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<p>Natural transformation drives the spread of antibiotic resistance among bacteria. The DNA receptor ComEA is essential for transporting external transforming DNA into the periplasm by an unknown mechanism. Here, single-molecule optical tweezers and electron microscopy approaches show that <i>Geobacillus stearothermophilus</i> ComEA forms dynamic oligomers on DNA that can switch between two conformations depending on local concentration. When ComEA sparsely decorates DNA, it forms bridging oligomers that condense the DNA to generate sub-pN pulling forces. When ComEA more fully decorates DNA, it forms non-bridging oligomers that decondense DNA and cannot generate force. Mutating ComEA to favor either bridging or non-bridging conformations causes transformation deficiency in <i>Bacillus subtilis</i>, meaning condensation and decondensation each play mechanistic roles. Our results show that ComEA reversibly condenses DNA during natural transformation, first producing force to pull DNA into the periplasm and then abating force production to promote transport into the cytoplasm.</p>

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Reversible DNA condensation drives natural transformation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月19日

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  • Joshua I. Santiago,
  • Ishtiyaq Ahmed,
  • Jeanette Hahn,
  • Abigail Rubino,
  • Heonhwa Choi,
  • Guy Adami,
  • David Dubnau,
  • Matthew B. Neiditch,
  • Keith J. Mickolajczyk

摘要

Natural transformation drives the spread of antibiotic resistance among bacteria. The DNA receptor ComEA is essential for transporting external transforming DNA into the periplasm by an unknown mechanism. Here, single-molecule optical tweezers and electron microscopy approaches show that Geobacillus stearothermophilus ComEA forms dynamic oligomers on DNA that can switch between two conformations depending on local concentration. When ComEA sparsely decorates DNA, it forms bridging oligomers that condense the DNA to generate sub-pN pulling forces. When ComEA more fully decorates DNA, it forms non-bridging oligomers that decondense DNA and cannot generate force. Mutating ComEA to favor either bridging or non-bridging conformations causes transformation deficiency in Bacillus subtilis, meaning condensation and decondensation each play mechanistic roles. Our results show that ComEA reversibly condenses DNA during natural transformation, first producing force to pull DNA into the periplasm and then abating force production to promote transport into the cytoplasm.