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 auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and immunocompromised individuals. The development of drug resistance is the major factor associated with the therapeutic failure of existing antifungal agents. Previous studies have addressed the antifungal resistance profile and drug discovery for C. auris. However, complete coverage of this information in a single investigation is not yet available. In this review, we have mainly focused on recent developments in therapeutic strategies against C. auris. Based on the available information, several different approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, synthetic chemicals, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Therefore, we anticipate that the findings gathered in this review will encourage further in vivo studies and clinical trials.

Cryptococcal infection commonly begins as an opportunistic infection in humans, however, this can escalate to a systemic or life-threatening form in immunocompromised individuals. Here, we aim to identify novel antifungal molecules from plants resources. Sclareolide, a phytochemical classified as a sesquiterpene lactone, was assessed against Cryptococcus neoformans H99. Sclareolide exhibited promising antifungal properties with a minimum inhibitory concentration (MIC) of 16 µg/mL. Additionally, the C. neoformans growth rate was significantly affected by sclareolide treatment in a concentration-dependent manner, as observed through a time killing assay, with a significant reduction at MIC × 8 compared to the control by 48 h. To elucidate the underlying mechanisms of sclareolide antifungal activity, fluorescence-based methods were employed. Propidium iodide (PI) accumulation assay indicated a reduction in C. neoformans membrane integrity, with values as low as 6.62 ± 0.18% after treatment. Moreover, sclareolide at MIC × 4 and MIC × 8 significantly increased the production of reactive oxygen species (ROS) and reduced the mitochondrial membrane potential (MMP), suggesting oxidative stress and mitochondrial dysfunction in C. neoformans. Sclareolide did not induce caspase-dependent apoptosis, suggesting a non-apoptotic mechanism. Further, a checkerboard experiment was performed to assess potential synergistic interaction with Amphotericin B, however, no synergism was observed. Moving on, sclareolide at 128 µg/mL did not exhibit toxicity in Galleria mellonella, further supporting its potential as a safe antifungal agent. These findings suggest that the antifungal activity of sclareolide against C. neoformans is mediated by oxidative stress. Further in vivo and pharmacokinetic studies are recommended to explore the potential of sclareolide as a prototype for the development of novel anti-cryptococcal therapies.

Candidiasis is a common infection primarily caused by the opportunistic fungus Candida albicans . Conventional antifungals have been associated with several limitations, and today, antimicrobial photodynamic therapy (aPDT) is raised as an adjuvant treatment. This study aimed to develop a carrier system for the photosensitizer methylene blue (MB) based on a gellan gum (GG) hydrogel, a nontoxic exopolysaccharide. Two formulations consisting of 0.6% and 1.0% (w/v) GG containing MB were prepared and characterized in relation to release kinetics, absorption spectroscopy, and optical shield formation. Then, the effects of MB GG formulations in aPDT using LED irradiation were evaluated against C. albicans. For this, aPDT was applied toC. albicans in planktonic and biofilm stages and also tested in a Galleria mellonella burn infection model. The successful incorporation of MB into the GG hydrogel was confirmed by absorption spectroscopy, with a characteristic peak at 660 nm for intact MB and both GG formulations. The GG0.6% hydrogel released 100% of MB in 12 min, whereas the GG1.0% hydrogel released only 75% of MB after 25 min. Furthermore, no optical shield formation was noticed with the MB gellan formulations in comparison to the aqueous form. In relation to antifungal activity on C. albicans, aPDT with GG0.6% and GG1.0% containing MB led to an eradication of planktonic cells and a partial reduction of biofilms, as observed in aPDT with MB aqueous. When aPDT was applied in G. mellonella larvae, an increase of 50% and 30% in survival rate was found, respectively, for the groups treated with MB gellan formulation and MB aqueous. In conclusion, the gellan gum formulations designed here were able to release MB and maintain its optical and photodynamic properties against C. albicans. In addition, aPDT with MB gellan formulations had higher in vivo efficacy than MB aqueous.