The secreted aspartic peptidases (Saps) of Candida albicans play crucial roles in various steps of fungal–host interactions. Using a flow cytometry approach, this study investigated the expression of Saps1–3 antigens after (i) incubation with soluble proteins, (ii) interaction with mammalian cells, and (iii) infection in immunosuppressed BALB/c mice. Supplementation strategies involving increasing concentrations of bovine serum albumin (BSA) added to yeast carbon base (YCB) medium as the sole nitrogenous source revealed a positive and significant correlation between BSA concentration and both the growth rate and the percentage of fluorescent cells (%FC) labeled with anti-Saps1–3 antibodies. Supplementing the YCB medium with various soluble proteins significantly modulated the expression of Saps1–3 antigens in C. albicans. Specifically, immunoglobulin G, gelatin, and total bovine/human sera significantly reduced the %FC, while laminin, human serum albumin, fibrinogen, hemoglobin, and mucin considerably increased the %FC compared to BSA. Furthermore, co-cultivating C. albicans yeasts with either live epithelial or macrophage cells induced the expression of Saps1–3 antigens in 78% (mean fluorescence intensity [MFI] = 152.1) and 82.7% (MFI = 178.2) of the yeast cells, respectively, compared to BSA, which resulted in 29.3% fluorescent cells (MFI = 50.9). Lastly, the yeasts recovered from the kidneys of infected immunosuppressed mice demonstrated a 4.8-fold increase in the production of Saps1–3 antigens (MFI = 246.6) compared to BSA, with 95.5% of yeasts labeled with anti-Saps1–3 antibodies. Altogether, these results demonstrated the positive modulation of Saps’ expression in C. albicans by various key host proteinaceous components, as well as by in vitro and in vivo host challenges.

Candida species commonly secrete aspartic peptidases (Saps), which are virulence factors involved in nutrient acquisition, colonization, tissue invasion, immune evasion and host adaptation. However, the regulation of Sap production remains poorly characterized in emerging, widespread and multidrug-resistant members of the Candida haemulonii clade (C. auris, C. haemulonii, C. haemulonii var. vulnera and C. duobushaemulonii). This study investigated the influence of temperature, pH and protein substrate on Sap production using bloodstream isolates of the C. haemulonii clade. Sap activity was initially assessed using the enzyme coefficient (Pz) in fungal cells grown on yeast carbon base (YCB) agar supplemented with bovine serum albumin (BSA) to determine optimal conditions for enzymatic production. C. auris and C. duobushaemulonii exhibited the highest Sap activity at 96 h, pH 4.0–5.0, and 37 °C, whereas C. haemulonii and C. haemulonii var. vulnera displayed more variable and isolate-dependent profiles. Sap production was markedly suppressed at pH 6.0. The addition of pepstatin A, an inhibitor of aspartic peptidases, abolished Sap activity and impaired fungal growth in a dose-dependent manner, confirming both the enzymatic identity and its critical role in nitrogen acquisition. Conversely, YCB supplemented with an inorganic nitrogen source (ammonium sulfate) supported fungal growth but did not induce Sap production. To explore substrate specificity, YCB was supplemented with a panel of proteins. Serum albumins (bovine and human) induced the highest Sap production, followed by globulin, gelatin, hemoglobin, collagen and immunoglobulin G, while elastin and mucin elicited the lowest Sap production. Isolate-specific preferences for protein substrates were observed. Finally, fluorometric assays using a Sap-specific fluorogenic peptide substrate confirmed the presence of Sap activity in cell-free supernatants, which was consistently and entirely blocked by pepstatin A. These findings highlight inter- and intraspecies variability in Sap regulation among C. haemulonii clade, stressing the critical roles of substrate availability, pH and temperature in shaping fungal adaptation to host environments.

Fungi are tiny organisms found everywhere—in nature, in our homes, and even in and on our bodies. Similar to how people cooperate in cities, fungi can form cooperative communities known as fungal biofilms. Biofilms consist of clusters of fungal cells sticking together, and they can often survive on surfaces for long periods, making them difficult to eliminate. Fungal biofilms are especially dangerous in healthcare settings, because they can grow on surfaces and medical devices. Scientists are actively investigating ways to tackle this issue, such as using combining medicines or using drugs in new ways. In this article, we will talk about how fungal biofilms form, how they can cause problems in hospitals, and how they can be managed. Understanding and addressing these challenges are essential for keeping patients safe from fungal infections.

1,10-Phenanthroline-5,6-dione (phendione) is a functionalized derivative of 1,10-phenanthroline bearing two carbonyl groups at the 5,6-positions, which enhance its electron-accepting ability, polarity and coordination versatility. These structural features enable phendione to act as a bidentate ligand for a variety of transition metals, forming stable coordination compounds (or complexes) widely explored in coordination chemistry, catalysis, materials science and redox systems. In addition, phendione and its metal complexes have demonstrated relevant biological activities, including antibacterial, antifungal and antiprotozoal effects, attributed to DNA interaction, redox cycling, inhibition of key enzymes and interference with essential microbial processes such as protein synthesis. In the context of the escalating global burden of antimicrobial resistance, the discovery and development of innovative therapeutic strategies have become an urgent priority. In this scenario, phendione-based complexes have emerged as promising candidates owing to their remarkable structural diversity, versatile coordination chemistry, tunable physicochemical properties and ability to engage multiple and distinct mechanisms of action that differ from those of currently available clinical antimicrobial drugs. These characteristics provide opportunities for overcoming existing therapeutic limitations and expanding the arsenal of antimicrobial agents, particularly against clinically relevant pathogenic microorganisms, including multidrug- and pan-resistant strains for which effective treatment options remain critically limited. The present review provides a comprehensive and critical analysis of the current literature concerning the synthesis, structural features and antimicrobial properties of phendione-containing complexes, highlighting their potential as promising next-generation antimicrobial agents and exploring their mechanisms of action, biological relevance and future perspectives in the development of innovative therapies.