ABSTRACT.- Heme and iron metabolic pathways are highly intertwined, both compounds being essential for key biological processes, yet becoming toxic if overabundant.Their concentrations are exquisitely regulated, including via dedicated two-component systems (TCSs) that sense signals and regulate adaptive responses.HemKR is a TCS present in both saprophytic and pathogenic Leptospira species, involved in the control of heme metabolism.However, the molecular means by which HemKR is switched on/off in a signal-dependent way, are still unknown.Moreover, a comprehensive list of HemKR-regulated genes, potentially overlapped with iron-responsive targets, is also missing. © 2024 Imelio et al.