The phage-encoded protein PIT2 impacts quorum sensing by direct interaction with LasR.

In recent decades, there has been a notable increase in antibiotic-resistant isolates, necessitating the development of innovative treatments to combat this pathogen. This manuscript explores the potential of different phage proteins to attenuate virulence factors of , particularly the type II secretion system (T2SS). PIT2, a protein derived from the lytic phage LMA2 inhibits the T2SS effectors PrpL and LasA and attenuates the bacterial virulence toward HeLa cells and . Using RNAseq-based differential gene expression analysis, PIT2's impact on the LasR regulatory network is revealed, which plays a key role in bacterial quorum sensing. This discovery expands our knowledge on phage-encoded modulators of the bacterial metabolism and offers a promising anti-virulence target in . As such, it lays the foundation for a new phage-inspired anti-virulence strategy to combat multidrug resistant pathogens and opens the door for SynBio applications.