H-NS enhances phage resistance in Klebsiella pneumoniae by suppressing quorum sensing

• Phage pressure downregulates quorum-sensing genes (luxS and lsr operon) while upregulating H-NS, linking H-NS to QS suppression. • Knockout of luxS/lsr or overexpression of H-NS reduces phage sensitivity and downregulates CPS synthase genes without altering capsular uronic acid or phage adsorption, indicating an intracellular defense mechanism. • The H-NS-QS regulatory link is conserved across hypervirulent (HvKP) and carbapenem-resistant (CRKP) strains, suggesting broad clinical relevance. • This novel mechanism offers potential targets for enhancing phage therapy against multidrug-resistant Klebsiella pneumoniae.