DNA Methyltransferase regulates type III secretion system and virulence in a chronically adapted Pseudomonas aeruginosa strain

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen commonly found in lung infections that cause morbidity and mortality, particularly in severe infection requiring ventilation like COVID-19. Although a long battery of virulence factors on adapted genomes is always a concern, the epigenetics of P. aeruginosa is still lacking. Toxins are often secreted by different types of protein secretion systems, of which the type III secretion system (T3SS) is one of the major contributors to the potential virulence system. However, there is currently limited evidence regarding the epigenetic regulation of bacterial T3SS. Previous study characterized a P. aeruginosa clinical strain LYSZa7 from a COVID-19 patient, which carried specific GIs for R-M systems and may result in DNA methylation. This study investigated the regulatory effect of a DNA methyltransferase, PaeZa7Mod, which belongs to the type III RM system. We verified the function of the type III RM system and demonstrated that PaeZa7Mod regulates the T3SS gene clusters and affects bacterial virulence.