[SCAN] An RNA-based approach to bacterial infection: PNPase controls iron metabolism and virulence in the human pathogen Listeria

Title: An RNA-based approach to bacterial infection: PNPase controls iron metabolism and virulence in the human pathogen Listeria

Speaker: José Andrade

Affiliation: Cecília Arraiano Lab

Listeria monocytogenes is a facultative intracellular pathogen, responsible for severe foodborne infections in humans. To establish and maintain a successful infection, Listeria has evolved sophisticated regulatory pathways including post-transcriptional mechanisms. PNPase is a conserved exoribonuclease that is a major enzyme involved in the degradation of RNA. We found that inactivation of PNPase leads to the strong attenuation of Listeria pathogenicity, however, the underlying mechanism for this phenotype was elusive.

Transcriptomic analysis revealed that PNPase affects a large set of genes involved in iron transport and metabolism. This result shows high similarities to the regulon controlled by the transcriptional repressor Fur (Ferric uptake regulator), the master regulator of iron metabolism in bacteria. Further analysis showed that PNPase regulates Fur levels with inactivation of PNPase leading to the reduced expression of Fur levels. Strikingly, PNPase was found to degrade a set of non-coding RNAs (ncRNAs) that vary their levels according to the iron content in the cell. The molecular characterisation of these ncRNAs revealed their ability to base pair with fur mRNA and one of these ncRNAs was very effective in repressing fur translation in vivo. The network mediated by PNPase/ncRNA/fur is a novel post-transcriptional pathway of iron homeostasis.

Our work identified a new function of PNPase in the regulation of a unique metabolic pathway relevant for bacterial virulence, as iron is an essential nutrient required for infection by many pathogens. Accordingly, the imbalance of iron metabolism contributes to the strong attenuation of virulence found in the Listeria PNPase mutant.