Shevchenko Olga V, Voropaev Alexander D, Bogdanov Ivan V, Ovchinnikova Tatiana V, Finkina Ekaterina I
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Moscow Center for Advanced Studies, 123592 Moscow, Russia.
Pathogens. 2024 Dec 10;13(12):1092. doi: 10.3390/pathogens13121092.
Today, is still the most common cause of both local and life-threatening systemic candidiasis. The spread of resistant fungal strains has resulted in an urgent need to search for new promising antimycotics. Here, we investigated the antifungal action of the tobacco defensin NaD1 against susceptible and resistant to azoles and echinocandins strains of . We demonstrated that NaD1 was equally effective and fungicidal against all tested strains. The MIC and MFC values were 6.25 and 12.5 µM, respectively. We showed for the first time that NaD1 could act synergistically not only with caspofungin but also with human host defense antimicrobial peptides cathelicidin LL-37 and β-defensin-2 (HBD2) against susceptible and resistant fungal strains. Using flow cytometry, we demonstrated that NaD1 in combinations with LL-37 or HBD2 can reinforce each other by enhancing membrane disruption. Using the Caco-2 cell monolayer model, we demonstrated that NaD1 impaired the adhesion of cells to the human epithelium. Moreover, NaD1 inhibited the formation of fungal biofilms in Sabouraud broth and less markedly in nutrient-rich RPMI-1640 medium, and enhanced the antibiofilm activity of caspofungin. Thus, we hypothesized that NaD1 might affect the development of candidiasis in vivo, including that caused by resistant fungal strains.
如今，仍是局部和危及生命的全身性念珠菌病最常见的病因。耐药真菌菌株的传播导致迫切需要寻找新的有前景的抗真菌药物。在此，我们研究了烟草防御素NaD1对唑类和棘白菌素敏感及耐药菌株的抗真菌作用。我们证明NaD1对所有测试菌株均具有同等效力且具有杀菌作用。其MIC和MFC值分别为6.25和12.5 µM。我们首次表明，NaD1不仅能与卡泊芬净协同作用，还能与人类宿主防御抗菌肽cathelicidin LL-37和β-防御素-2（HBD2）协同作用，对抗敏感和耐药真菌菌株。通过流式细胞术，我们证明NaD1与LL-37或HBD2联合使用可通过增强膜破坏作用而相互增强。使用Caco-2细胞单层模型，我们证明NaD1可削弱细胞对人上皮细胞的黏附。此外，NaD1在沙氏肉汤中抑制真菌生物膜的形成，在营养丰富的RPMI-1640培养基中抑制作用较弱，并增强了卡泊芬净的抗生物膜活性。因此，我们推测NaD1可能会影响体内念珠菌病的发展，包括由耐药真菌菌株引起的念珠菌病。
