PDF(Pubmed)
Abstract：
UNASSIGNED: Brucellosis, a significant zoonotic disease, not only impacts animal health but also profoundly influences the host immune responses through gut microbiome. Our research focuses on whole genome sequencing and comparative genomic analysis of these Brucella strains to understand the mechanisms of their virulence changes that may deepen our comprehension of the host immune dysregulation.
UNASSIGNED: The Brucella melitensis strain CMCC55210 and its naturally attenuated variant CMCC55210a were used as models. Biochemical identification tests and in vivo experiments in mice verified the characteristics of the strain. To understand the mechanism of attenuation, we then performed de novo sequencing of these two strains.
UNASSIGNED: We discovered notable genomic differences between the two strains, with a key single nucleotide polymorphism (SNP) mutation in the manB gene potentially altering lipopolysaccharide (LPS) structure and influencing host immunity to the pathogen. This mutation might contribute to the attenuated strain\'s altered impact on the host\'s macrophage immune response, overing insights into the mechanisms of immune dysregulation linked to intracellular survival. Furthermore, we explore that manipulating the Type I restriction-modification system in Brucella can significantly impact its genome stability with the DNA damage response, consequently affecting the host\'s immune system.
UNASSIGNED: This study not only contributes to understanding the complex relationship between pathogens, and the immune system but also opens avenues for innovative therapeutic interventions in inflammatory diseases driven by microbial and immune dysregulation.
UNASSIGNED: The Brucella melitensis strain CMCC55210 and its naturally attenuated variant CMCC55210a were used as models. Biochemical identification tests and in vivo experiments in mice verified the characteristics of the strain. To understand the mechanism of attenuation, we then performed de novo sequencing of these two strains.
UNASSIGNED: We discovered notable genomic differences between the two strains, with a key single nucleotide polymorphism (SNP) mutation in the manB gene potentially altering lipopolysaccharide (LPS) structure and influencing host immunity to the pathogen. This mutation might contribute to the attenuated strain\'s altered impact on the host\'s macrophage immune response, overing insights into the mechanisms of immune dysregulation linked to intracellular survival. Furthermore, we explore that manipulating the Type I restriction-modification system in Brucella can significantly impact its genome stability with the DNA damage response, consequently affecting the host\'s immune system.
UNASSIGNED: This study not only contributes to understanding the complex relationship between pathogens, and the immune system but also opens avenues for innovative therapeutic interventions in inflammatory diseases driven by microbial and immune dysregulation.
摘要：
■布鲁氏菌病，一种重要的人畜共患疾病，不仅影响动物健康，而且还通过肠道微生物组深刻影响宿主的免疫反应。我们的研究重点是对这些布鲁氏菌菌株进行全基因组测序和比较基因组分析，以了解其毒力变化的机制，这可能会加深我们对宿主免疫失调的理解。
■使用布鲁氏菌菌株CMCC55210及其天然减毒变体CMCC55210a作为模型。生化鉴定试验和小鼠体内实验验证了该菌株的特性。要了解衰减的机制，然后我们对这两个菌株进行了从头测序。
■我们发现了两个菌株之间的显著基因组差异，在manB基因中具有关键的单核苷酸多态性（SNP）突变，可能会改变脂多糖（LPS）结构并影响宿主对病原体的免疫力。这种突变可能有助于减毒株改变对宿主巨噬细胞免疫反应的影响，深入了解与细胞内生存相关的免疫失调机制。此外，我们发现，在布鲁氏菌中操纵I型限制性修饰系统可以显着影响其DNA损伤反应的基因组稳定性，从而影响宿主的免疫系统。
■这项研究不仅有助于理解病原体之间的复杂关系，和免疫系统，但也为微生物和免疫失调驱动的炎症性疾病的创新治疗干预开辟了途径。
■使用布鲁氏菌菌株CMCC55210及其天然减毒变体CMCC55210a作为模型。生化鉴定试验和小鼠体内实验验证了该菌株的特性。要了解衰减的机制，然后我们对这两个菌株进行了从头测序。
■我们发现了两个菌株之间的显著基因组差异，在manB基因中具有关键的单核苷酸多态性（SNP）突变，可能会改变脂多糖（LPS）结构并影响宿主对病原体的免疫力。这种突变可能有助于减毒株改变对宿主巨噬细胞免疫反应的影响，深入了解与细胞内生存相关的免疫失调机制。此外，我们发现，在布鲁氏菌中操纵I型限制性修饰系统可以显着影响其DNA损伤反应的基因组稳定性，从而影响宿主的免疫系统。
■这项研究不仅有助于理解病原体之间的复杂关系，和免疫系统，但也为微生物和免疫失调驱动的炎症性疾病的创新治疗干预开辟了途径。
