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An activator regulates the DNA damage response and anti-phage defense networks in Moraxellaceae

Shuang Song1, Shitong Zhong1, Qiucheng Shi2

  • 1MOE Key Laboratory of Biosystems Homeostasis & Protection, Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou 310016, China.

Nucleic Acids Research
|August 28, 2025
PubMed

Insights

Moraxellaceae bacteria use a novel protein, DdaA, to activate DNA damage response and anti-phage defenses, replacing the typical SOS system. This discovery aids in understanding and controlling antibiotic-resistant bacteria.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacterial Genetics

Background:

  • Antibiotics and radiation can trigger phage outbreaks in bacteria, threatening survival.
  • Moraxellaceae strains exhibit significant antibiotic and radiation resistance, making them clinically important.
  • The DNA damage response and anti-phage defense mechanisms in Moraxellaceae are poorly understood.

Purpose of the Study:

  • To investigate the cellular-level regulation of DNA damage response and anti-phage defense in Moraxellaceae.
  • To identify novel proteins involved in bacterial defense mechanisms against DNA damage and phages.

Main Methods:

  • Utilized molecular biology techniques to study gene regulation.
  • Investigated the function of a WYL family protein, DdaA.
  • Analyzed transcriptional networks under DNA damage stress.

Main Results:

  • Identified DdaA, a WYL family protein, as a key regulator in Moraxellaceae.
  • DdaA replaces the canonical SOS system in these bacteria.
  • DdaA directly activates genes involved in DNA damage response and anti-phage defense.

Conclusions:

  • DdaA plays a crucial role in enhancing bacterial immunity under DNA damage stress.
  • The findings provide insights into controlling the resistance of clinically relevant Moraxellaceae strains.

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