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

Abstract

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.

Competitive inter-species interactions underlie the increased antimicrobial tolerance in multispecies brewery biofilms

“…Some of the bacterial species 531 experienced a reduced growth due to competition in the untreated multispecies biofilm, while 532 antimicrobial treatment restored their growth in the multispecies biofilm to the level of the untreated 533 monoculture biofilms. In contrast, but also consistent with our rationale, a reduction in antimicrobial 534 tolerance under multispecies conditions has been explicitly associated with a reduction of (probably 535 rare) cooperative inter-species interactions (Feldman et al, 2016). 536 In our final model, we found that the presence of competitors can also directly enhance the 537 inherent tolerance of other species by driving specific tolerance phenotypes.…”

“…Indeed, incomplete 496 inhibition of a network of cooperating species is expected, not to promote, but to pull down the 497 remaining species because of abrogation of positive feedback loops, as is motivated by recent 498 ecological network studies (Coyte et al, 2015). This would reduce, not increase, the overall tolerance 499 of the multispecies biofilm (Feldman et al, 2016). Our models only provide examples of multispecies 500 biofilms in which specific species strongly suppress other species.…”

“…In most of these studies the enhanced tolerance was attributed to 487 protective effects of the species on each other, however, generally without unraveling the mechanism 488 of tolerance. In contrast, a minority of studies did not observe an effect of multispecies conditions on 489 antimicrobial tolerance (Gkana et al, 2017) or did even measure a decrease in tolerance in 490 multispecies conditions (Lindsay et al, 2002;Chorianopoulos et al, 2008;Kart et al, 2014;Yassin et 491 al., 2016;Feldman et al, 2016). 492…”

Competitive inter-species interactions underlie the increased antimicrobial tolerance in multispecies brewery biofilms

“…Indeed, incomplete inhibition of a network of cooperating species is expected, not to promote, but to pull down the remaining species because of abrogation of positive feedback loops, as is indicated by recent ecological network studies [84]. This would reduce, not increase, the overall tolerance of the multispecies biofilm [80]. Our models only provide examples of duo-species or multispecies biofilms in which specific species strongly suppress other species.…”

“…In most of these studies the enhanced tolerance was attributed to protective effects of the species on each other, however, generally without unraveling the mechanism of tolerance. In contrast, a minority of studies did not observe an effect of multispecies conditions on antimicrobial tolerance [79] or measured a decrease in tolerance in multispecies conditions [63,[80][81][82][83].…”