The bacteriophage transcription factor Gp53 suppresses cell division and regulates Pseudomonas aeruginosa physiology

Abstract Pseudomonas aeruginosa is a highly drug-resistant pathogen that poses a major challenge to clinical treatment. Bacteriophages encode diverse regulatory proteins that can alter host cellular processes during infection. Here we show that the ΦPA1019-encoded transcription factor Gp53 regulates bacterial physiology by targeting key host pathways. Gp53 expression reduces bacterial growth, motility, and biofilm formation, and causes filamentous cell morphology. Transcriptomic analysis reveals that Gp53 alters the expression of 3,342 genes, including genes involved in cell division and virulence-associated processes. DNA-binding assays demonstrate that Gp53 directly represses promoters of key host genes, including ftsZ , fleQ , pslA , and amrZ . Gp53-mediated repression of ftsZ disrupts Z-ring formation and inhibits cell division, while ftsZ expression restores these defects. Structural and mutational analyses identify residues important for Gp53-DNA interaction. Together, these findings reveal a phage-encoded mechanism that coordinately interferes with bacterial cell division and virulence-associated pathways, providing mechanistic insights into host transcriptional regulation during phage infection and expanding our understanding of phage-host interactions.