significantly affected upon enzymatic digestion of polysaccharides in spent media, identifying <italic>C. albicans</italic> secreted polysaccharides as a key factor in mediating mixed biofilm formation. The enhanced <italic>S. mutans</italic> biofilms mediated by the various <italic>C. albicans</italic> effectors was also demonstrated using confocal laser scanning microscopy. Importantly, a clinically relevant mouse model of oral co-infection was adapted to demonstrate the <italic>C. albicans</italic>-mediated enhanced <italic>S. mutans</italic> colonization in a host. Analyses of harvested tissue and scanning electron microscopy demonstrated significantly higher <italic>S. mutans</italic> retention on teeth and tongues of co-infected mice compared to mice infected only with <italic>S. mutans</italic>. Collectively, the findings from this study strongly indicate that the secretion of polysacharides from <italic>C. albicans</italic> in the oral environment may impact the development of S. mutans biofilms, ultimately increasing dental caries and, therefore, <italic>Candida</italic> oral colonization should be considered as a factor in evaluating the risk of caries.</p>