Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence

Abstract Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.