Yu Lumin, Wang Hui, Zhang Xinglin, Xue Ting
College of Agriculture and Forestry, Linyi University, Linyi, Shandong 276000, China.
College of Agriculture and Forestry, Linyi University, Linyi, Shandong 276000, China; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China.
Poult Sci. 2025 Aug 24;104(11):105726. doi: 10.1016/j.psj.2025.105726.
Avian pathogenic Escherichia coli (APEC) is a widespread bacterial pathogen that poses a significant threat to the poultry industry globally. It is of great significance to control APEC infections by investigating the molecular mechanisms that regulate APEC's adaptation to new environments and its survival. APEC possesses a series of regulation systems to sense and quickly and appropriately respond to extracellular environmental changes, and causes the host infection. Two-component system (TCS) and second messenger (SM) are important regulation systems ubiquitous in APEC and play vital roles in regulating a variety of bacterial functions, such as biofilm formation, HO stress response, and virulence. Among them, BasS/BasR is a typical TCS, and c-di-GMP is a widely utilized intracellular SM. The metabolism of c-di-GMP is inversely controlled by diguanylate cyclase (DGC) and phosphodiesterase (PDE). However, the connection between BasS/BasR and c-di-GMP in regulating the biological functions of APEC has not yet been clarified. This study aims to investigate the cross-regulation between BasS/BasR and YfgF in biofilm formation, HO stress response, and APEC virulence, and to elucidate the underlying molecular mechanisms. In this study, we first demonstrated that BasS/BasR inhibits the transcription of yfgF (encoding a c-di-GMP phosphodiesterase YfgF) by directly binding to its promoter and resulted in increased intracellular c-di-GMP levels in response to extracellular signals. This, in turn, results in increased biofilm formation, promotes APEC adhesion, and reduces resistance to HO. Furthermore, BasS/BasR also directly facilitates biofilm formation, enhances APEC virulence, and increases sensitivity to HO by specifically binding to the promoters of csgD, ais, fepA, and yciFE, respectively. Taken together, this study suggests that the cross-regulation between BasS/BasR and c-di-GMP plays important roles in controlling biofilm formation, HO stress response, and APEC virulence, thereby providing valuable insights into bacterial pathogenicity.
禽致病性大肠杆菌（APEC）是一种广泛传播的细菌病原体，对全球家禽业构成重大威胁。通过研究调节APEC适应新环境及其生存的分子机制来控制APEC感染具有重要意义。APEC拥有一系列调节系统，以感知并快速适当地应对细胞外环境变化，并引发宿主感染。双组分系统（TCS）和第二信使（SM）是APEC中普遍存在的重要调节系统，在调节多种细菌功能（如生物膜形成、HO应激反应和毒力）中发挥着至关重要的作用。其中，BasS/BasR是典型的TCS，而环二鸟苷酸（c-di-GMP）是广泛使用的细胞内SM。c-di-GMP的代谢由二鸟苷酸环化酶（DGC）和磷酸二酯酶（PDE）反向控制。然而，BasS/BasR与c-di-GMP在调节APEC生物学功能方面的联系尚未阐明。本研究旨在探究BasS/BasR与YfgF在生物膜形成、HO应激反应和APEC毒力方面的交叉调节作用，并阐明其潜在的分子机制。在本研究中，我们首先证明BasS/BasR通过直接结合yfgF（编码c-di-GMP磷酸二酯酶YfgF）的启动子来抑制其转录，并导致细胞内c-di-GMP水平响应细胞外信号而升高。这反过来又导致生物膜形成增加，促进APEC黏附，并降低对HO的抗性。此外，BasS/BasR还分别通过特异性结合csgD、ais、fepA和yciFE的启动子，直接促进生物膜形成，增强APEC毒力，并增加对HO的敏感性。综上所述，本研究表明BasS/BasR与c-di-GMP之间的交叉调节在控制生物膜形成、HO应激反应和APEC毒力方面发挥着重要作用，从而为细菌致病性提供了有价值的见解。
