Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2024

Evolutionary And Coevolutionary Phage Training Approaches Enhance Bacterial Suppression And Delay The Emergence Of Phage Resistance (103880)

Lyman Ngiam 1 , Kaz Weynberg 1 , Jianhua Guo 2
  1. Centre for Environmental and Agricultural Solutions to Antimicrobial Resistance, St Lucia, QLD, Australia
  2. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia, Australian Centre for Ecogenomics, Brisbane, QLD, Australia

The development of phage resistance by bacteria is a major barrier that impedes the therapeutic use of phage. Phage training has been proposed as a novel tool that harnesses the evolutionary potential of phage to improve phage infectivity. Both evolutionary and coevolutionary phage training models have been adopted to train phage. However, it is unclear how both evolutionary and coevolutionary phage training models affect phage physiology and its subsequent infectivity. In this study, phage infecting Klebsiella pneumonia strain was isolated and subjected to evolutionary and coevolutionary phage training for 30 days. Post phage training, the physiology and genomic characteristics of evolved and coevolved phage were assessed. From the results, evolved phages were found to have improved infectivity and phage population kinetic dynamics compared to coevolved phage. Furthermore, both evolved and coevolved phage were found to harbor unique genome mutational changes in different functionally associated phage proteins. Similarly, evolved and coevolved phage resistant bacteria mutants that arise post infection were also found to have varying genome mutational change and varying phage resistance dynamics. Particularly, coevolved phage resistant bacteria mutants were found to have less resistance against other tested phage when compared to evolved phage resistant bacteria mutants. Our results highlighted that coevolutionary phage training model serves as a better phage training model that endow phage with improved infectivity and delays the emergence of phage resistant bacteria mutants with lower resistance sensitivity.