Candida albicans is an opportunistic fungal pathogen that is highly resistant to contemporary antifungals, and a major reason for this appears to be their predominant, filamentation-mediated, biofilm lifestyle. Hence, agents that inhibit biofilms and filamentation of the yeast offer promise as next-generation antifungals. Curcumin is a natural polyphenol with several beneficial pharmacological attributes, yet limitations such as poor solubility, acid, and enzyme tolerance have impeded its practical utility.Sophorolipids are biologically-derived surfactants that serve as efficient carriers and delivery agents of hydrophobic molecules, such as curcumin, into biofilms. The aim of this study was to investigate the effects of a novel, curcumin-sophorolipid (CU-ASL) nano-conjugate on Candida albicans biofilms and filamentation. The effects of CU and ASL, in combination, and alone, were investigated on planktonic cells of the yeast. The effects of sub-inhibitory concentrations of the compounds were investigated on biofilm biomass and biofilm architecture. Their effects on filamentation was compared by scanning electron microscopic imaging, and gene expression analysis by qRT-PCR.Our results demonstrated that sub-inhibitory concentration of CU-ASL (9.37 µg/mL) significantly inhibited candidal adhesion to substrates, and subsequent biofilm development, maturation, and filamentation. This effect was associated with significant downregulation of a select group of biofilm, adhesins, and hyphal regulatory genes. In conclusion, the curcumin-sophorolipid nano-conjugate is a potent inhibitor of the two major virulence attributes of C. albicans, biofilm formation and filamentation, thus highlighting its promise as a putative anti-candidal agent with low toxicity and biofilm penetrative potential..
We report a PL biosensor using cysteamine functionalized ZnO nanoparticles for the detection of quorum sensing signals (N-acyl homoserine lactones).
Candida albicans as an opportunistic pathogen exploits the host immune system and causes a variety of life-threatening infections. The polymorphic nature of this fungus gives it tremendous advantage to breach mucosal barriers and cause oral and disseminated infections. Similar to C. albicans, Enterococcus faecalis is a major opportunistic pathogen, which is of critical concern in immunocompromised patients. There is increasing evidence that E. faecalis co-exists with C. albicans in the human body in disease samples. While the interactive profiles between these two organisms have been studied on abiotic substrates and mouse models, studies on their interactions on human oral mucosal surfaces are non-existent. Here, for the first time, we comprehensively characterized the interactive profiles between laboratory and clinical isolates of C. albicans (SC5314 and BF1) and E. faecalis (OG1RF and P52S) on an organotypic oral mucosal model. Our results demonstrated that the dual species biofilms resulted in profound surface erosion and significantly increased microbial invasion into mucosal compartments, compared to either species alone. Notably, several genes of C. albicans involved in tissue adhesion, hyphal formation, fungal invasion, and biofilm formation were significantly upregulated in the presence of E. faecalis. By contrast, E. faecalis genes involved in quorum sensing, biofilm formation, virulence, and mammalian cell invasion were downregulated. This study highlights the synergistic cross-kingdom interactions between E. faecalis and C. albicans in mucosal tissue invasion.
Plants have always been a supreme source of drugs and India is endowed with a wide variety of them with high medicinal values. The Quorum Sensing (QS) quenching efficiency of various solvent extracts of Melia dubia seeds was investigated against uropathogenic Escherichia coli (UPEC) to screen the competitive inhibitor of SdiA, a transcriptional activator of quorum sensing in E. coli. In this study, potentiality of five different extracts of Melia dubia seeds for quorum sensing inhibitory activity was investigated against uropathogenic Escherichia coli (UPEC). Assays such as cell density, swarming motility, protein, protease, hemolysis, hemagglutination, hydrophobicity and biofilm inhibition were performed. Biofilm, hemolysis and swarming motility were found to be inhibited by 92.1%, 20.9 % and 48.52% respectively, when the medium was supplemented with 30 mg/ml of the ethanolic extract. GC-MS spectrum of the ethanolic extract showed an array of 27 structurally unlinked compounds with natural ligand C8HSL. The docking against QS transcriptional regulator SdiA was predicted by in silico studies and the ligand C6 showed significant activity with -10.8 GScore. In vitro and in silico docking analysis showed fairly a good correlation, suggesting that the ethanolic extract showed potency to attenuate quorum sensing of uropathogenic E. coli. Further studies by in vitro and in vivo strategies are necessary to foresee the quorum quenching effect of the ligands.
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