Bacterial infections lead to high morbidity and mortality globally. While current therapies against bacteria often employ antibiotics, most bacterial pathogens can form biofilms and prevent effective treatment of infections. Biofilm cells can aggregate and encased themselves in a self‐secreted protective exopolymeric matrix, to reduce the penetration by antibiotics. Biofilm formation is mediated by c‐di‐GMP signaling, the ubiquitous secondary messenger in bacteria. Synthesis of c‐di‐GMP by diguanylate cyclases leads to biofilm formation via the loss of motility, increased surface attachment, and production of biofilm matrix, whereas c‐di‐GMP degradation by phosphodiesterases causes biofilm dispersal to new sites via increased bacterial motility and matrix breakdown. The highly variable nature of biofilm development and antimicrobial tolerance imposes tremendous challenges in conventional antimicrobial therapies, indicating an imperative need to develop anti‐biofilm drugs against biofilm infections. In this review, we focus on two main emergent approaches—active dispersal and disruption. While both approaches aim to demolish biofilms, we will discuss their fundamental differences and associated methods. Active dispersal of biofilms involves signaling the bacterial cells to leave the biofilm, where resident cells ditch their sessile lifestyle, gain motility and self‐degrade their matrix. Biofilm disruption leads to direct matrix degradation that forcibly releases embedded biofilm cells. Without the protection of biofilm matrix, released bacterial cells are highly exposed to antimicrobials, leading to their eradication in biofilm infections. Understanding the advantages and disadvantages of both approaches will allow optimized utility with antimicrobials in clinical settings.

中文翻译：

---

拆除革兰氏阴性菌生物膜的长城：破坏还是分散？

细菌感染导致全球高发病率和死亡率。虽然目前针对细菌的疗法通常使用抗生素，但大多数细菌病原体可以形成生物膜并阻止对感染的有效治疗。生物膜细胞可以聚集并包裹在自我分泌的保护性外聚合基质中，以减少抗生素的渗透。生物膜的形成是由 c-di-GMP 信号介导的，c-di-GMP 是细菌中普遍存在的二级信使。双鸟苷酸环化酶合成 c-di-GMP 通过失去运动性、增加表面附着和产生生物膜基质导致生物膜形成，而磷酸二酯酶降解 c-di-GMP 通过增加细菌运动和矩阵分解。生物膜发展和抗菌耐受性的高度可变性给传统抗菌疗法带来了巨大挑战，这表明迫切需要开发针对生物膜感染的抗生物膜药物。在这篇评论中，我们关注两种主要的紧急方法——主动分散和破坏。虽然这两种方法都旨在拆除生物膜，但我们将讨论它们的根本区别和相关方法。生物膜的主动扩散涉及向细菌细胞发出离开生物膜的信号，在生物膜中，常驻细胞摆脱固着的生活方式，获得运动能力并自我降解它们的基质。生物膜破坏导致直接基质降解，强行释放嵌入的生物膜细胞。没有生物膜基质的保护，释放的细菌细胞高度暴露于抗菌剂，导致它们在生物膜感染中被根除。了解这两种方法的优缺点将有助于优化抗菌药物在临床环境中的效用。