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Identification and biosynthesis of a novel thymidine hypermodification Na-dapT in Acinetobacter baumannii phage SH-Ab 15599

ABSTRACT: Bacteriophage genomes exhibit exceptional diversity in nucleobase modifications, which primarily function to counteract host immunity and reshape DNA physicochemical properties. Recent discoveries of aGPT-Pplase2-catalyzed novel thymidine hypermodifications reveal a broader enzymatic and chemical diversity in phage DNA modification systems. However, the diversity of thymidine hypermodification in other bacteriophages remains largely unexplored. Here we discovered a novel thymidine hypermodification, Na-dapT, in the Acinetobacter baumannii phage SH-Ab 15599, and elucidated its biosynthetic pathway, including the key diamine DNA transferase (DADT, formerly aGPT-Pplase2). DADT utilizes the abundant metabolite 1,3-diaminopropane of host to modify 5hmdU-DNA, exhibiting broad in vitro substrate specificity but a strong in vivo preference for 1,3-diaminopropane. Structural and mutagenesis analyses revealed the molecular basis for substrate recognition and catalysis. The Na-dapT modification occurs specifically at TG dinucleotides and confers resistance to multiple host restriction enzymes, enabling phage escape from the host restriction-modification system. Furthermore, RNA-seq analysis showed that phage infection reprograms host metabolism, upregulating genes for 1,3-diaminopropane synthesis to supply the modification precursor. Our study identified SH-Ab 15599 DADT as a versatile enzyme responsible for thymidine hypermodification, and comprehensively describes a viral strategy of exploiting host metabolites for DNA modification to evade bacterial defense.

ORGANISM(S): Acinetobacter phage SH-Ab 15599

PROVIDER: GSE322957 | GEO | 2026/03/05

REPOSITORIES: GEO

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Identification and biosynthesis of a novel thymidine hypermodification Na-dapT in Acinetobacter baumannii phage SH-Ab 15599

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