How does Listeria respond to hemoglobin?

Project: Research

Project Details


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.
Effective start/end date01/05/201530/04/2017