Pf4 infection alters P. aeruginosa virulence

Pf4 is a filamentous bacteriophage integrated as a prophage into the genome of Pseudomonas aeruginosa PAO1. Pf4 virions can be produced without killing P. aeruginosa. Cell lysis can however occur during superinfection when Pf virions successfully infect a host lysogenized by a Pf superinfective variant. We have previously shown that infection of P. aeruginosa PAO1 with a superinfective Pf4 variant led to abolish twitching motility and to alter biofilm's architecture. More precisely, the cells embedded into the biofilm were showing for most of them a filamentous morphology, that could be related to the activation of the cell envelope stress response involving both the AlgU and SigX extra cytoplasmic function sigma factors. Herein, we show that Pf4 variant-infection resulted also into a drastic dysregulation of 3,360 genes representing about 58% of P. aeruginosa's genome, of which about 43% of the virulence factors encoding genes showing a down-regulation. Accordingly, Pf4 variant infection (termed Pf4*) causes in vivo reduction of P. aeruginosa virulence, decreased production of N-acyl-homoserine lactones and 2-alkyl-4-quinolones quorum sensing molecules, and related virulence factors, such as pyocyanin, elastase, and pyoverdine. In addition to virulence encoding genes, expression of genes involved in metabolism, including energy generation and iron homeostasis, was affected, suggesting further relationships between virulence and central metabolism. Altogether, these data suggest that Pf4 phage variant infection results in complex networks dysregulations, leading to reducing acute virulence in P. aeruginosa. This work contributes to the comprehension of the bacterial response to filamentous phage infection. Overall design: Comparative gene expression profiling analysis of RNA-Seq data for Pseudomonas aeruginosa H103 (PAO1 derivative) treated or not by a superinfective Pf4 phage.