# Unravelling the noncanonical extracellular DNA structures in biofilm and NETosis

## TL;DR

This paper explores the role of noncanonical DNA structures in biofilms and NETs, suggesting they may influence disease and immunity.

## Contribution

The paper advocates for investigating noncanonical extracellular DNA structures in dynamic environments for their impact on microbial and immune processes.

## Key findings

- Noncanonical DNA structures are found in biofilms and NETs, contributing to structural stability and antimicrobial activity.
- These structures may influence microbial behavior, immune responses, and host-pathogen interactions.
- Targeting these DNA structures could lead to new therapeutic strategies for diseases involving biofilms and NETs.

## Abstract

Noncanonical secondary structures of DNA have been well characterized in vitro for their catalytic and sensory functions, as well as in vivo for their regulatory functions in the genome. However, their presence and functional significance in the extracellular DNA (eDNA), particularly within biofilms and neutrophil extracellular traps (NETs), have only recently begun to be appreciated and have yet to be fully understood. Emerging studies have identified these atypical DNA conformations as integral components that contribute to the structural stability of biofilms and antimicrobial activity of NETs. In this personal view, we advocate for a comprehensive investigation of these unconventional DNA structures within extracellular contexts, where their distinct physiochemical properties are exposed to dynamic and unpredictable microenvironments, with the potential to profoundly influence microbial behaviour, immune responses, and host–pathogen interactions. Considering the broad spectrum of diseases associated with biofilm and NETs, targeting noncanonical eDNA structures may offer novel therapeutic avenues and shed light on mechanisms of immune tolerance and dysregulation.

Graphical Abstract