Honghua Ge

The qatABCD system is a widespread anti-phage module featuring a core QatBC complex, but the specific biological role of its conserved component, QatD, has long been enigmatic. Here, we establish QatD is a TatD-family nuclease co-opted for antiviral defense. The crystal structure of Acinetobacter baumannii QatD reveals a classic TIM-barrel fold featuring a conserved “HxH” active-site motif characteristic of Type II TatD enzymes. Biochemically, QatD exhibits metal-dependent dual activity: a Mg2+-dependent 3′-5′ exonuclease and a Ca2+-dependent apurinic/apyrimidinic (AP) endonuclease. We further demonstrate that QatD confers resistance against diverse bacteriophages in vivo, suggesting its defense function is tied to its catalytic activity. Crucially, we discovered that the nuclease activity of QatD is tightly inhibited by physiological concentrations of host nucleoside triphosphates (NTPs). Based on these findings, we propose a mechanistic model wherein the massive nucleotide consumption during rapid viral transcription and replication depletes local host NTP pools, thereby relieving the metabolic inhibition on QatD. The unleashed QatD subsequently targets and degrades single-stranded replication intermediates and AP-site-containing viral genomes. Our work not only elucidates the molecular basis of QatD activation but also highlights an elegant evolutionary strategy wherein bacteria couple metabolic sensing with ancient DNA repair machinery for specialized immune defense.

Legionella pneumophila , the causative agent of Legionnaires’ disease, utilizes a type IV secretion system (T4SS) to translocate effectors into host cells, modulating diverse cellular processes to create a replication-permissive niche. Here, we characterize Ceg10, a T4SS-translocated effector, as a nucleus-targeting acetyltransferase that interferes with host ribosome biogenesis and cell cycle progression. Structural analysis reveals that Ceg10 harbors a conserved Cys-His-Asp (CHD) catalytic triad required for its acetyltransferase activity. Upon nuclear import mediated by the host transport adaptor HEATR3, Ceg10 selectively acetylates the ribosomal protein RPS20 at Thr64, Thr65, and Arg66, which have not been annotated as posttranslational modification sites. This acetylation impairs RPS20’s interaction with RPS29 and 18S rRNA, two components critical for 40S ribosomal subunit assembly, leading to translation inhibition and G1/S cell cycle arrest. These host perturbations are essential for efficient early-stage intracellular replication of L. pneumophila . Our findings identify a distinct mechanism by which a bacterial effector co-opts nuclear import machinery and directly modifies ribosomal proteins to subvert host biosynthesis and cell cycle control, highlighting ribosomal protein acetylation as a hitherto unrecognized role in host–pathogen interactions.