A molecular comparison of [Fe-S] cluster-based homeostasis in Escherichia coli and Pseudomonas aeruginosa

Iron-sulfur [Fe-S] clusters are essential protein cofactors allowing bacteria to perceive environmental redox modification and to adapt to iron limitation. Escherichia coli, 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 Pseudomonas aeruginosa is atypical as it harbors only ISC. Here, we confirmed the essentiality of ISC in P. aeruginosa under both normal and stress conditions. Moreover, P. aeruginosa ISC restored viability, under balanced growth conditions, to an E. coli strain lacking both ISC and SUF. Reciprocally, the E. coli SUF system sustained growth and [Fe-S] cluster-dependent enzyme activities of ISC-deficient P. aeruginosa. Surprisingly, an ISC-deficient P. aeruginosa strain expressing E. coli SUF showed defects in resistance to H₂O₂ stress and paraquat, a superoxide generator. Similarly, the P. aeruginosa ISC system did not confer stress resistance to a SUF-deficient E. coli 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, P. aeruginosa shows higher fitness in the face of ROS and iron limitation than E. coli.