Multi-drug resistance is becoming an increasingly severe clinical challenge not only among pathogenic bacteria but among fungal pathogens as well. Drug design is inherently more challenging for the eukaryotic fungi due to their closer evolutionary similarity to humans. The recent rapid expansion in invasive infections throughout the world by Candida auris is of particular concern due to a substantial mortality rate, comparatively facile transmission, and an increasing level of resistance to all three of the major classes of anti-fungal drugs. One promising avenue for the development of an alternative class of anti-fungal agents currently under investigation is for drugs against the FK506-binding protein FKBP12 which, when bound to that drug, inhibits the fungal calcineurin signaling pathway with a resultant diminution in virulence. The specific challenge to this approach is that the homologous human calcineurin pathway functions in controlling the tissue immunity response, so that drug selectivity for the fungal pathway must be designed. To facilitate such efforts, we report the nearly complete backbone and sidechain resonances for the FKBP12 proteins of both Candida auris and clinically significant Candida glabrata fungi.

中文翻译：

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来自病原性真菌假丝酵母和光滑假丝酵母的FKBP12蛋白的1H，13C，15 N化学位移分配。

不仅在致病细菌中而且在真菌病原体中，多药耐药性也正成为日益严峻的临床挑战。由于其与人类的进化相似性，对于真核真菌而言，药物设计固有地更具挑战性。最近念珠菌侵袭性感染在世界范围内迅速扩展由于死亡率高，传播相对容易并且对所有三种主要的抗真菌药物的耐药性不断提高，这一点尤其令人关注。目前正在研究开发另一类抗真菌剂的有前途的途径是针对FK506结合蛋白FKBP12的药物，该药物与FKBP12结合后会抑制真菌钙调神经磷酸酶的信号传导途径，从而降低毒力。这种方法的特殊挑战是同源的人钙调磷酸酶途径在控制组织免疫应答中起作用，因此必须设计对真菌途径的药物选择性。为了促进此类工作，我们报告了两个假丝酵母的FKBP12蛋白几乎完整的骨架和侧链共振和具有临床意义的光滑念珠菌。