Antifungal Effect and Inhibition of the Virulence Mechanism of D-Limonene against Candida parapsilosis

Abstract

Yeasts from the Candida parapsilosis complex are clinically relevant due to their high virulence and pathogenicity potential, such as adherence to epithelial cells and emission of filamentous structures, as well as their low susceptibility to antifungals. D-limonene, a natural compound, emerges as a promising alternative with previously described antibacterial, antiparasitic, and antifungal activity; however, its mechanisms of action and antivirulence activity against C. parapsilosis complex species have not been elucidated. Therefore, in the present study, we aimed to evaluate the antifungal and antivirulence action, as well as the mechanism of action of D-limonene against isolates from this complex. D-limonene exhibited relevant antifungal activity against C. parapsilosis complex yeasts, as well as excellent antivirulence activity by inhibiting yeast morphogenesis and adherence to the human epithelium. Furthermore, the apoptotic mechanism induced by this compound, which is not induced by oxidative stress, represents an important target for the development of new antifungal drugs.

Transcriptional Reprogramming of Candida tropicalis in Response to Isoespintanol Treatment

“…Furthermore, the upregulation of the STI1 domain, known for its role in various cellular processes, including the transfer of hydrophobic substrates and the DNA damage response, suggests that ISO's antifungal action also involves DNA damage in C. tropicalis. Our results are in accordance with previous studies in C. tropicalis and C. parapsilosis, where terpenes like D-limonene have exhibited multiple action targets [24,25,103].…”

“…Regrettably, the three principal antifungal drug classes (polyenes, echinocandins, and azoles) have been unable to stem the surge in life-threatening fungal infections observed over the past few decades [22]. In response to this pressing clinical challenge, compounds derived from botanical sources have gained traction as a promising alternative [23][24][25]. In our previous investigations, we established that isoespintanol (ISO), a monoterpene derived from Oxandra xylopioides, exhibits potent antifungal properties against Candida tropicalis [26,27].…”

Chemical Profile, Anti-Microbial and Anti-Inflammaging Activities of Santolina rosmarinifolia L. Essential Oil from Portugal

“…and A. fumigatus [59][60][61][62][63]. Several studies reported the antifungal effect of limonene against Candida spp., A. fumigatus, T. rubrum and several other fungi [60,[64][65][66][67][68][69][70]. In contrast, borneol presented a very weak activity against several fungal strains [60,[71][72][73][74].…”

D-Limonene: Promising and Sustainable Natural Bioactive Compound

“…And for fungi, it was shown that D-limonene induced disruption of the specific cell differentiation program of C. parapsilosis, leading to apoptosis, and also arrested the cell cycle of C. albicans in the G1 phase and the abundancies of 52 proteins were significantly changed (≥two-fold), 33 of which were upregulated and 19 downregulated. Furthermore, qPCR demonstrated that C. albicans cell wall and cell membrane damage stress genes (KRE 9, ERG 11), oxidative stress genes (TRR 1), nucleolus stress genes (PRL 11), and apoptosis-related genes (CaMCA 1) were overexpressed, indicating that D-limonene can induce apoptosis in C. albicans cells through multiple pathways [85,93].…”