Impact of LuxS on virulence and pathogenicity in Klebsiella pneumoniae exhibiting varied mucoid phenotypes

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 bacteri