tRNA修饰在维持生命所有领域的翻译准确性中起着重要作用。tRNA修饰机制的中断,尤其是反密码子茎环,可以致命的许多细菌,并导致广泛的表型面包师的酵母。关于tRNA修饰在宿主-病原体相互作用中的功能知之甚少,快速变化的环境和压力需要快速适应。我们发现两种密切相关的人类真菌病原体,高致病性白色念珠菌及其致病性低的姐妹物种,都柏林念珠菌,tRNA修饰酶的功能不同。这种酶,Hma1对两种真菌在菌丝形态中生长的能力表现出物种特异性影响,这是它们毒力潜力的核心。我们显示Hma1具有tRNA-苏酰基氨基甲酰基腺苷脱水酶活性,它的缺失改变了核糖体的占用,尤其是在37°C-人体宿主的体温下。白色念珠菌HMA1缺失突变体还显示出粘附和侵入人上皮细胞的缺陷,并在真菌感染模型中显示出降低的毒力。这将tRNA修饰与人类最重要的真菌病原体之一的宿主诱导的成丝和毒力联系起来。重要真菌感染在世界范围内呈上升趋势,它们对人类生命和健康的全球负担经常被低估。其中,人类共生和机会病原体,白色念珠菌,是严重感染的主要病原体之一。其毒力与其改变酵母至菌丝形态的能力密切相关。这里,这种能力首次与我们的知识有关,与tRNA的修饰和翻译效率有关。一种tRNA修饰酶,Hma1在白色念珠菌及其入侵宿主的能力中起着特定的作用。这为真菌毒力计划增加了迄今为止未知的调节层,并提供了新的潜在治疗靶标来对抗真菌感染。
tRNA modifications play important roles in maintaining translation accuracy in all domains of life. Disruptions in the tRNA modification machinery, especially of the anticodon stem loop, can be lethal for many bacteria and lead to a broad range of phenotypes in baker\'s yeast. Very little is known about the function of tRNA modifications in host-pathogen interactions, where rapidly changing environments and stresses require fast adaptations. We found that two closely related fungal pathogens of humans, the highly pathogenic Candida albicans and its much less pathogenic sister species, Candida dubliniensis, differ in the function of a tRNA-modifying enzyme. This enzyme, Hma1, exhibits species-specific effects on the ability of the two fungi to grow in the hypha morphology, which is central to their virulence potential. We show that Hma1 has tRNA-threonylcarbamoyladenosine dehydratase activity, and its deletion alters ribosome occupancy, especially at 37°C-the body temperature of the human host. A C. albicans HMA1 deletion mutant also shows defects in adhesion to and invasion into human epithelial cells and shows reduced virulence in a fungal infection model. This links tRNA modifications to host-induced filamentation and virulence of one of the most important fungal pathogens of humans.IMPORTANCEFungal infections are on the rise worldwide, and their global burden on human life and health is frequently underestimated. Among them, the human commensal and opportunistic pathogen, Candida albicans, is one of the major causative agents of severe infections. Its virulence is closely linked to its ability to change morphologies from yeasts to hyphae. Here, this ability is linked-to our knowledge for the first time-to modifications of tRNA and translational efficiency. One tRNA-modifying enzyme, Hma1, plays a specific role in C. albicans and its ability to invade the host. This adds a so-far unknown layer of regulation to the fungal virulence program and offers new potential therapeutic targets to fight fungal infections.