Feldman Mark, Ginsburg Isaac, Al-Quntar Abed, Steinberg Doron
Biofilm Research Laboratory, Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem Jerusalem, Israel.
Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem Jerusalem, Israel.
Front Microbiol. 2016 Feb 10;7:140. doi: 10.3389/fmicb.2016.00140. eCollection 2016.
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.
小分子噻唑烷二酮 - 8（S - 8）已被证明可抑制多种微生物病原体的生物膜形成，包括白色念珠菌和变形链球菌。此前，我们已经评估了S - 8针对白色念珠菌生物膜相关致病性的具体分子作用模式。在本研究中，我们调查了S - 8对白色念珠菌 - 变形链球菌双物种生物膜的影响。我们发现，在S - 8存在的情况下，双物种生物膜形成减少，对白色念珠菌有主要影响。S - 8显著降低了生物膜生物量和胞外多糖（EPS）的产生。此外，该药物引起氧化应激，伴有活性氧的强烈诱导以及混合生物膜对过氧化氢摄取的抑制。此外，S - 8通过复杂机制改变了这些物种之间的共生关系。与群体感应（QS）相关的链球菌基因（comDE和luxS）、EPS产生相关基因（gtfBCD和gbpB）以及与抗氧化应激相关的基因（nox和sodA）被S - 8显著上调。相反，在S - 8存在的情况下，与菌丝形成（hwp1）、粘附（als3）、疏水性（csh1）以及氧化应激反应相关的真菌基因（sod1、sod2和cat1）被下调。此外，与白色念珠菌酵母形态相关的ywp1基因被S - 8诱导，这与S - 8处理的双物种生物膜中大多为酵母细胞的出现相关。我们得出结论，S - 8扰乱了双物种生物膜中白色念珠菌和变形链球菌之间的共生平衡。
