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.

生物膜是细菌采用的群落结构，包括自我形成的细胞外基质，可保护常驻细菌免受各种环境压力，并且在许多物种中，生物膜结合细胞外 DNA (eDNA) 和 DNABII 蛋白以确保整个生物膜发育过程中的结构完整性。在这里，我们提供证据表明这种基于 eDNA 的架构依赖于罕见的 Z 形。Z 型 DNA 随着生物膜的成熟而积累，并通过 DNABII 蛋白的稳定作用，赋予生物膜基质结构完整性。事实上，已知将 B-DNA 驱动到 Z-DNA 中的物质促进了生物膜的形成，而那些将 Z-DNA 驱动到 B-DNA 中的物质破坏了现存的生物膜。重要的是，我们证明了通用的细菌 DNABII 蛋白家族可以稳定 Z 型的细菌和宿主 eDNA原地。提出了一个模型，该模型结合了 Z-DNA 在生物膜发病机制、先天免疫反应和免疫逃避中的作用。