The importance of NO

Oeiras, 12.11.09

Marta C. Justino, post-doc at the Molecular Genetics of Microbial Resistance Lab, received the “Prix Jeunes Chercheurs” for her oral presentation “Ric proteins – A novel system for repair of nitrosatively and oxidatively damaged Fe-S clusters” during the “Congrès 2009 du Club NO” in Paris in October.

The Club NO France is an association which aims to further and promote all knowledge related to nitric oxide in both fundamental and applied sciences. It organises meetings and offers grants to exceptional students, post-docs and principal investigators. It is fast becoming the most useful resource for all nitric oxide researchers from all over the world. Among the 60 participants attending the “Congrès 2009 du Club NO", two “Prix Jeunes Chercheurs” were attributed by the Club NO Board Members.

Ric proteins – A novel system for repair of nitrosatively and oxidatively damaged Fe-S clusters

Marta C. Justino, Joana M. Baptista and Lígia M. Saraiva

Introduction:  Nitric oxide is produced by the mammalian immune system and plays a key role in the defence against invading pathogens. Nitric oxide and concomitant reactive nitrogen species cause damage to nearly all types of the pathogens cellular components, including lipids, DNA and proteins. To counter-act the effects of the immune system attack, bacteria possess several systems that allow the detoxification of reactive species and promote the repair of the caused damages, such as DNA repair enzymes.
One major target of NO reactivity is the proteins with iron-sulphur centres, which are essential for a wide range of biological processes, because of their involvement in electron transfer chains, gene regulation and environmental sensing. Despite the evidence sustaining the occurrence of Fe-S cluster repair, the systems involved were sill poorly known.

Résultats: In the present work we show that three homologous proteins from the distantly related pathogens Staphylococcus aureus, Neisseria gonorrhoeae and Escherichia coli can protect their hosts from damage caused by exposure to nitric oxide and also hydrogen peroxide. The phenotypic studies with mutant strains revealed that, in the absence of the S. aureus scdA gene, of the gonoccocal dnrN gene and of the E. coli ytfE gene, housekeeping enzymes and transcription factors containing iron-sulphur clusters suffer more intense nitrosative and oxidative damage, which we demonstrate to be associated with the severe impairment of the repair of Fe-S clusters. Moreover, we show that the ScdA and YtfE proteins contain a di-iron centre and that addition of these proteins to cell extracts that were exposed to oxidative and nitrosative stress promotes the repair of both oxidatively and nitrosatively iron-sulphur clusters.

Conclusions:  In conclusion, we present evidence for a novel family of proteins that are able to repair Fe-S clusters damaged by reactive oxygen and nitrogen species. These proteins are widely spread in nature and have high incidence in human pathogens, both in Gram-positive and Gram-negative, and have been named Repair of Iron Centers (RIC) proteins.