Andrade-Pavón Dulce, Gómez-García Omar
Laboratorio de Biología Molecular de Bacterias Y Levaduras, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio Y Plan de Ayala. Col. Sto. Tomás, 11340 México City, México.
Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu S/N Unidad Profesional "Adolfo López Mateos", Zacatenco. Col. Lindavista, Del, 07700 Venustiano Carranza, D.F México.
Indian J Microbiol. 2021 Sep;61(3):306-314. doi: 10.1007/s12088-021-00942-6. Epub 2021 May 5.
Candidemia, one of the most common invasive fungal infections in hospitalized patients, can lead to death and huge financial losses. is the main causative agent of this disorder and occupies the second or third place, for which new therapeutic alternatives must be found. The objective of the present study was to evaluate the inhibitory effect of etoposide and camptothecin (inhibitors of deoxyribonucleic acid (DNA) topoisomerase) on the CBS138 strain. Etoposide and camptothecin showed better or similar MIC (minimum inhibitory concentration) (5 and 2.5 μg/mL, respectively), with respect to fluconazole (8 μg/mL) and itraconazole (4 μg/mL). They also suppressed colony formation during the 12-h test. On the other hand, colonies were less formed by exposing to etoposide or camptothecin (indicating low toxicity), with respect fluconazole and itraconazole. Such colonies are phenotypically observed as limited growth in medium containing a non-fermentable carbon source, and are genotypically characterized by a partial or total loss of mitochondrial DNA (mtDNA) fragments. Using PCR techniques and cell staining with 4',6-diamidino-2-phenylindole (DAPI), loss of mtDNA was detected only in yeast cells treated with fluconazole. Additionally, molecular docking studies with etoposide and camptothecin showed recognition in the active site of the Topo I and II enzymes from . Since etoposide and camptothecin showed good inhibitory activity and low toxicity on ; they should certainly be of interest for the treatment of infections and the design and development of new antifungal compounds derived from these drugs.
The online version contains supplementary material available at 10.1007/s12088-021-00942-6.
念珠菌血症是住院患者中最常见的侵袭性真菌感染之一，可导致死亡和巨大的经济损失。白色念珠菌是这种疾病的主要病原体，热带念珠菌位居第二或第三，必须找到新的治疗方法。本研究的目的是评估依托泊苷和喜树碱（脱氧核糖核酸（DNA）拓扑异构酶抑制剂）对热带念珠菌CBS138菌株的抑制作用。依托泊苷和喜树碱的最低抑菌浓度（MIC）（分别为5和2.5μg/mL）优于或类似于氟康唑（8μg/mL）和伊曲康唑（4μg/mL）。在12小时的测试中，它们还抑制了菌落形成。另一方面，与氟康唑和伊曲康唑相比，暴露于依托泊苷或喜树碱的热带念珠菌形成的菌落较少（表明毒性较低）。这种菌落在含有不可发酵碳源的培养基中表现为有限生长，在基因上的特征是线粒体DNA（mtDNA）片段部分或全部丢失。使用PCR技术和4',6-二脒基-2-苯基吲哚（DAPI）细胞染色，仅在氟康唑处理的酵母细胞中检测到mtDNA的丢失。此外，依托泊苷和喜树碱的分子对接研究表明它们能识别热带念珠菌拓扑异构酶I和II的活性位点。由于依托泊苷和喜树碱对热带念珠菌显示出良好的抑制活性和低毒性，它们无疑将有助于治疗热带念珠菌感染以及设计和开发源自这些药物的新型抗真菌化合物。
在线版本包含可在10.1007/s12088-021-00942-6获取的补充材料。
