Project

Back to the future: specificity determinant evolution of Klebsiella bacteriophage depolymerases

Code
1120125N
Duration
01 November 2024 → 31 October 2028
Funding
Research Foundation - Flanders (FWO)
Promotor
Research disciplines
  • Medical and health sciences
    • Virology
    • Microbiology not elsewhere classified
    • Bio-informatics and computational biology not elsewhere classified
    • Synthetic biology
  • Engineering and technology
    • Medical biotechnology not elsewhere classified
Keywords
Receptor-binding proteins Bacteriophages Phage Evolution
 
Project description

Bacteriophages, viruses of bacteria, are vital participants in each ecosystem, playing a key role in regulating bacterial populations. The specificity with which phages select their hosts is the current end result of a unique preceding evolutionary process. Understanding phage host specificity is essential from the ecological perspective but also provides valuable translational insights to advance phage therapy and other developments based on phage applications. In a world where the global threat posed by the rise of antimicrobial resistance is undeniable, developing new alternatives to combat multidrug-resistant infections such as phage therapy becomes increasingly essential. This project aims to unravel the molecular determinants of Klebsiella phage host specificity. In an elegant approach we will first go back to the past to learn how specificity has been diversified over time by resurrecting ancient Klebsiella phage receptor-binding proteins and evaluate them at the protein and phage level. Then we will move back to the future to regain a high specificity, capitalizing on the very rapid co-evolution process of phages and their hosts. Integrating these observations will give us a detailed and unique understanding of the determinants that shape phage host specificity. Our approach is enabled by the newest technological advancements creating unprecedented opportunities to address this fundamental question.