ABSTRACT
Ironsulfur (Fe-S) clusters are one of the most ancient and versatile inorganic cofactors present in the three domains of life. Fe-S clusters are essential cofactors for the activity of a large variety of metalloproteins that play crucial physiological roles. Fe-S protein biogenesis is a complex process that starts with the acquisition of the elements (iron and sulfur atoms) and their assembly into an Fe-S cluster that is subsequently inserted into the target proteins. The Fe-S protein biogenesis is ensured by multiproteic systems conserved across all domains of life. Here, we provide an overview on how bacterial genetics approaches have permitted to reveal and dissect the Fe-S protein biogenesis process in vivo.
Subject(s)
Bacterial Proteins , Iron-Sulfur Proteins , Iron-Sulfur Proteins/metabolism , Iron-Sulfur Proteins/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Iron/metabolism , Sulfur/metabolism , Bacteria/genetics , Bacteria/metabolismABSTRACT
Myxococcus xanthus possesses two Fe-S cluster biogenesis machineries, ISC (iron-sulfur cluster) and SUF (sulfur mobilization). Here, we show that in comparison to the phylogenetically distant Enterobacteria, which also have both machineries, M. xanthus evolved an independent transcriptional scheme to coordinately regulate the expression of these machineries. This transcriptional response is directed by RisR, which we show to belong to a phylogenetically distant and biochemically distinct subgroup of the Rrf2 transcription factor family, in comparison to IscR that regulates the isc and suf operons in Enterobacteria. We report that RisR harbors an Fe-S cluster and that holo-RisR acts as a repressor of both the isc and suf operons, in contrast to Escherichia coli, where holo-IscR represses the isc operon whereas apo-IscR activates the suf operon. In addition, we establish that the nature of the cluster and the DNA binding sites of RisR, in the isc and suf operons, diverge from those of IscR. We further show that in M. xanthus, the two machineries appear to be fully interchangeable in maintaining housekeeping levels of Fe-S cluster biogenesis and in synthesizing the Fe-S cluster for their common regulator, RisR. We also demonstrate that in response to oxidative stress and iron limitation, transcriptional upregulation of the M. xanthus isc and suf operons was mediated solely by RisR and that the contribution of the SUF machinery was greater than the ISC machinery. Altogether, these findings shed light on the diversity of homeostatic mechanisms exploited by bacteria to coordinately use two Fe-S cluster biogenesis machineries. IMPORTANCE Fe-S proteins are ubiquitous and control a wide variety of key biological processes; therefore, maintaining Fe-S cluster homeostasis is an essential task for all organisms. Here, we provide the first example of how a bacterium from the Deltaproteobacteria branch coordinates expression of two Fe-S cluster biogenesis machineries. The results revealed a new model of coordination, highlighting the unique and common features that have independently emerged in phylogenetically distant bacteria to maintain Fe-S cluster homeostasis in response to environmental changes. Regulation is orchestrated by a previously uncharacterized transcriptional regulator, RisR, belonging to the Rrf2 superfamily, whose members are known to sense diverse environmental stresses frequently encountered by bacteria. Understanding how M. xanthus maintains Fe-S cluster homeostasis via RisR regulation revealed a strategy reflective of the aerobic lifestyle of this organsim. This new knowledge also paves the way to improve production of Fe-S-dependent secondary metabolites using M. xanthus as a chassis.
Subject(s)
Escherichia coli Proteins , Iron-Sulfur Proteins , Myxococcus xanthus , Escherichia coli Proteins/metabolism , Myxococcus xanthus/genetics , Myxococcus xanthus/metabolism , Gene Regulatory Networks , Escherichia coli/genetics , Iron/metabolism , Sulfur/metabolism , Iron-Sulfur Proteins/chemistryABSTRACT
TITLE: Les bactéries, organismes de choix pour comprendre les mécanismes de réparation des protéines oxydées. ABSTRACT: Dans le cadre de l'unité d'enseignement « Rédiger en sciences ¼ proposée par l'université d'Aix-Marseille, les étudiants du Master 2 de microbiologie se sont confrontés aux exigences de l'écriture scientifique. Quatre thématiques leur ont été proposées : les virus géants, les systèmes de sécrétion, la motilité bactérienne et la réparation des protéines oxydées. Après un travail préparatoire effectué avec l'équipe pédagogique et les auteurs des publications originales, les étudiants, organisés en groupes de trois ou quatre, ont rédigé une Nouvelle soulignant les résultats majeurs et l'originalité des quatre articles étudiés. Complété par un entretien avec les chercheurs auteurs de ces articles, l'ensemble offre un éclairage original sur la compréhension du vivant dans le domaine de la microbiologie.