Zhu Chenhua, Liu Qi, Chen Yuhan, Tian Fangfang, Kong Dekun, Happacher Isidor, Haas Hubertus, Zhang Yongjun, Luo Zhibing
Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Plant Protection, Southwest University, Chongqing, China.
College of Pharmaceutical Sciences, Southwest University, Chongqing, China.
mBio. 2025 Aug 25:e0198125. doi: 10.1128/mbio.01981-25.
Nutritional immunity plays a vital role in limiting the proliferation of microbial pathogens in vertebrates and invertebrates. During coevolution with their hosts, pathogens have developed tactics to counteract the host nutritional immunity by acquiring iron via iderophore-ron ransporter (SIT)-mediated uptake of siderophore-iron chelates. However, little is known about the role of SITs of insect fungal pathogens in combating host immune defense. Here, we demonstrate that , an important insect pathogenic fungus, modulates dominant extracellular siderophores and co-expresses the SITs and for adaptation to the host . BbMirB, but not BbMirA, is crucial for full virulence. Disruption of significantly reduces the virulence against larvae, delays immune evasion and hyphal body proliferation, and alters the host immune responses, including host nutritional immunity and immune-related gene expression. Loss of BbMirA or BbMirB leads to increased extracellular coprogen-type siderophores, including coprogen B, dimerumic acid, and their derivatives, suggesting these metabolites as their potential substrates. BbMirA and BbMirB co-localized to the plasma membrane, early/late endosomes, and vacuoles, implicating their roles in vesicular trafficking and siderophore-iron uptake. These findings highlight the importance of siderophore-iron transporters, particularly BbMirB, in fungal vesicular trafficking and host-pathogen interactions.IMPORTANCESiderophores are essential for iron uptake under iron-limiting conditions and are involved in fungal niche competition and pathogenicity via siderophore-iron transporters (SITs)-mediated uptake of specific substrates. However, the details of many SIT-mediated substrates in fungal colonization of hosts remain limited. Here, we identify two SITs, BbMirA and BbMirB, in the entomopathogenic fungus , which are highly expressed during colonization of insect hemocoel. The two SITs have complementary functions in siderophore-iron uptake , but only BbMirB dominantly mediates the uptake of a derivative of dimerumic acid and plays a critical role in the pathogenic process via disturbing insect immune defense responses. These findings provide insights into the mechanisms of SITs mediating the interaction of fungal pathogens with their hosts.
营养免疫在限制脊椎动物和无脊椎动物体内微生物病原体的增殖方面发挥着至关重要的作用。在与宿主的共同进化过程中，病原体通过铁载体 - 铁转运蛋白（SIT）介导的铁载体 - 铁螯合物摄取来获取铁，从而发展出对抗宿主营养免疫的策略。然而，关于昆虫真菌病原体的SIT在对抗宿主免疫防御中的作用知之甚少。在此，我们证明，一种重要的昆虫病原真菌，通过调节主要的细胞外铁载体并共同表达SIT 和 以适应宿主 。BbMirB而非BbMirA对 的完全毒力至关重要。 的破坏显著降低了对 幼虫的毒力，延迟了免疫逃逸和 菌丝体增殖，并改变了宿主免疫反应，包括宿主营养免疫和免疫相关基因表达。BbMirA或BbMirB的缺失导致细胞外粪卟啉型铁载体增加，包括粪卟啉B、二聚酸及其衍生物，表明这些代谢产物是它们的潜在底物。BbMirA和BbMirB共定位于质膜、早期/晚期内体和液泡，暗示它们在囊泡运输和铁载体 - 铁摄取中的作用。这些发现突出了铁载体 - 铁转运蛋白，特别是BbMirB，在真菌囊泡运输和宿主 - 病原体相互作用中的重要性。重要性铁载体在铁限制条件下对铁的摄取至关重要，并通过铁载体 - 铁转运蛋白（SIT）介导的特定底物摄取参与真菌的生态位竞争和致病性。然而，在宿主真菌定殖过程中许多SIT介导的底物细节仍然有限。在此，我们在昆虫病原真菌 中鉴定出两种SIT，BbMirA和BbMirB，它们在昆虫血腔定殖期间高度表达。这两种SIT在铁载体 - 铁摄取方面具有互补功能，但只有BbMirB主要介导二聚酸衍生物的摄取，并通过干扰昆虫免疫防御反应在致病过程中起关键作用。这些发现为SIT介导真菌病原体与其宿主相互作用的机制提供了见解。
