An update on the transport and metabolism of iron in Listeria monocytogenes: the role of proteins involved in pathogenicity Original paper

What was studied?

This study focused on the transport and metabolism of iron in Listeria monocytogenes, specifically examining how the bacterium acquires and manages iron during infection. The research investigated the role of several iron transport systems, including systems for acquiring heme, ferric hydroxamate siderophores, and iron from human proteins like transferrin and ferritin. The study also analyzed the regulation of these systems by the ferric uptake regulator (Fur), highlighting their importance in Listeria pathogenesis.

Who was studied?

The study investigated Listeria monocytogenes and its iron transport and metabolism mechanisms. The research focused on bacterial strains expressing different iron acquisition systems and compared these to mutants with disrupted transport systems. Additionally, the study used mouse models to assess the impact of iron transport systems on Listeria virulence and the ability to colonize host tissues.

What were the most important findings?

The study revealed that Listeria monocytogenes utilizes multiple mechanisms for acquiring iron during infection, crucial for its survival and virulence. Key systems involved in iron uptake include the HupDCG system for heme acquisition and the FhuBCDG system for ferric hydroxamate siderophore transport. The research also identified that Listeria can utilize xenosiderophores—siderophores produced by other bacterial species. Additionally, it was found that the Fur protein, a global regulator of iron homeostasis, controls these systems, regulating genes responsible for iron uptake. Mutations in the Fur-regulated genes, such as those involved in heme and siderophore transport, resulted in significant reductions in Listeria virulence, confirming the importance of iron acquisition for pathogenesis. Moreover, the study identified a new iron acquisition pathway through the Feo transport system, highlighting its role in the bacterium’s ability to utilize ferrous iron. The presence of these systems enables Listeria to thrive in the iron-limited environment of the host, despite the host’s nutritional immunity mechanisms that sequester iron.

What are the greatest implications of this study?

The study’s findings suggest that targeting Listeria monocytogenes‘ iron acquisition systems could provide a promising approach for developing new therapeutic strategies. By disrupting iron uptake, especially through key systems like the HupDCG and FhuBCDG operons, it may be possible to limit the bacterium’s ability to infect and proliferate in the host. This approach could be particularly beneficial in managing infections in immunocompromised individuals or those undergoing treatments that impact the microbiota. Additionally, the research highlights the potential for targeting the Fur regulatory system, which governs many of these iron acquisition pathways, in designing drugs that could block Listeria‘s ability to obtain necessary nutrients for survival and virulence.