Tang Miran, Zhao Deyi, Zhang Ying, Qian Changrui, Chen Huale, Chen Lijiang, Ye Jianzhong, Zhou Tieli
Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Infect Immun. 2024 Mar 12;92(3):e0001224. doi: 10.1128/iai.00012-24. Epub 2024 Feb 15.
How the LuxS/AI-2 quorum sensing (QS) system influences the pathogenicity of is complicated by the heterogeneity of the bacterial mucoid phenotypes. This study aims to explore the LuxS-mediated regulation of the pathogenicity of with diverse mucoid phenotypes, including hypermucoid, regular-mucoid, and nonmucoid. The wild-type, knockout, and complemented strains of three clinical isolates with distinct mucoid phenotypes were constructed. The results revealed the downregulation of virulence genes of regular-mucoid, and nonmucoid but not hypermucoid strains. The deletion of reduced the pathogenicity of the regular-mucoid, and nonmucoid strains in mice; while in hypermucoid strain, knockout reduced virulence in late growth but enhanced virulence in the early growth phase. Furthermore, the absence of led the regular-mucoid and nonmucoid strains to be more sensitive to the host cell defense, and less biofilm-productive than the wild-type at both the low and high-density growth state. Nevertheless, knockout enhanced the resistances to adhesion and phagocytosis by macrophage as well as serum-killing, of hypermucoid at its early low-density growth state, while it was opposite to those in its late high-density growth phase. Collectively, our results suggested that LuxS plays a crucial role in the pathogenicity of , and it is highly relevant to the mucoid phenotypes and growth phases of the strains. LuxS probably depresses the capsule in the early low-density phase and promotes the capsule, biofilm, and pathogenicity during the late high-density phase, but inhibits lipopolysaccharide throughout the growth phase, in .IMPORTANCECharacterizing the regulation of physiological functions by the LuxS/AI-2 quorum sensing (QS) system in strains will improve our understanding of this important pathogen. The genetic heterogeneity of isolates complicates our understanding of its pathogenicity, and the association of LuxS with bacterial pathogenicity has remained poorly addressed in . Our results demonstrated strain and growth phase-dependent variation in the contributions of LuxS to the virulence and pathogenicity of . Our findings provide new insights into the important contribution of the LuxS/AI-2 QS system to the networks that regulate the pathogenicity of . Our study will facilitate our understanding of the regulatory mechanisms of LuxS/AI-2 QS on the pathogenicity of under the background of their genetic heterogeneity and help develop new strategies for diminished bacterial virulence within the clinical population.
LuxS/AI-2群体感应（QS）系统如何影响[细菌名称]的致病性，因细菌黏液样表型的异质性而变得复杂。本研究旨在探索LuxS介导的对具有不同黏液样表型（包括高黏液样、正常黏液样和非黏液样）的[细菌名称]致病性的调控。构建了具有不同黏液样表型的三株[细菌名称]临床分离株的野生型、LuxS基因敲除型和互补菌株。结果显示，正常黏液样和非黏液样菌株（而非高黏液样菌株）的毒力基因表达下调。LuxS基因的缺失降低了正常黏液样和非黏液样菌株在小鼠体内的致病性；而在高黏液样菌株中，LuxS基因敲除在生长后期降低了毒力，但在生长早期增强了毒力。此外，LuxS基因的缺失使正常黏液样和非黏液样菌株对宿主细胞防御更敏感，并且在低密度和高密度生长状态下比野生型菌株产生的生物膜更少。然而，在高黏液样[细菌名称]的早期低密度生长状态下，LuxS基因敲除增强了其对巨噬细胞黏附、吞噬以及血清杀伤的抗性，而在后期高密度生长阶段则相反。总体而言，我们的结果表明LuxS在[细菌名称]的致病性中起关键作用，并且与菌株的黏液样表型和生长阶段高度相关。在[细菌名称]中，LuxS可能在早期低密度阶段抑制荚膜形成，在后期高密度阶段促进荚膜、生物膜形成和致病性，但在整个生长阶段抑制脂多糖的产生。
表征LuxS/AI-2群体感应（QS）系统对[细菌名称]菌株生理功能的调控，将增进我们对这种重要病原体的理解。[细菌名称]分离株的遗传异质性使我们对其致病性的理解变得复杂，并且LuxS与细菌致病性的关联在[细菌名称]中仍未得到充分研究。我们的结果表明，LuxS对[细菌名称]毒力和致病性的贡献存在菌株和生长阶段依赖性差异。我们的发现为LuxS/AI-2 QS系统对调控[细菌名称]致病性的网络的重要贡献提供了新见解。我们的研究将有助于在其遗传异质性背景下理解LuxS/AI-2 QS对[细菌名称]致病性 的调控机制，并有助于制定新策略以降低临床[细菌名称]群体内细菌的毒力。
