Candida auris, first described in 2009, is an opportunistic pathogenic yeast that causes nosocomial outbreaks around the world, with high mortality rates associated with therapeutic failure. In this study, we evaluated the pathogenicity of 107 isolates from two cities in Colombia, associated with fungemia or colonization processes; to achieve this, we used the Galleria mellonella invertebrate model to compare pathogenicity. Our results showed that less than half of the total isolates of C. auris presented a high pathogenicity compared to the reference strain SC5314, and most of those highly pathogenic strains were from colonization processes. We observed that there was formation of large aggregates of cells that cannot be disrupted easily, without statistically significant differences between the pathogenicity of the aggregated and non-aggregated strains. In addition, protease activity was observed in 100% of the C. auris strains; phospholipase and hemolysin activity were observed in 67.3 and 68.2% of the studied strains, respectively. In conclusion, these results highlight the utility of determining survival using G. mellonella, which allowed us to provide new information on the pathogenicity, enzymatic activity, and the relationship of the aggregated and non-aggregated phenotypes of C. auris in this model.

Cryptococcosis, a life-threatening mycosis caused mainly by Cryptococcus neoformans, appears to be distinctly rare in hematopoietic stem cell transplant (HSCT) recipients. When it occurs, this fungal infection is a major limitation for a successful transplant. This review comprehensively analyses 24 cases, reported in the literature, of patients with haematological malignancies including leukemias, multiple myeloma, and lymphomas, as indication for HSCT, who presented with cryptococcosis after transplantation. Of the 24 cases, 11 each occurred in patients receiving allogeneic and autologous stem cell transplants, from bone marrow, peripheral blood, and umbilical cord blood. HSCT recipients were slightly more often male, and the age of the patients ranged from 12 to 74 years. Antifungal prophylaxis was reported in most cases. Clinical manifestations of cryptococcal disease included more frequently central nervous system involvement followed by fungaemia, disseminated infection, pulmonary cryptococcosis, cerebellitis, and diarrhea. Diagnosis differed depending on the clinical presentation but habitually included cryptococcal antigen assay, India ink, and culture. Notably, not only C. neoformans but also C. albidus, C. terreus, C. laurentii, and C. adeliensis were identified as the causal species, the last two including strains resistant to fluconazole. Amphotericin B, alone or in combination, was the most common antifungal drug used for the treatment of cryptococcosis in HSCT recipients. Due to the small number of cases, it was not possible to establish if mortality rate, which was the same as survival rate, depends on the effect of the immunosuppressive regimen, the site of cryptococcal infection, and/or the antifungal therapy used to control the mycosis. Although uncommon, the recognition of cryptococcal disease in stem cell transplant is essential for a timely and adequate treatment, improved prognosis, reduced morbidity and mortality, and successful transplantation.

Cryptococcosis is associated with high rates of morbidity and mortality. The limited number of antifungal agents, their toxicity, and the difficulty of these molecules in crossing the blood–brain barrier have made the exploration of new therapeutic candidates against Cryptococcus neoformans a priority task. To optimize the antimicrobial functionality and improve the physicochemical properties of AMPs, chemical strategies include combinations of peptide fragments into one. This study aimed to evaluate the binding of the minimum activity motif of bovine lactoferricin (LfcinB) and buforin II (BFII) against C. neoformans var. grubii. The antifungal activity against these chimeras was evaluated against (i) the reference strain H99, (ii) three Colombian clinical strains, and (iii) eleven mutant strains, with the aim of evaluating the possible antifungal target. We found high activity against these strains, with a MIC between 6.25 and 12.5 µg/mL. Studies were carried out to evaluate the effect of the combination of fluconazole treatments, finding a synergistic effect. Finally, when fibroblast cells were treated with 12.5 µg/mL of the chimeras, a viability of more than 65% was found. The results obtained in this study identify these chimeras as potential antifungal molecules for future therapeutic applications against cryptococcosis.

This study reports the synthesis, characterization, and antifungal evaluation of a series of pyridoxal and salicylaldehyde derivatives, using synthetic methodologies such as radical cyclizations and click chemistry. Compounds 6a and 6b, featuring a fused dihydrobenzoxepine-pyridine scaffold, demonstrated effective fungicidal activity with MIC values of 19 µg/mL against Cryptococcus neoformans 2807. Similarly, compound 6b exhibited notable activity with a MIC of 75 µg/mL against Candida auris PUJ-HUSI 537. Both compounds outperformed fluconazole (FLC) in these strains. In silico ADMET profiling revealed favorable pharmacokinetic properties, including blood–brain barrier penetration and drug-likeness parameters consistent with Lipinski’s rule of five. Cytotoxicity assays on human fibroblasts confirmed the low toxicity of compound 6a at the tested concentrations. These results highlight the potential of the fused dihydrobenzoxepine-pyridine scaffold as a promising antifungal candidate for further investigations.