Zamith-Miranda Daniel, Amatuzzi Rafaela F, Munhoz da Rocha Isadora F, Martins Sharon T, Lucena Aline C R, Vieira Alexandre Z, Trentin Gabriel, Almeida Fausto, Rodrigues Marcio L, Nakayasu Ernesto S, Nosanchuk Joshua D, Alves Lysangela R
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Comput Struct Biotechnol J. 2021 Sep 14;19:5264-5277. doi: 10.1016/j.csbj.2021.09.007. eCollection 2021.
has emerged as a serious worldwide threat by causing opportunistic infections that are frequently resistant to one or more conventional antifungal medications resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understanding fungal biology and effective prevention and treatment approaches to combat this fungus. To date, there is little information about the differentially expressed genes when this fungus is treated with conventional antifungals, and caspofungin is a standard echinocandin deployed in the therapy against . In this work, we treated two distinct strains of for 24 h with caspofungin, and the cellular responses were evaluated at the morphological, translational and transcriptional levels. We first observed that the echinocandin caused morphological alterations, aggregation of yeast cells, and modifications in the cell wall composition of . Transcriptomic analysis revealed an upregulation of genes related to the synthesis of the cell wall, ribosome, and cell cycle after exposure to caspofungin. Supporting these findings, the integrated proteomic analysis showed that caspofungin-treated cells were enriched in ribosome-related proteins and cell wall, especially mannoproteins. Altogether, these results provide further insights into the biology of and expands our understanding regarding the antifungal activity of caspofungin and reveal cellular targets, as the mannose metabolism, that can be further explored for the development of novel antifungals.
通过引起机会性感染已成为一种严重的全球威胁，这些感染通常对一种或多种传统抗真菌药物耐药，导致高死亡率。在此背景下，世界各地的健康警告都集中在了解真菌生物学以及对抗这种真菌的有效预防和治疗方法上。迄今为止，关于用传统抗真菌药物治疗这种真菌时差异表达基因的信息很少，而卡泊芬净是用于治疗……的标准棘白菌素。在这项工作中，我们用卡泊芬净处理了两种不同的……菌株24小时，并在形态、翻译和转录水平评估了细胞反应。我们首先观察到棘白菌素引起了形态改变、酵母细胞聚集以及……细胞壁组成的改变。转录组分析显示，暴露于卡泊芬净后，与细胞壁合成、核糖体和细胞周期相关的基因上调。支持这些发现的是，综合蛋白质组分析表明，用卡泊芬净处理的细胞富含核糖体相关蛋白和细胞壁，尤其是甘露糖蛋白。总之，这些结果为……的生物学提供了进一步的见解，扩展了我们对卡泊芬净抗真菌活性的理解，并揭示了可作为甘露糖代谢的细胞靶点，可进一步探索用于开发新型抗真菌药物。
