Candida spp. are common opportunistic microorganisms in the human body and can cause mucosal, cutaneous, and systemic infections, mainly in individuals with weakened immune systems. Candida albicans is the most isolated and pathogenic species; however, multi-drug-resistant yeasts like Candida auris have recently been found in many different regions of the world. The increasing development of resistance to common antifungals by Candida species limits the therapeutic options. In light of this, the present review attempts to discuss the significance of marine natural products in controlling the proliferation and metabolism of C. albicans and non-albicans species. Natural compounds produced by sponges, algae, sea cucumber, bacteria, fungi, and other marine organisms have been the subject of numerous studies since the 1980s, with the discovery of several products with different chemical frameworks that can inhibit Candida spp., including antifungal drug-resistant strains. Sponges fall under the topmost category when compared to all other organisms investigated. Terpenoids, sterols, and alkaloids from this group exhibit a wide array of inhibitory activity against different Candida species. Especially, hippolide J, a pair of enantiomeric sesterterpenoids isolated from the marine sponge Hippospongia lachne, exhibited strong activity against Candida albicans, Candida parapsilosis, and Candida glabrata. In addition, a comprehensive analysis was performed to unveil the mechanisms of action and synergistic activity of marine products with conventional antifungals. In general, the results of this review show that the majority of chemicals derived from the marine environment are able to control particular functions of microorganisms belonging to the Candida genus, which can provide insights into designing new anti-candidal therapies.

Candida albicans catheter-related candidemia is largely driven by microbial adhesion and biofilm formation on central venous catheters. Cells that disperse from these biofilms can enter the bloodstream, spread to distant organs, and sustain the cycle of infection. In this study, we investigated the virulence potential of C. albicans isolates obtained from the blood of catheterized patients experiencing persistent candidemia, comparing them to isolates that were cleared from the bloodstream early in the infection. Our results show that isolates persisting in the bloodstream for 4 days or longer, despite antifungal treatment, exhibited enhanced adherence, filamentation, and biofilm formation in vitro, along with increased expression of key virulence-related genes. Notably, cells dispersed from second-generation biofilms formed by these persistent isolates displayed even more pronounced pathogenic characteristics, including improved immune evasion. Furthermore, in vivo experiments using Galleria mellonella revealed that persistent isolates were significantly more virulent than their nonpersistent counterparts.

Natural compound-based strategies have gained attention as alternatives to conventional antifungal therapies, particularly in the management of Candida infections affecting the oral cavity, such as denture stomatitis. Our aim was to investigate the antifungal activity of the polyphenol pterostilbene (PTE) on clinical Candida isolates and microcosm biofilms from denture stomatitis, as well as to evaluate its toxicity and therapeutic efficacy in Galleria mellonella. PTE exhibited fungicidal effects against Candida albicans and Candida dubliniensis at 32 µg/mL. Time-kill assays demonstrated complete inhibition of viability for both strains within 8 h of exposure. In addition, PTE exhibited broad-spectrum antimicrobial activity, significantly reducing the counts of streptococci, mutans streptococci, staphylococci, and yeasts within microcosm biofilms. In vivo, PTE showed no signs of toxicity in G. mellonella at concentrations up to 20× MIC. Prophylactic treatment with PTE enhanced larval survival in experimental candidiasis caused by both C. albicans and C. dubliniensis. Moreover, prophylactic treatment decreased the fungal burden of C. albicans in the G. mellonella hemolymph, while the recruitment of hemocytes involved in host defense mechanisms remained unaltered. In summary, PTE demonstrated antimicrobial activity against Candida planktonic cells and complex biofilms associated with denture stomatitis, exhibiting favorable biocompatibility and in vivo antifungal efficacy in G. mellonella model.