A molecular comparison of [Fe-S] cluster-based homeostasis in and .

UNLABELLED

Iron-sulfur [Fe-S] clusters are essential protein cofactors allowing bacteria to perceive environmental redox modification and to adapt to iron limitation. , which served as a bacterial model, contains two [Fe-S] cluster biogenesis systems, ISC and SUF, which ensure [Fe-S] cluster synthesis under balanced and stress conditions, respectively. However, our recent phylogenomic analyses revealed that most bacteria possess only one [Fe-S] cluster biogenesis system, most often SUF. The opportunist human pathogen is atypical as it harbors only ISC. Here, we confirmed the essentiality of ISC in under both normal and stress conditions. Moreover, ISC restored viability, under balanced growth conditions, to an strain lacking both ISC and SUF. Reciprocally, the SUF system sustained growth and [Fe-S] cluster-dependent enzyme activities of ISC-deficient . Surprisingly, an ISC-deficient strain expressing SUF showed defects in resistance to HO stress and paraquat, a superoxide generator. Similarly, the ISC system did not confer stress resistance to a SUF-deficient mutant. A survey of 120 Pseudomonadales genomes confirmed that all but five species have selected ISC over SUF. While highlighting the great versatility of bacterial [Fe-S] cluster biogenesis systems, this study emphasizes that their contribution to cellular homeostasis must be assessed in the context of each species and its own repertoire of stress adaptation functions. As a matter of fact, despite having only one ISC system, shows higher fitness in the face of ROS and iron limitation than .

IMPORTANCE

ISC and SUF molecular systems build and transfer Fe-S cluster to cellular apo protein clients. The model has both ISC and SUF and study of the interplay between the two systems established that the ISC system is the house-keeping one and SUF the stress-responding one. Unexpectedly, our recent phylogenomic analysis revealed that in contrast to (and related enterobacteria such as Salmonella), most bacteria have only one system, and, in most cases, it is SUF. fits the general rule of having only one system but stands against the rule by having ISC. This study aims at engineering harboring systems and vice versa. Comparison of the recombinants allowed to assess the functional versatility of each system while appreciating their contribution to cellular homeostasis in different species context.