Bacteriophages hijack 2',3'-cNMPs to enhance transposase-mediated phage DNA integration in <i>Acinetobacter baumannii</i>.

Cui, Binbin; Ling, Xiwen; Peng, Ganjin; Guo, Quan; Kong, Xiaohan; Wang, Rixiang; Ma, Yingfei; Deng, Pujuan et al. · Sci Adv · 2026

basic_science · Level V

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Abstract

Nucleotide second messengers are widely used to mediate the physiology and antiphage immunity in bacteria. It was revealed that 2',3'-cAMP/2',3'-cGMP synthetase activity is required for immune response in plants. However, it remains unclear whether 2',3'-cNMPs are involved in the interactions between bacteria and phages. Here, we report that 2',3'-cNMPs, which are synthesized by RnaA and degraded by A1S_2339, A1S_0249, and A1S_2666, play critical roles in the modulation of the physiology of <i>Acinetobacter baumannii</i>. 2',3'-cNMPs specifically bind to the receptor protein CRP<sub>Ab</sub> in <i>A. baumannii</i> and thus affect the interaction between CRP<sub>Ab</sub> and the promoters of target genes. Furthermore, our study reveals that bacteriophages elevate 2',3'-cNMPs to up-regulate the transcription of the transposases and Mu-like integrases required for bacteriophage DNA integration. Together, our results show that 2',3'-cNMPs are important intracellular signals that control biological functions of <i>A. baumannii</i>, and bacteriophages could hijack these signals to facilitate phage DNA integration.

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