School of Life Science and Engineering, Foshan University, Foshan, Guangdong, China; Foshan University Veterinary Teaching Hospital, Foshan University, Foshan, Guangdong, China.
School of Life Science and Engineering, Foshan University, Foshan, Guangdong, China.
Int Immunopharmacol. 2024 Oct 25;140:112829. doi: 10.1016/j.intimp.2024.112829. Epub 2024 Jul 30.
Streptococcus equi subsp. zooepidemicus (S. zooepidemicus, SEZ) is an essential zoonotic bacterial pathogen that can cause various inflammation, such as meningitis, endocarditis, and pneumonia. UDP-glucose dehydrogenase (hasB) is indispensable in synthesizing SEZ virulence factor hyaluronan capsules. Our study investigated the infection of hasB on mice response to SEZ by employing a constructed capsule-deficient mutant strain designated as the ΔhasB strain. This deficiency was associated with a reduced SEZ bacterial load in the mice's blood and peritoneal lavage fluid (PLF) post-infection. Besides, the ΔhasB SEZ strain exhibited a higher propensity for neutrophil infiltration and release of cell-free DNA (cfDNA) in vivo compared to the wild-type (WT) SEZ strain. In vitro experiments further revealed that ΔhasB SEZ more effectively induced the formation of neutrophil extracellular traps (NETs) containing histone 3 (H3), neutrophil elastase (NE), and DNA, than its WT counterpart. Moreover, the release of NETs was determined to be gasdermin D (GSDMD)-dependent during the infection process. Taken together, these findings underscore that the deficiency of the hasB gene in SEZ leads to enhanced GSDMD-dependent NET release from neutrophils, thereby reducing SEZ's capacity to resist NETs-mediated eradication during infection. Our finding paves the way for the development of innovative therapeutic strategies against SEZ.
马链球菌兽疫亚种（Streptococcus equi subsp. zooepidemicus，S. zooepidemicus，SEZ）是一种重要的人畜共患病细菌病原体，可引起各种炎症，如脑膜炎、心内膜炎和肺炎。UDP-葡萄糖脱氢酶（hasB）在合成 SEZ 毒力因子透明质酸胶囊中不可或缺。我们的研究通过构建缺乏荚膜的突变株，即 ΔhasB 株，研究了 hasB 对 SEZ 感染小鼠的影响。这种缺陷与感染后小鼠血液和腹腔灌洗液（peritoneal lavage fluid，PLF）中 SEZ 细菌载量减少有关。此外，与野生型（WT）SEZ 菌株相比，ΔhasB SEZ 菌株在体内更容易引起中性粒细胞浸润和细胞游离 DNA（cell-free DNA，cfDNA）的释放。体外实验进一步表明，与 WT SEZ 相比，ΔhasB SEZ 更有效地诱导含有组蛋白 3（histone 3，H3）、中性粒细胞弹性蛋白酶（neutrophil elastase，NE）和 DNA 的中性粒细胞细胞外陷阱（neutrophil extracellular traps，NETs）的形成。此外，在感染过程中，NETs 的释放被确定为依赖于 GSDMD。综上所述，这些发现强调了 SEZ 中 hasB 基因的缺失导致 GSDMD 依赖性 NET 从中性粒细胞中释放增强，从而降低 SEZ 在感染过程中抵抗 NETs 介导的清除的能力。我们的发现为开发针对 SEZ 的创新治疗策略铺平了道路。
