Z-form extracellular DNA is a structural component of the bacterial biofilm matrix

Cell. 2021 Nov 11;184(23):5740-5758.e17. doi: 10.1016/j.cell.2021.10.010. Epub 2021 Nov 3.

Abstract

Biofilms are community architectures adopted by bacteria inclusive of a self-formed extracellular matrix that protects resident bacteria from diverse environmental stresses and, in many species, incorporates extracellular DNA (eDNA) and DNABII proteins for structural integrity throughout biofilm development. Here, we present evidence that this eDNA-based architecture relies on the rare Z-form. Z-form DNA accumulates as biofilms mature and, through stabilization by the DNABII proteins, confers structural integrity to the biofilm matrix. Indeed, substances known to drive B-DNA into Z-DNA promoted biofilm formation whereas those that drive Z-DNA into B-DNA disrupted extant biofilms. Importantly, we demonstrated that the universal bacterial DNABII family of proteins stabilizes both bacterial- and host-eDNA in the Z-form in situ. A model is proposed that incorporates the role of Z-DNA in biofilm pathogenesis, innate immune response, and immune evasion.

Keywords: DNABII proteins; DNase resistance; Z-DNA; biofilm matrix; extracellular DNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Specificity
  • Bacteria / genetics*
  • Bacterial Proteins / metabolism
  • Biofilms*
  • Cell Line
  • Chinchilla
  • DNA, Bacterial / chemistry*
  • DNA, Cruciform
  • Deoxyribonucleases / metabolism
  • Extracellular Matrix / metabolism*
  • Extracellular Space / chemistry*
  • Extracellular Traps / metabolism
  • Humans
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • DNA, Cruciform
  • Deoxyribonucleases
  • Tetradecanoylphorbol Acetate