Abstract
Candida species causes superficial and life-threatening systemic infections and are difficult to treat due to the resistance of these organism to various clinically used drugs. Protolichesterinic acid is a well-known lichen compound. Although the antibacterial activity of protolichesterinic acid has been reported earlier, the antifungal property and its mechanism of action are still largely unidentified. The goal of the present investigation is to explore the anticandidal activity and mechanism of action of protolichesterinic acid, especially against Candida tropicalis. The Minimum Inhibitory Concentration (MIC) value was established through microdilution techniques against four Candida species and out of four species tested, C. tropicalis showed a significant effect (MIC: 2 μg/ml). In the morphological interference assay, we observed the enhanced inhibition of hyphae when the cells were treated with protolichesterinic acid. Time-kill assay demonstrated that the maximum rate of killing was recorded between 2 and 6 h. C. tropicalis exposed to protolichesterinic acid exhibited an increased ROS production, which is one of the key factors of fungal death. The rise in ROS was due to the dysfunction of mitochondria caused by protolichesterinic acid. We confirmed that protolichesterinic acid-induced dysfunction of mitochondria in C. tropicalis. The damage of cell membrane due to protolichesterinic acid treatment was confirmed by the influx of propidium iodide and was further confirmed by the release of potassium ions. The treatment of protolichesterinic acid also triggered calcium ion signaling. Moreover, it commenced apoptosis which is clearly evidenced by Annexin V and propidium iodide staining. Interestingly protolichesterinic acid recorded excellent immunomodulatory property when tested against lymphocytes. Finally protolichesterinic acid showed low toxicity toward a normal human cell line Foreskin (FS) normal fibroblast. In in vivo test, protolichesterinic acid significantly enhanced the survival of C. tropicalis infected Caenorhabditis elegans. This investigation proposes that the protolichesterinic acid induces apoptosis in C. tropicalis via the enhanced accumulation of intracellular ROS and mitochondrial damage, which leads fungal cell death via apoptosis. Our work revealed a new key aspect of mechanisms of action of protolichesterinic acid in Candida species. This article is the first study on the antifungal and mechanism of action of protolichesterinic acid in Candida species.
Highlights
The occurrence of infections due to pathogenic fungi has been Candida spp. are normal commensal microbes of humans, gradually growing as assessed to occur in more than a billion commonly found in the oral, gastrointestinal, urinary, and humans every year worldwide (Lee and Lee, 2014)
Previous studies conducted by various researchers on protolichesterinic acid have mainly focused on studying the preliminary antimicrobial property, there is a shortage of information on the antifungal effects especially against Candida species of this compound in literature
The foremost emphasis of the current investigation was to elucidate the growth was analyzed on the basis of the ability of living FS cells antifungal activity and preliminary mechanism of action of to reduce the yellow color of MTT dye (Sigma–Aldrich) to the protolichesterinic acid in Candida
Summary
The occurrence of infections due to pathogenic fungi has been Candida spp. are normal commensal microbes of humans, gradually growing as assessed to occur in more than a billion commonly found in the oral, gastrointestinal, urinary, and humans every year worldwide (Lee and Lee, 2014). Diseases vaginal mucosa (Alves et al, 2014), and produces superficial caused by pathogenic Candida spp. and other fungi continue and severe systemic infections. The Candida species represent second most numerous most commonly recovered from hospital fungal infections and agents causing fungal infection worldwide (Brown et al, 2012). Some Candida spp. is highly resistant to various clinically used azoles and polyenes drugs. E fungal infections in humans are caused by the Candida species viz. Candida albicans, Candida tropicalis, Candida glabrata, and Candida parapsilosis (Hwang et al, 2014). C compounds are used to treat various the fungal infections and this includes azoles, polyenes, fluoropyrimidines, echinocandins, and allylamines (Bhattacharya et al, 2015).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
