Novo Nordisk Fonden - Klinisk og basal biomedicinsk forskning - How does Listeria respond to hemoglobin?

Projekter: ProjektForskning



Listeria monocytogenes is a foodborne bacterial pathogen causing life-threatening infections in susceptible individuals. This year, Listeria was the cause of a serious outbreak of listeriosis in Denmark. The outbreak caused the death of 15 patients, emphasizing the importance of improving our scientific understandings of Listeria and its pathogenic properties. Iron limitation is one of the most significant obstacles that bacteria encounter during infection. In mammalian hosts, the majority of iron is complexed to the heme subunit of hemoglobin or myoglobin, but successful pathogens, such as Listeria, may circumvent this obstacle by acquiring iron from host heme. Listeria encodes specific heme uptake systems that contribute to virulence. However, excess heme is toxic to the cell, so Listeria must regulate its accumulation very carefully. In this project we will explore how Listeria senses the presence of heme and modulates its global gene expression accordingly. Furthermore, we aim to uncover the importance of a regulatory link recently discovered by the Kallipolitis-group, between small non-coding RNAs (sRNAs) and genes
involved in heme utilization. Heme-responsive genes in Listeria – including genes encoding sRNAs – will be identified using RNA-seq. We will determine the contribution of heme-responsive genes to heme utilization, resistance to heme toxicity, and virulence in Listeria. We believe that this project will provide important information on how sRNAs contribute to the modulation of
iron acquisition from host heme during infection. These studies involve the use of molecular genetics and biochemical analyses, and infection experiments employing alternative host models. We expect to reveal novel information on how Listeria senses and responds to heme in the host environment and modulates its virulence accordingly. Ultimately, these types of studies
may lead to the discovery of novel strategies for antibacterial therapies.
Effektiv start/slut dato01/05/201530/04/2017