João Maria Eduarda Deluca, Tavanti Andrea Gomes, Vargas Alexandre Nascimento de, Kmetzsch Livia, Staats Charley Christian
Universidade Federal do Rio Grande do Sul (UFRGS), Centro de Biotecnologia, Programa de Pós-Graduação em Biologia Celular e Molecular, Porto Alegre, RS, Brazil.
Universidade Federal do Rio Grande do Sul (UFRGS), Instituto de Biociências, Departamento de Biologia Molecular e Biotecnologia, Porto Alegre, RS, Brazil.
Genet Mol Biol. 2024 Jul 29;47(2):e20230320. doi: 10.1590/1678-4685-GMB-2023-0320. eCollection 2024.
Free-living amoebas are natural predators of fungi, including human pathogens of the Cryptococcus genus. To survive and proliferate inside phagocytes, cryptococcal cells must acquire several nutrients. Zinc is fundamental for all life forms and develops a crucial role in the virulence of fungal pathogens, phagocytes reduce the availability of this metal to reduce the development of infection. The Acanthamoeba castellanii ACA1_271600 gene codes a metal transporter that is possibly associated with such antifungal strategy. Here, we evaluated the impact of A. castellanii metal homeostasis on C. gattii survival. Gene silencing of ACA1_271600 was performed and the interaction outcome of amoeba cells with both WT and zinc homeostasis-impaired mutant cryptococcal cells was evaluated. Decreased levels of ACA1_271600 in silenced amoeba cells led to higher proliferation of such cryptococcal strains. This effect was more pronounced in the zip1 mutant of C. gattii, suggesting that ACA1_271600 gene product modulates metal availability in Cryptococcus-infected amoebae. In addition, a systems biology analysis allowed us to infer that ACA1_271600 may also be involved in other biological processes that could compromise amoebae activity over cryptococcal cells. These results support the hypothesis that A. castellanii can apply nutritional immunity to hamper cryptococcal survival.
自由生活的变形虫是真菌的天然捕食者，包括隐球菌属的人类病原体。为了在吞噬细胞内生存和增殖，隐球菌细胞必须获取多种营养物质。锌对所有生命形式都至关重要，并且在真菌病原体的毒力中发挥关键作用，吞噬细胞会降低这种金属的可用性以减少感染的发展。卡氏棘阿米巴的ACA1_271600基因编码一种金属转运蛋白，可能与这种抗真菌策略有关。在这里，我们评估了卡氏棘阿米巴金属稳态对加氏隐球菌生存的影响。我们对ACA1_271600进行了基因沉默，并评估了变形虫细胞与野生型和锌稳态受损的突变隐球菌细胞的相互作用结果。沉默的变形虫细胞中ACA1_271600水平降低导致此类隐球菌菌株的增殖增加。这种效应在加氏隐球菌的zip1突变体中更为明显，这表明ACA1_271600基因产物调节隐球菌感染的变形虫中的金属可用性。此外，系统生物学分析使我们推断ACA1_271600也可能参与其他可能损害变形虫对隐球菌细胞活性的生物学过程。这些结果支持了卡氏棘阿米巴可以应用营养免疫来阻碍隐球菌生存的假设。
