Analysis of co-evolutionary adaptations in bacteriophages infecting Pseudomonas aeruginosa and Klebsiella pneumoniae strains

• Grant number: 25/02846-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: João Carlos Setubal
• Grantee: Guillermo Uceda Campos
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center, AP.CEPID

Abstract

Bacteriophages (phages) are a promising alternative to combat multidrug-resistant bacteria due to their antibacterial property and host specificity1. However, this same specificity limits their application to a narrow host range. Co-evolution experiments, in which phages are exposed to both susceptible and resistant bacteria, offer a strategy to expand their host range and uncover the underlying mechanisms of host specificity, which remain poorly understood. This study aims to expand the host range of certain phages and uncover the genomic changes associated with their adaptation to Pseudomonas aeruginosa and Klebsiella pneumoniae. Phage-bacteria co-evolution experiments and validation tests will be conducted to increase the host range among strains of both species. Sampling of phage populations at multiple time points will be obtained, and the DNA in the samples will be sequenced. The analysis will identify single-nucleotide polymorphisms (SNPs) and structural variations (SVs) linked to phage adaptation. Phylogenetic trees will be constructed to trace evolutionary trajectories over the sampled time points and to identify lineages associated with specific host adaptations. Comparative genomics will highlight conserved and unique evolutionary patterns, offering critical insights into phage adaptation and guiding the possible development of phage therapy aimed at multidrug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. (AU)