Non-specific interference of cobalt with siderophore-dependent iron uptake pathways

Ana Carballido Lopez (1) , Olivier Cunrath (1) , Anne Forster (1) , Julien Pérard (2) , Gwenaëlle Graulier (1) , Rachel Legendre (3, 4) , Hugo Varet (3, 4) , Odile Sismeiro (3) , Quentin Perraud (1) , Bénédicte Pesset (1) , Pamela Saint Auguste (5) , Dirk Bumann (5) , Gaetan Mislin (1) , Jean Yves Coppee (3) , Isabelle Michaud-Soret (2) , Pierre Fechter (1) , Isabelle Schalk (1)

1 BSC - Biotechnologie et signalisation cellulaire
2 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
3 PF2 - Transcriptome et Epigénome
4 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
5 Focal Area Infection Biology, Biozentrum

Much data shows that biological metals other than Fe3+ can interfere with Fe3+ acquisition by siderophores in bacteria. Siderophores are small Fe3+ chelators produced by the microorganisms to obtain access to Fe3+. Here, we show that Co2+ is imported into Pseudomonas aeruginosa cells in a complex with the siderophore pyochelin (PCH) by the ferri-PCH outer membrane transporter FptA. Moreover, the presence of Co2+ in the bacterial environment strongly affects the production of PCH. Proteomic and transcriptomic approaches showed that a decrease of PCH production is associated with repression of the expression of the genes involved in PCH biosynthesis. We used various molecular biology approaches to show that this repression is not Fur-(ferric uptake transcriptional regulator) dependent but due to competition of PCH-Co with PCH-Fe for PchR (transcriptional activator), thus inhibiting the formation of PchR-PCH-Fe and consequently the expression of the PCH genes. We observed a similar mechanism of repression of PCH production, but to a lesser extent, by Ni2+, but not for Zn2+, Cu2+, or Mn2+. Here, we show, for the first time at a molecular level, how the presence of a contaminant metal can interfere with Fe3+ acquisition by the siderophores PCH and PVD.

Domaines: Microbiologie et Parasitologie

Ana Carballido Lopez, Olivier Cunrath, Anne Forster, Julien Pérard, Gwenaëlle Graulier, et al.. Non-specific interference of cobalt with siderophore-dependent iron uptake pathways. Metallomics, 2019, 11 (11), pp.1937-1951. ⟨10.1039/C9MT00195F⟩. ⟨hal-02955479⟩