Department of Science, Roma Tre University, Rome, Italy.
Department of Microbiology, Stress Adaptation and Metabolism Unit, UMR CNRS 6047, Université Paris-Cité, Institut Pasteur, Paris, France.
mBio. 2024 Nov 13;15(11):e0120624. doi: 10.1128/mbio.01206-24. Epub 2024 Oct 3.
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 .
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.
铁硫 [Fe-S] 簇是必不可少的蛋白质辅因子，使细菌能够感知环境氧化还原修饰并适应铁限制。作为细菌模型，含有两个 [Fe-S] 簇生物发生系统，ISC 和 SUF，分别确保在平衡和应激条件下 [Fe-S] 簇的合成。然而，我们最近的系统发育基因组分析显示，大多数细菌只拥有一个 [Fe-S] 簇生物发生系统，通常是 SUF。机会主义人类病原体 是一个特例，因为它只拥有 ISC。在这里，我们在正常和应激条件下证实了 ISC 在 中的必要性。此外，ISC 在平衡生长条件下恢复了缺乏 ISC 和 SUF 的 菌株的活力。相反，SUF 系统维持了 ISC 缺陷型 的生长和 [Fe-S] 簇依赖的酶活性。令人惊讶的是，表达 SUF 的 ISC 缺陷型 菌株在 HO 应激和百草枯（一种超氧化物产生剂）的抗性方面表现出缺陷。同样，ISC 系统也不能赋予 SUF 缺陷型 突变体应激抗性。对 120 种假单胞菌目基因组的调查证实，除了 5 个种之外，所有种都选择了 ISC 而不是 SUF。本研究突出了细菌 [Fe-S] 簇生物发生系统的巨大多功能性，同时强调了在每种物种及其自身的应激适应功能的背景下，评估其对细胞内稳态的贡献的必要性。事实上，尽管只有一个 ISC 系统， 但在面对 ROS 和铁限制时比 表现出更高的适应性。
ISC 和 SUF 分子系统构建并将 Fe-S 簇转移到细胞 apo 蛋白客户中。模型 同时拥有 ISC 和 SUF，对两者系统相互作用的研究确立了 ISC 系统是管家系统，SUF 系统是应激响应系统。出乎意料的是，我们最近的系统发育基因组分析显示，与 （和相关的肠杆菌科，如沙门氏菌）相反，大多数细菌只拥有一个系统，而且在大多数情况下，这个系统是 SUF。 符合只拥有一个系统的一般规律，但它通过拥有 ISC 而违反了这一规律。本研究旨在构建同时拥有 ISC 和 SUF 系统的 工程菌株和反之亦然。比较重组体允许评估每个系统的功能多功能性，同时欣赏它们在不同物种背景下对细胞内稳态的贡献。
