Bacteriophages hijack 2′,3′-cNMPs to enhance transposase-mediated phage DNA integration in Acinetobacter baumannii
- Binbin Cui
- Xiwen Ling
- Ganjin Peng
- Quan Guo
- Xiaohan Kong
- Rixiang Wang
- Yingfei Ma
- Pujuan Deng
- Hua Cai
- Xiaoxue Wang
- Yinyue Deng
2026-06-12
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 Acinetobacter baumannii . 2′,3′-cNMPs specifically bind to the receptor protein CRP Ab in A. baumannii and thus affect the interaction between CRP Ab 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 A. baumannii , and bacteriophages could hijack these signals to facilitate phage DNA integration.