Carvajal Silvia Katherine, Vargas-Casanova Yerly, Pineda-Castañeda Héctor Manuel, García-Castañeda Javier Eduardo, Rivera-Monroy Zuly Jenny, Parra-Giraldo Claudia Marcela
Unidad de Proteómica y Micosis Humanas, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C. 110231, Colombia.
Chemistry Department, Universidad Nacional de Colombia, Carrera 45 No. 26-85, Building 451, Office 409, Bogotá D.C. 111321, Colombia.
Antibiotics (Basel). 2022 Dec 15;11(12):1819. doi: 10.3390/antibiotics11121819.
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 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 var. 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.
隐球菌病与高发病率和死亡率相关。抗真菌药物数量有限、具有毒性,且这些分子难以穿过血脑屏障,这使得探索针对隐球菌病的新治疗候选药物成为一项优先任务。为了优化抗菌功能并改善抗菌肽的物理化学性质,化学策略包括将肽片段组合成一个。本研究旨在评估牛乳铁蛋白素(LfcinB)和蟾蜍 Buforin II(BFII)的最小活性基序对新型隐球菌变种的结合情况。针对这些嵌合体的抗真菌活性进行了评估,对象包括:(i)参考菌株 H99,(ii)三株哥伦比亚临床菌株,以及(iii)十一株突变菌株,目的是评估可能的抗真菌靶点。我们发现这些嵌合体对这些菌株具有高活性,最低抑菌浓度(MIC)在 6.25 至 12.5 µg/mL 之间。开展了研究以评估氟康唑联合治疗的效果,发现了协同效应。最后,当用 12.5 µg/mL 的嵌合体处理成纤维细胞时,发现细胞活力超过 65%。本研究获得的结果表明,这些嵌合体是未来用于治疗隐球菌病的潜在抗真菌分子。