The siderophore-iron transporter BbMirB is required for the fungal pathogen to repress insect immunity and promote proliferation during colonization of hemocoel.

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.