Integrated multiomics reveals starvation-driven keratin degradation and persistence in Fervidobacterium islandicum...

Keratin is one of the most recalcitrant biopolymers due to its dense disulfide crosslinks; yet, how microbial keratin degradation is regulated under nutrient limitation remains poorly understood. Here, we integrated time-resolved transcriptomics, proteomics, and metabolomics to investigate starvation-driven keratin utilization in the extremophilic bacterium Fervidobacterium islandicum AW-1. Although keratinolytic proteases are constitutively expressed, starvation induces a coordinated regulatory program that couples keratin degradation to stress adaptation. Under nutrient limitation, cells degraded keratin through localized membrane-associated proteases, while redox-mediated sulfitolysis and Fe-S cluster biogenesis facilitated disulfide bond cleavage and redox balance. Metabolic rewiring favored the Entner-Doudoroff pathway and the reverse TCA cycle, conserving energy under oligotrophic conditions. Starvation further activated the stringent response and cyclic-di-GMP-associated signaling, promoting biofilm formation, persistence-like behavior, and substrate colonization. Together, these findings propose a systems-level model linking keratin degradation to regulatory and metabolic networks that support microbial persistence in extreme environments and keratin waste valorization.