Bacteria, Phages, and Iron: Decoding the Molecular Tug-of-War in Microbial Ecosystems

About the Project

Iron is an essential nutrient for virtually all life on Earth, playing a critical role in processes such as respiration, DNA synthesis, and metabolism (1). Despite its abundance on our planet, iron bioavailability is highly limited. To overcome the nutritional limitation posed by iron scarcity, bacteria have evolved two complementary strategies: the biosynthesis of siderophores, natural products with high affinity for ferric iron, to acquire iron in oxygen-rich environments, and the deployment of ferrous iron transporters in low-oxygen environments or reducing niches. These adaptations are crucial for survival and competitiveness across diverse ecological settings, including human infections.

Intriguingly, recent studies have uncovered evidence that bacteriophages, viruses infecting bacteria, may also interact with iron metabolism, pointing to a previously underappreciated connection between phage biology and iron availability. Conserved motifs in tail fibres, which are likely to bind iron ions, have been identified in certain phages (2), and direct binding of iron to the tail structures of other bacteriophages has recently been shown (3). These findings raise the intriguing possibility that phages may influence microbial iron metabolism, either by sequestering iron through conserved binding motifs, thereby limiting its availability to host bacteria, or by exploiting iron-binding as a mechanism to enhance infection efficiency. Building on this emerging link between iron and phage biology, recent work has shown that the siderophores can sensitize bacteria to phage attack (4). This effect is mediated through iron sequestration, ultimately increasing the bacteria’s vulnerability to phage infection. These findings suggest that phages might exploit iron-related mechanisms during infection.

We hypothesize that bacteriophages interact with environmental iron through conserved iron-binding motifs, potentially influencing bacterial iron metabolism or exploiting iron-binding to enhance infection efficiency.

Aims:

Investigate the impact of phage-associated iron sequestration on bacterial iron metabolism and physiology.

Investigate how bacterial siderophore production shapes interactions with phages, influencing both competition and susceptibility to infection.

Training opportunities

The candidate will receive extensive, hands-on training and experience in microbial physiology, genetics (generation of mutant strains), phage biology and infection assays. This is complemented by comprehensive training in bioinformatics, comparative genomics and transcriptomics.

Output

• New perspectives on how iron availability shapes phage-bacteria interaction.
• Contribution to phage therapy development through mechanistic insights into iron-dependent infection dynamics, enhancing our understanding of how iron availability modulates phage efficacy and host susceptibility.

Pre-requisites

The candidate should:

• have hands-on experience in microbiology (bacteria and bacteriophages).
• be highly motivated and organized
• be fluent in English
• hold (by the start date) a Master's degree (300 ECTS credits)