In recent decades, fungal infections have incredibly increased with Candida genus as the major cause of morbidity and mortality in hospitalized and immunocompromised patients. Most of the Candida species are proficient in biofilm formation on implanted medical devices as well as human tissues. Biofilm related Candida infections are very difficult to treat using common antifungal agents owing to their increased drug resistance. To address these issues, the present study investigated the antibiofilm and antivirulent properties of Syzygium cumini derived quinic acid in combination with known antifungal compound undecanoic acid. Initially, antibiofilm potential of S. cumini leaf extract was assessed and the active principles were identified through gas chromatography and mass spectrometry analysis. Among the compounds identified, quinic acid was one of the major compounds. The interaction between quinic acid and undecanoic acid was found to be synergistic in the Fractional inhibitory concentration index (≤0.5). Results of in vitro assays and gene expression analysis suggested that the synergistic combinations of quinic acid and undecanoic acid significantly inhibited virulence traits of Candida spp. such as the biofilm formation, yeast-to-hyphal transition, extracellular polymeric substances production, filamentation, secreted hydrolases production and ergosterol biosynthesis. In addition, result of in vivo studies using Caenorhabditis elegans demonstrated the non-toxic nature of QA-UDA combination and antivirulence effect against Candida spp. For the first time, synergistic antivirulence ability of quinic acid and undecanoic acid was explored against Candida spp. Thus, results obtained from the present study suggest that combination of phytochemicals might be used an alternate therapeutic strategy for the prevention and treatment of biofilm associated Candida infection.

Curcumin, a yellow-colored molecule derived from the rhizome of Curcuma longa, has been identified as the bioactive compound responsible for numerous pharmacological activities of turmeric, including anticancer, antimicrobial, anti-inflammatory, antioxidant, antidiabetic, etc. Nevertheless, the clinical application of curcumin is inadequate due to its low solubility, poor absorption, rapid metabolism and elimination. Advancements in recent research have shown several components and techniques to increase the bioavailability of curcumin. Combining with adjuvants, encapsulating in carriers and formulating in nanoforms, in combination with other bioactive agents, synthetic derivatives and structural analogs of curcumin, have shown increased efficiency and bioavailability, thereby augmenting the range of applications of curcumin. The scope for incorporating biotechnology and nanotechnology in amending the current drawbacks would help in expanding the biomedical applications and clinical efficacy of curcumin. Therefore, in this review, we provide a comprehensive overview of the plethora of therapeutic potentials of curcumin, their drawbacks in efficient clinical applications and the recent advancements in improving curcumin’s bioavailability for effective use in various biomedical applications.

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Candida species are opportunistic fungal pathogens, which are known for their biofilm associated infections on implanted medical devices in clinical settings. Broad spectrum usage of azole groups and other antifungal agents leads to the occurrence of drug resistance among Candida species. Most of the antifungal agents have failed to treat the biofilm mediated Candida infections. In the present study, silver nanoparticles (AgNPs) were synthesized using Dodonaea viscosa and Hyptis suoveolens methanolic leaf extracts and characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction analysis, Fourier transform infrared spectroscopy and Scanning electron microscopy, Dynamic light scattering, and Zeta potential analysis. The main goal of this study was to assess the AgNPs for their antibiofilm efficacy against Candida spp. through microscopic analysis and in vitro virulence assays. The results revealed that AgNPs strongly inhibited more than 80% biofilm formed by Candida spp. Furthermore, the AgNPs also reduced the yeast-to-hyphal transition, exopolysaccharide biosynthesis, secreted aspartyl proteinase production which are the major virulence factors of Candida species. This study reveals that biosynthesized AgNPs can be considered for the treatment of biofilm related Candida infections.

Metabolomic reprogramming plays a crucial role in the activation of several regulatory mechanisms including neuronal responses of the host. In the present study, alterations at physiological and biochemical levels were initially assessed to monitor the impact of the candidate pathogen Cronobacter sakazakii on the nematode host Caenorhabditis elegans. The abnormal behavioral responses were observed in infected worms in terms of hyperosmolarity and high viscous chemicals. The microscopic observations indicated reduction in egg laying and internal hatching of larvae in the host. An increased level of total reactive oxygen species and reduction in antioxidant agents such as glutathione and catalase were observed. These observations suggested the severe effect of C. sakazakii infection on C. elegans. To understand the small molecules which likely mediated neurotransmission, the whole metabolome of C. elegans during the infection of C. sakazakii was analyzed using liquid chromatography−mass spectrometry. A decrease in the quantity of methyl dopamine and palmitoyl dopamine and an increase in hydroxyl dopamine suggested that reduction in dopamine reuptake and dopamine neuronal stress. The disordered dopaminergic transmission during infection was confirmed using transgenic C. elegans by microscopic observation of Dat-1 protein expression. In addition, reduction in arachidonic acid and short-chain fatty acids revealed their effect on lipid droplet formation as well as neuronal damage. An increase in the quantity of stearoyl CoA underpinned the higher accumulation of lipid droplets in the host. On the other hand, an increased level of metabolites such as palmitoyl serotonin, citalopram N-oxide, and N-acyl palmitoyl serotonin revealed serotonin-mediated potential response for neuroprotection, cytotoxicity, and cellular damage. Based on the metabolomic data, the genes correspond to small molecules involved in biosynthesis and transportation of candidate neurotransmitters were validated through relative gene expression.

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