Acinetobacter baumannii has emerged as one of the most common extensive drug-resistant nosocomial bacterial pathogens. Not only can the bacteria survive in hospital settings for long periods, but they are also able to resist adverse conditions. However, underlying regulatory mechanisms that allow A. baumannii to cope with these conditions and mediate its virulence are poorly understood. Here, we show that bi-stable expression of the Csu pili, along with the production of poly-N-acetyl glucosamine, regulates the formation of Mountain-like biofilm-patches on glass surfaces to protect bacteria from the bactericidal effect of colistin. Csu pilus assembly is found to be an essential component of mature biofilms formed on glass surfaces and of pellicles. By using several microscopic techniques, we show that clinical isolates of A. baumannii carrying abundant Csu pili mediate adherence to epithelial cells. In addition, Csu pili suppressed surface-associated motility but enhanced colonization of bacteria into the lungs, spleen, and liver in a mouse model of systemic infection. The screening of c-di-GMP metabolizing protein mutants of A. baumannii 17978 for the capability to adhere to epithelial cells led us to identify GGDEF/EAL protein AIS_2337, here denoted PdeB, as a major regulator of Csu pili-mediated virulence and biofilm formation. Moreover, PdeB was found to be involved in the type IV pili-regulated robustness of surface-associated motility. Our findings suggest that the Csu pilus is not only a functional component of mature A. baumannii biofilms but also a major virulence factor promoting the initiation of disease progression by mediating bacterial adherence to epithelial cells.

鲍曼不动杆菌已成为最常见的广泛耐药医院细菌病原体之一。这些细菌不仅可以在医院环境中长期存活，而且还能够抵抗不利条件。然而，鲍曼不动杆菌应对这些条件并调节其毒力的潜在调控机制尚不清楚。在这里，我们发现 Csu 菌毛的双稳态表达以及聚-N-乙酰氨基葡萄糖的产生，调节玻璃表面上山状生物膜斑块的形成，以保护细菌免受粘菌素的杀菌作用。人们发现 Csu 菌毛组装是玻璃表面和薄膜上形成的成熟生物膜的重要组成部分。通过使用多种显微技术，我们表明携带丰富 Csu菌毛的鲍曼不动杆菌的临床分离株介导对上皮细胞的粘附。此外，在全身感染的小鼠模型中，Csu 菌毛抑制了表面相关的运动，但增强了细菌在肺、脾和肝脏中的定植。对鲍曼不动杆菌 17978 的 c-di-GMP 代谢蛋白突变体筛选其粘附上皮细胞的能力，使我们鉴定出 GGDEF/EAL 蛋白 AIS_2337（此处表示为 PdeB）作为 Csu 菌毛介导的毒力和生物膜的主要调节剂形成。此外，PdeB 被发现参与 IV 型菌毛调节的表面相关运动的稳健性。我们的研究结果表明，Csu 菌毛不仅是成熟鲍曼不动杆菌生物膜的功能成分，而且是通过介导细菌粘附到上皮细胞来促进疾病进展的主要毒力因子。