关键词: K+ efflux NLRP3 PLO Trueperella pyogenes cholesterol-dependent cytolysin single-point mutation

Mesh : Animals Point Mutation Mice Hemolysin Proteins / metabolism genetics NLR Family, Pyrin Domain-Containing 3 Protein / metabolism genetics Bacterial Proteins / metabolism genetics Inflammation / metabolism genetics Potassium / metabolism Signal Transduction Bacterial Toxins / metabolism genetics Inflammasomes / metabolism Humans

来  源:   DOI:10.3390/ijms25126703   PDF(Pubmed)

Abstract:
Trueperella pyogenes is an important opportunistic pathogenic bacterium widely distributed in the environment. Pyolysin (PLO) is a primary virulence factor of T. pyogenes and capable of lysing many different cells. PLO is a member of the cholesterol-dependent cytolysin (CDC) family of which the primary structure only presents a low level of homology with other members from 31% to 45%. By deeply studying PLO, we can understand the overall pathogenic mechanism of CDC family proteins. This study established a mouse muscle tissue model infected with recombinant PLO (rPLO) and its single-point mutations, rPLO N139K and rPLO F240A, and explored its mechanism of causing inflammatory damage. The inflammatory injury abilities of rPLO N139K and rPLO F240A are significantly reduced compared to rPLO. This study elaborated on the inflammatory mechanism of PLO by examining its unit point mutations in detail. Our data also provide a theoretical basis and practical significance for future research on toxins and bacteria.
摘要:
化脓性梭菌是一种重要的机会致病菌,广泛分布于环境中。溶血素(PLO)是化脓性产热杆菌的主要毒力因子并且能够裂解许多不同的细胞。PLO是胆固醇依赖性细胞溶素(CDC)家族的成员,其一级结构仅与其他成员的同源性较低,为31%至45%。通过深入研究巴解组织,我们可以了解CDC家族蛋白的整体致病机制。本研究建立了感染重组PLO(rPLO)及其单点突变的小鼠肌肉组织模型,rPLON139K和rPLOF240A,探讨其引起炎症损伤的机制。与rPLO相比,rPLON139K和rPLOF240A的炎性损伤能力显著降低。本研究通过详细检查PLO的单位点突变,阐述了PLO的炎症机制。我们的数据也为今后毒素和细菌的研究提供了理论基础和现实意义。
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