β-毒素促进金黄色葡萄球菌破坏血脑屏障的实验研究

王哲芬; 尹靓; 陈韬; 吴静琳; 郑颖

doi:10.16016/j.2097-0927.202308044

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β-毒素促进金黄色葡萄球菌破坏血脑屏障的实验研究

基础医学 | 更新时间：2026-01-09

- β-毒素促进金黄色葡萄球菌破坏血脑屏障的实验研究
- Experimental Research on β-toxin of Staphylococcus aureus promotes breaking the blood-brain barrier in mice
- 陆军军医大学学报 2024年46卷第6期页码：578-586
- 作者机构：
  
  1.650032 昆明，昆明医科大学第一附属医院神经内科
  2.650032 昆明，云南省神经系统疾病临床医学研究中心
- 作者简介：
  
  [郑颖，E-mail: zhengym@126.comZHENG Ying, E-mail: zhengym@126.com
- 基金信息：
  
  国家自然科学基金青年科学基金(82002196);云南省科技厅基础研究计划昆医联合专项－面上项目(202101AY070001-105);云南省神经系统疾病诊疗中心应用基础研究专项基金(ZX2019-03-05);云南省重大科技专项计划(202102AA100061)
- DOI：10.16016/j.2097-0927.202308044
  中图分类号： R322.81;R363.21;R378.11
- 收稿：2023-08-12，
  
  修回：2024-01-15，
  
  纸质出版：2024-03-30
- 稿件说明：
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王哲芬, 尹靓, 陈韬, 等. β-毒素促进金黄色葡萄球菌破坏血脑屏障的实验研究[J]. 陆军军医大学学报, 2024,46(6):578-586.

Zhefen WANG, Jing YIN, Tao CHEN, et al. Experimental Research on β-toxin of Staphylococcus aureus promotes breaking the blood-brain barrier in mice[J]. Journal of Army Medical University, 2024, 46(6): 578-586.
王哲芬, 尹靓, 陈韬, 等. β-毒素促进金黄色葡萄球菌破坏血脑屏障的实验研究[J]. 陆军军医大学学报, 2024,46(6):578-586. DOI： 10.16016/j.2097-0927.202308044.

Zhefen WANG, Jing YIN, Tao CHEN, et al. Experimental Research on β-toxin of Staphylococcus aureus promotes breaking the blood-brain barrier in mice[J]. Journal of Army Medical University, 2024, 46(6): 578-586. DOI： 10.16016/j.2097-0927.202308044.

摘要

目的

探讨β-毒素(Hlb)在金黄色葡萄球菌通过血脑屏障(blood-brain barrier

BBB)中的作用。

方法

通过血琼脂平板划线筛选金葡菌MW2的Hlb高产菌株，验证其对hCMEC/D3模拟BBB细胞模型通透性的影响。采用生物信息学分析筛选

hlb

基因完整的金葡菌菌株，利用同源重组的方法构建

hlb

敲除株，血琼脂平板法检测溶血活性改变。利用BBB细胞模型比较不同菌株对其通透性的影响，再将野生株与

hlb

敲除株经尾静脉注射构建小鼠血源性脑膜炎/脑微脓肿模型并比较感染72 h脑组织中菌载量。

结果

金葡菌MW2的Hlb高产菌株对BBB细胞模型破坏导致BBB细胞模型通透性增加的能力较野生株明显增强。NCTC8325-4、COL和RN4220菌株

hlb

基因无噬菌体插入。成功构建NCTC8325-4

Δhlb

株，血平板证实敲除株的β-溶血缺失。NCTC8325-4

Δhlb

株对BB

B模型细胞破坏导致BBB细胞模型通透性增加的作用较野生株下降，在小鼠血源性脑膜炎/脑微脓肿模型脑组织中菌载量也较野生株明显降低。

结论

β-毒素具有促进金葡菌破坏BBB的作用。

Abstract

Objective

To investigate the role of β-toxin (Hlb) in the penetration of

Staphylococcus aureus

(

S. aureus

) through blood-brain barrier (BBB).

Methods

The high Hlb-producing strain of

S. aureus

MW2 was screened by streaking on blood agar plate

and its effect on the permeability of hCMEC/D3 simulated BBB cell model was verified. Bioinformatics analysis was used to screen the strains with complete

hlb

gene

and then the

hlb

knockout strain was constructed with homologous recombination. The hemolytic activities of strains of interest were verified by streaking on blood agar plate. The permeability of different strains of

S. aureus

was compared in BBB cell model. A hematogenous meningitis/brain microabscess model was generated by injection of the wild-type or the

hlb

-deletion strain individually into CD1 mice through tail vain

and the bacterial load in the brain tissue was determined in 72 h after infection.

Results

The Hlb high-producing strain of MW2 (Hyper-β) led to increased permeability of the BBB model cells than the wild-type strain. The NCTC8325-4

COL

and RN4220 strains had intact

hlb

gene without phage insertion. The NCTC8325-4

Δhlb

strain was successfully constructed

and the lack of β-hemolysis of the mutant was verified by blood agar plate. A reduced permeability of NCTC8325-4

Δhlb

on the BBB cell model was observed in comparison to that of the wild-type strain. The bacterial load of NCTC8325-4

Δhlb

strain in the brain tissue of the mouse hematogenous meningitis/brain microabscess model was obviously lower than that of the wild-type

strain.

Conclusion

β-toxin from

S. aureus

promotes the bacteria destroying BBB.

关键词

Keywords

references

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