Bbsmf1, an Nramp Family Transporter, Sustains Iron Homeostasis Through Cross Pathway Compensation in Beauveria bassiana

Iron homeostasis is essential for the survival and pathogenesis of entomopathogenic fungi, yet the mechanisms underpinning its network resilience remain largely unknown. In this study, we characterize BbSmf1, the sole Nramp‑family transporter in the biocontrol fungus B. bassiana. Unlike the multiple paralogs found in yeast, B. bassiana possesses a streamlined Smf‑mediated pathway. We show that BbSMF1 is strongly induced under iron‑deficient conditions and is directly regulated by the core transcription factor BbHapX. Although deletion of BbSMF1 did not impair growth or virulence under standard conditions, it triggered a massive compensatory transcriptional surge-up to 109‑fold-in genes associated with the reductive iron‑uptake system (e.g., BbFREs and BbFTRs). Moreover, the ΔBbsmf1 mutant exhibited significantly reduced intracellular Fe²⁺ accumulation under severe iron‑chelation stress, positioning BbSmf1 as a critical safety valve for iron acquisition when high‑affinity uptake systems are overwhelmed. Together, these findings reveal that Bbsmf1 is a key component of a highly resilient iron‑homeostasis network, in which functional redundancy and cross‑pathway compensation ensure metabolic flexibility and survival of B. bassiana within the fluctuating nutritional environment of insect hosts. This study offers new insights into the evolutionary strategies fungal pathogens employ to maintain physiological robustness in the face of nutritional immunity.