title: The iron-binding CyaY and IscX proteins assist the ISC-catalyzed Fe-S biogenesis in Escherichia coli.
abstract: In eukaryotes, frataxin deficiency (FXN) causes severe phenotypes including loss of iron-sulfur (Fe-S) cluster protein activity, accumulation of mitochondrial iron and leads to the neurodegenerative disease Friedreich's ataxia. In contrast, in prokaryotes, deficiency in the FXN homolog, CyaY, was reported not to cause any significant phenotype, questioning both its importance and its actual contribution to Fe-S cluster biogenesis. Because FXN is conserved between eukaryotes and prokaryotes, this surprising discrepancy prompted us to reinvestigate the role of CyaY in Escherichia coli. We report that CyaY (i) potentiates E. coli fitness, (ii) belongs to the ISC pathway catalyzing the maturation of Fe-S cluster-containing proteins and (iii) requires iron-rich conditions for its contribution to be significant. A genetic interaction was discovered between cyaY and iscX, the last gene of the isc operon. Deletion of both genes showed an additive effect on Fe-S cluster protein maturation, which led, among others, to increased resistance to aminoglycosides and increased sensitivity to lambda phage infection. Together, these in vivo results establish the importance of CyaY as a member of the ISC-mediated Fe-S cluster biogenesis pathway in E. coli, like it does in eukaryotes, and validate IscX as a new bona fide Fe-S cluster biogenesis factor.
authors.affiliation: Laboratoire de Chimie Bactérienne, UMR 7283, Aix-Marseille Université-CNRS, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009, Marseille, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Roche
authors.forename: Allison
authors.initials: A
authors.lastname: Huguenot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Barras
authors.forename: Béatrice
authors.initials: B
authors.lastname: Py
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D010582:Bacteriophage lambda / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D056084:Genetic Fitness; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D009154:Mutation; D009876:Operon; D013455:Sulfur / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; C120906:CyaY protein, E coli; D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; C510279:IscX protein, E coli; D013455:Sulfur; D007501:Iron