Comparative genomic analysis of bacteriophages against Gram-negative superbugs

Antimicrobial resistance (AMR) has posed critical challenges to global health. The World Health Organization has identified carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales as the top-priority pathogens urgently to be targeted for the development of novel therapeutic options. Recently, bacteriophage therapy has attracted extensive attention owing to its potential as novel antimicrobials to combat MDR pathogens.
Bacteriophages are the most abundant and diverse organisms in the biosphere. To date, there are over 10,000 complete phage genomes in the GenBank database. Despite their relatively small genomes, bacteriophages show extraordinary genomic diversity and complex evolutionary relationships that do not follow traditional hierarchical phylogeny. The limited understanding of phage genomes and evolutionary relationship has significantly hindered the development and optimisation of effective bacteriophage therapy against ‘superbugs’.
This project will conduct comparative genomic and evolutionary analyses of bacteriophages infecting top-priority Gram-negative pathogens. The available bacteriophage genomes from public databases will be combined with our own sequenced genomes for comprehensive analysis. Evolutionary analysis for core genes will be conducted and compared with the phylogeny of host bacteria to investigate the bacteriophage-bacteria interactions in the context of coevolution. Better understanding phage genomic diversity and evolutionary conservation will facilitate the development of innovative phage therapy against the problematic ‘superbugs’.