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The small molecule, thiazolidinedione-8 (S-8) was shown to impair biofilm formation of various microbial pathogens, including the fungus  Candida albicans  and  Streptococcus mutans . Previously, we have evaluated the specific molecular mode of S-8 action against  C. albicans  biofilm-associated pathogenicity. In this study we investigated the influence of S-8 on dual species,  C. albicans-S. mutans  biofilm. We show that in the presence of S-8 a reduction of the co-species biofilm formation occurred with a major effect on  C. albicans . Biofilm biomass and exopolysaccharide (EPS) production were significantly reduced by S-8. Moreover, the agent caused oxidative stress associated with a strong induction of reactive oxygen species and hydrogen peroxide uptake inhibition by a mixed biofilm. In addition, S-8 altered symbiotic relationship between these species by a complex mechanism. Streptococcal genes associated with quorum sensing (QS) ( comDE  and  luxS ), EPS production ( gtfBCD  and  gbpB ), as well as genes related to protection against oxidative stress ( nox  and  sodA ) were markedly upregulated by S-8. In contrast, fungal genes related to hyphae formation ( hwp1 ), adhesion ( als3 ), hydrophobicity ( csh1 ), and oxidative stress response ( sod1 ,  sod2 , and  cat1 ) were downregulated in the presence of S-8. In addition,  ywp1  gene associated with yeast form of  C. albicans  was induced by S-8, which is correlated with appearance of mostly yeast cells in S-8 treated dual species biofilms. We concluded that S-8 disturbs symbiotic balance between  C. albicans  and  S. mutans  in dual species biofilm.

Thiazolidinedione-8 Alters Symbiotic Relationship in C. albicans-S. mutans Dual Species Biofilm