Crosstalk between inovirus core gene and accessory toxin-antitoxin system mediates polylysogeny

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Polylysogeny, harboring multiple prophages, is prevalent in bacterial pathogens, influencing virulence and genome plasticity.
• Inoviruses, like Pf4 and Pf6 in Pseudomonas aeruginosa, often exist in multiple copies, contributing to polylysogeny and phage activation during biofilm formation.

Purpose of the Study:

• To investigate the interaction between two co-resident filamentous phages, Pf4 and Pf6, within Pseudomonas aeruginosa.
• To elucidate the molecular mechanisms governing the cooperative or competitive behavior of these prophages.

Main Methods:

• Investigated the crosstalk between Pf4's RepG4 protein and Pf6's KKP toxin-antitoxin module.
• Analyzed the dose-dependent effects of RepG4 on KKP-mediated toxicity and antitoxin degradation.

Main Results:

• Demonstrated a crosstalk between Pf4's RepG4 and Pf6's KKP module, coordinating phage propagation.
• RepG4 triggers kinase-mediated toxicity of KKP by degrading the antitoxin, acting as a molecular brake on Pf4 production.
• This regulation coordinates the release of both Pf4 and Pf6 phages during biofilm maturation.

Conclusions:

• The study reveals a novel regulatory crosstalk between phage core and accessory genes.
• This interaction establishes a mutualistic relationship between co-resident prophages, crucial for their propagation in bacterial hosts.
• Findings offer insights into the complex dynamics of polylysogeny in bacterial pathogens.