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Fourier transform mid-infrared-attenuated reflectance spectroscopy analysis on Candida albicans structure and conformation during its yeast-to-hyphae transition and in response to isolated and synergistic phenolic acids
Candida albicans is often a commensal member of the mucosal flora but can cause life-threatening infection when the host immunity is compromised. The major problem in the management of C. albicans infection is the emergence of drug resistant strains to commonly used antifungal agents. Phenolic compounds have become candidates as alternative agents due to their antifungal ability, but the mechanism is largely unknown. C. albicans yeast-to-hyphae transition greatly attributes to its virulence and therefore, targeted inhibition of hyphae phenotype is an attractive option. The main objective of this work was to evaluate the synergistic potential of phenolic acids on preventing C. albicans yeast-to-hyphae transition with a focus on the understanding multi-targeted effect on the cell metabolism as monitored by Fourier transform mid infrared spectroscopy in attenuated total reflectance mode (FT-mIR-ATR). The hypothesis of this study was that selected phenolics in combination would be more effective in preventing the yeast-to-hyphae transition than as isolated components and in turn modulate structure and conformation on the cells. The feasibility of FT-mIR-ATR in monitoring the C. albicans yeast-to-hyphae transition using hydrated cell pellets was first evaluated. The spectral signatures indicating structural and compositional modification in cell main components including lipids, proteins, nucleotides and cell wall polysaccharides during the transition proved the instrumental sensitivity and provided a point of reference. C. albicans was then treated with phenolic compounds in isolation or in combination in a N-acetylglucosamine inducing media and the minimum concentrations necessary to inhibit 50% hyphal formation by 24 h (MIC50) were determined. Isobologram analyses confirmed that gallic (GA), ferulic (FA) and sinapic (SA) acids protected against hyphal formation synergistically. Finally, FT-mIR-ATR approach was applied to cells treated with FA and GA in isolation and in combination at MIC50. Spectral analysis revealed metabolic profiles that were unique to the treatments demonstrating that phenolics likely targeted multiple metabolic pathways to exert synergistic anti-hyphal ability. Overall, this work presented the synergistic effect of phenolic compounds on preventing C. albicans yeast-to-hyphae transition and extended the understanding of mechanisms underlying this phenomenon, which may contribute to the development of natural intervention for managing C. albicans infection.
Shi, Qin-Yin, "Fourier transform mid-infrared-attenuated reflectance spectroscopy analysis on Candida albicans structure and conformation during its yeast-to-hyphae transition and in response to isolated and synergistic phenolic acids" (2017). ETD collection for University of Nebraska - Lincoln. AAI10253988.