Abstract
When considering the interactions between bacteriophages and their host, the issue of phage-resistance emergence is a key element in understanding the ecological impact of phages on the bacterial population. It is also an essential parameter for the implementation of phage therapy to combat antibiotic-resistant pathogens. This study investigates the phenotypic and genetic responses of five Pseudomonas aeruginosa strains (PAO1, A5803, AA43, CHA, and PAK) to the infection by seven phages with distinct evolutionary backgrounds and recognised receptors (LPS/T4P). Emerging phage-insensitivity was generally accompanied by self and cross-resistance mechanisms. Significant differences were observed between the reference PAO1 responses compared to other clinical representatives. LPS-dependent phage infections in clinical strains selected for mutations in the “global regulatory” and “other” genes, rather than in the LPS-synthesis clusters detected in PAO1 clones. Reduced fitness, as proxied by the growth rate, was correlated with large deletion (20–500 kbp) and phage carrier state. Multi-phage resistance was significantly correlated with a reduced growth rate but only in the PAO1 population. In addition, we observed that the presence of prophages decreased the lytic phage maintenance seemingly protecting the host against carrier state and occasional lytic phage propagation, thus preventing a significant reduction in bacterial growth rate.
Highlights
Pseudomonas aeruginosa is one of the most genetically and phenotypically diverse species driven by frequent horizontal gene transfer (HGT), phase variation, and prophage mobility, constitutes a major health threat as an opportunistic human pathogen [1,2,3]
A thorough understanding of the factors influencing its remarkable adaptability is of critical importance, as the resistance emergence is an essential parameter to combat the increasing frequency of nosocomial infections caused by P. aeruginosa [4]
The pangenome of P. aeruginosa has been shaped by horizontal gene transfer (HGT), a process that stimulates gene circulation in the bacterial population, and in which transducing phages play a key role by mediating the transduction events
Summary
Pseudomonas aeruginosa is one of the most genetically and phenotypically diverse species driven by frequent horizontal gene transfer (HGT), phase variation, and prophage mobility, constitutes a major health threat as an opportunistic human pathogen [1,2,3]. The pangenome of P. aeruginosa has been shaped by horizontal gene transfer (HGT), a process that stimulates gene circulation in the bacterial population, and in which transducing phages play a key role by mediating the transduction events This is evident from the presence of phage genes in about 2% of the core genome and 8% among flexible and unique genes [5]. A large part of the phage-resistance mechanisms/pan-immune system is encoded within chromosomal defence islands, including CRISPR-Cas, R-M, BREX, Abi, DISARM, as well as mobile genetic elements [11,12,13]. According to this model, individual cells within the population have different combinations of defence mechanisms against different phages [13]
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