Mechanistic Insights into the Anticandidal Action of Vanillin Reveal Disruption of Cell Surface Integrity and Mitochondrial Functioning

Abstract

<jats:sec> <jats:title>Background:</jats:title> <jats:p>Considering the emergence of multidrug resistance (MDR) in prevalent human fungal pathogen, Candida albicans, there is parallel spurt in development of novel strategies aimed to disrupt MDR. Compounds from natural resources could be exploited as efficient antifungal drugs owing to their structural diversity, cost effectiveness and negligible side effects.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p> The present study elucidates the antifungal mechanisms of Vanillin (Van), a natural food flavoring agent against Candida albicans.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p> Antifungal activities were assessed by broth microdilution and spot assays. Membrane and cell wall perturbations were studied by PI uptake, electron microscopy, plasma membrane H+ extrusion activity and estimation of ergosterol and chitin contents. Mitochondrial functioning was studied by growth on non-fermentable carbon sources, rhodamine B labeling and using retrograde signaling mutants. Gene expressions were validated by semi-quantitative RT-PCR.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> We observed that the antifungal activity of Van was not only limited to clinical isolates of C. albicans but also against non-albicans species of Candida. Mechanistic insights revealed effect of Van on cell surface integrity as evident from hypersensitivity against membrane perturbing agent SDS, depleted ergosterol levels, transmission electron micrographs and diminished plasma membrane H+ extrusion activity. In addition, spot assays with cell wall perturbing agents, scanning electron micrographs, delayed sedimentation rate and lower chitin content further substantiate cell wall damage by Van. Furthermore, Van treated cells underwent mitochondrial dysfunctioning via impaired retrograde signaling leading to abrogated iron homeostasis and DNA damage. All the perturbed phenotypes were also validated by RT-PCR depicting differential regulation of genes (NPC2, KRE62, FTR2 and CSM3) in response to Van.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Together, our results suggested that Van is promising antifungal agent that may be advocated for further investigation in therapeutic strategies to treat Candida infections. </jats:p> </jats:sec>

Metal-free organic polymer for the preparation of a reusable antimicrobial material with real-life application as an absorbent food pad

“…3, the fluorescence enhancement observed in the bacterial cells in contact with antimicrobial polymeric film APF1 demonstrates that the cell membrane integrity is compromised. These results agree with previous studies in which the antimicrobial effect of vanillin was produced by destabilization of cell membrane integrity, resulting in a loss of pH homeostasis and ionic balance (Fitzgerald et al, 2004;Saibabu et al, 2020). Therefore, the covalent immobilization of vanillin does not alter the mode of action of this essential oil.…”

Activity of Binary Combinations of Natural Phenolics and Synthetic Food Preservatives against Food Spoilage Yeasts

“…It has been reported that vanillin could interact synergistically with membrane targeting antifungals, leading to inhibition of fungal drug efflux pumps [ 35 ]. In another study, vanillin led to the disruption of fungal cell surface integrity, dysfunctional mitochondria, and DNA damage when used as a single agent [ 36 ]. Cinnamic acid has been proposed as a possible fungal growth inhibitor by interacting with benzoate 4-hydroxylase, crucial for aromatic detoxification [ 37 ].…”