Uncovering the regulatory networks for Klebsiella pneumoniae iron acquisition

Iron is essential for bacterial growth, but it is severely limited in most environments. Bacteria have evolved clever systems to acquire this nutrient, including siderophores – small, high iron-affinity molecules which are secreted and then taken up in iron-bound form by surrounding bacteria. ¬¬¬The bacterial pathogen Klebsiella pneumoniae is a dangerous public health threat that produces up to four distinct siderophores. These molecules collectively determine infection routes and enable hypervirulence. Because they are essential for pathogenesis, they are also attractive therapeutic targets. Understanding how these factors are controlled could help reveal their full range of biological functions and open the way to development of new virulence-subverting drugs. This project will use an innovative “target-first” functional genomics approach to define the regulation networks that control siderophore production in different infection-relevant conditions, thus providing the first global roadmap of bacterial iron regulation. Novel regulators will then be characterised in-depth using bioinformatic approaches and molecular microbiology. This research will broaden our understanding of K. pneumoniae infections and help to establish a new technology for understanding how bacteria sense and respond to their environments. This is an interdisciplinary project encompassing genomics, functional genomics (Tn-Seq and RNAseq) and microbiology and is an excellent opportunity to train at the forefront of these disciplines. The work will be completed in collaboration with scientists at Macquarie University (Sydney) and the University of Cambridge (UK).