Synergistic Interaction between Candida albicans and Commensal Oral Streptococci in a Novel In Vitro Mucosal Model

Candida albicans is a commensal colonizer of the gastrointestinal tract of humans, where it coexists with highly diverse bacterial communities. It is not clear whether this interaction limits or promotes the potential of C. albicans to become an opportunistic pathogen. Here we investigate the interaction between C. albicans and three species of streptococci from the viridans group, which are ubiquitous and abundant oral commensal bacteria. The ability of C. albicans to form biofilms with Streptococcus oralis, Streptococcus sanguinis, or Streptococcus gordonii was investigated using flow cell devices that allow abiotic biofilm formation under salivary flow. In addition, we designed a novel flow cell system that allows mucosal biofilm formation under conditions that mimic the environment in the oral and esophageal mucosae. It was observed that C. albicans and streptococci formed a synergistic partnership where C. albicans promoted the ability of streptococci to form biofilms on abiotic surfaces or on the surface of an oral mucosa analogue. The increased ability of streptococci to form biofilms in the presence of C. albicans could not be explained by a growth-stimulatory effect since the streptococci were unaffected in their growth in planktonic coculture with C. albicans. Conversely, the presence of streptococci increased the ability of C. albicans to invade organotypic models of the oral and esophageal mucosae under conditions of salivary flow. Moreover, characterization of mucosal invasion by the biofilm microorganisms suggested that the esophageal mucosa is more permissive to invasion than the oral mucosa. In summary, C. albicans and commensal oral streptococci display a synergistic interaction with implications for the pathogenic potential of C. albicans in the upper gastrointestinal tract.