宿主-真菌病原体战场上的金属。
Metals at the Host-Fungal Pathogen Battleground.
机构信息
Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; email:
出版信息
Annu Rev Microbiol. 2024 Nov;78(1):23-38. doi: 10.1146/annurev-micro-041222-023745. Epub 2024 Nov 7.
Fungal infections continue to represent a major threat to public health, particularly with the emergence of multidrug-resistant fungal pathogens. As part of the innate immune response, the host modulates the availability of metals as armament against pathogenic microbes, including fungi. The transition metals Fe, Cu, Zn, and Mn are essential micronutrients for all life forms, but when present in excess, these same metals are potent toxins. The host exploits the double-edged sword of these metals, and will either withhold metal micronutrients from pathogenic fungi or attack them with toxic doses. In response to these attacks, fungal pathogens cleverly adapt by modulating metal transport, metal storage, and usage of metals as cofactors for enzymes. Here we review the current state of understanding on Fe, Cu, Zn, and Mn at the host-fungal pathogen battleground and provide perspectives for future research, including a hope for new antifungals based on metals.
真菌感染仍然是对公众健康的重大威胁,特别是随着多药耐药真菌病原体的出现。作为先天免疫反应的一部分,宿主调节金属的可用性,作为对抗包括真菌在内的病原微生物的武器。过渡金属铁、铜、锌和锰是所有生命形式的必需微量元素,但当过量存在时,这些相同的金属是强烈的毒素。宿主利用这些金属的双刃剑,要么从病原真菌中扣留金属微量元素,要么用有毒剂量攻击它们。真菌病原体对这些攻击做出了巧妙的适应,通过调节金属运输、金属储存以及将金属用作酶的辅助因子来实现。在这里,我们综述了宿主-真菌病原体战场中铁、铜、锌和锰的最新理解,并为未来的研究提供了展望,包括希望基于金属开发新的抗真菌药物。