Cpe1786/IscR of Clostridium perfringens represses expression of genes involved in Fe-S cluster biogenesis.

Gaelle André (1, 2) , Elise Haudecoeur (1, 2) , Emmanuelle Courtois (1, 2) , Marc Monot (2) , Bruno Dupuy (2) , Dmitry A Rodionov (3) , Isabelle Martin-Verstraete (2, 1)

1 UPD7 - Université Paris Diderot - Paris 7
2 PBA (U-Pasteur_6) - Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes
3 Institute for Information Transmission Problems

Cpe1786 of Clostridium perfringens is an Rrf2-type regulator containing the three-cysteine residues coordinating a Fe-S in IscR, the repressor controlling Fe-S homeostasis in enterobacteria. The cpe1786 gene formed an operon with iscSU involved in Fe-S biogenesis and tmrU. This operon was transcribed from a σA-dependent promoter. We showed that in the heterologous host B. subtilis, Cpe1786 renamed IscRCp negatively controlled its own transcription. We constructed an iscR mutant in C. perfringens. We then compared the expression profile of the strain 13 and of the iscR mutant. IscRCp controlled the expression of genes involved in Fe-S biogenesis, in amino-acid or sugar metabolisms, in fermentation pathways and in host compounds utilization. We then demonstrated using a ChIP-PCR experiment that IscRCp interacted with its promoter region in vivo in C. perfringens and with the promoter of cpe2093 encoding an amino-acid ABC transporter. We utilized a comparative genomic approach to infer a candidate IscR-binding motif in clostridia and reconstruct IscR regulons in clostridia. We showed that point mutations in the conserved motif of 29 bp identified upstream of iscR decreased the cysteine-dependent repression of iscR mediated by IscRCp. Dear Editor, Please find enclosed a copy of an article entitled Cpe1786/IscR of Clostridium perfringens, represses expression of genes involved in Fe-S cluster biogenesis. This paper described the characterization of IscR in the spore former pathogen, Clostridium perfringens. We combined studies in the heterologous host Bacillus subtilis, the inactivation of iscR in C. perfringens, a comparative transcriptome analysis of the wild-type strain and of the iscR mutant and a ChIP-PCR experiment to study the role of IscR in C. perfringens. This is to our knowledge the first physiological characterization of an IscR regulator in Gram-positive bacteria. This paper is a contribution to the Special Issue of Research in Microbiology on "Beneficial and detrimental spore-formers" edited by Véronique Broussole, Christina Nielsen-Leroux, Vincent Sanchis, Frédéric Carlin and Didier Lereclus.

Mots clés: Rrf2 repressor; cysteine-dependent regulation; FeS clusters; clostridia; Fermentation

Domaines: Biologie moléculaire

Gaelle André, Elise Haudecoeur, Emmanuelle Courtois, Marc Monot, Bruno Dupuy, et al.. Cpe1786/IscR of Clostridium perfringens represses expression of genes involved in Fe-S cluster biogenesis.. Research in Microbiology, 2016, ⟨10.1016/j.resmic.2016.03.002⟩. ⟨pasteur-01370878⟩