链球菌A组的自然变异碳水化合物生物合成基因影响宿主-病原体相互作用
Kim Schipper1, Sara M Tamminga1, Nicholas Murner2
1Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
bioRxiv : the preprint server for biology
|November 22, 2024
概括
在Streptococcus pyogenes gacH中罕见的突变破坏了A组的碳水化合物装饰,影响了病原性和诊断测试. 这项研究分析了S. pyogenes中Gac基因变异和GacH功能丧失.
科学领域:
- 微生物学 微生物学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 链球菌 pyogenes (S. pyogenes) 导致全球显著的死亡率.
- A组碳水化合物 (GAC) 细胞壁组成部分对于S. pyogenes的致病性和诊断至关重要.
- GAC生物合成涉及 gacA-L 基因集群, gacH-L 负责 N-乙烯基葡萄糖胺 (GlcNAc) 和甘酸 (GroP) 装饰.
研究的目的:
- 在全球S. pyogenes种群中调查 gacA-L基因集群的遗传变异.
- 确定GacH中失活突变对GAC生物合成和S. pyogenes特征的功能后果.
主要方法:
- 对2021个S. pyogenes基因组序列的基因组分析,以确定 gacA-L 集群中的变异.
- 在S. pyogenes gacH缺乏菌株中,基于等离子体的三种 gacH变体的表达.
- 细胞壁分析以评估GAC GroP水平,对IIA组分泌的脂酶的耐药性,以及对毒性的敏感性.
主要成果:
- 只有1.3%的S. pyogenes分离物 (26/2,021) 在 gac 基因中具有过早停止密码子;其中46%在 gacH. 中具有突变.
- 研究的 gacH 变体导致功能丧失,显著减少了 GAC GroP.
- 失去了GacH功能赋予了对IIA组分泌的脂酶的完全耐药性,并增加了对毒性的敏感性.
结论:
- 在 gacH 中罕见的失活突变显著影响了 GAC 结构和 S. pyogenes 主体相互作用.
- GacH功能丧失影响病原性,并可能改变诊断测试的性能.
- 这项研究提供了 gac 集群变异和 gacH 突变的功能影响的全面概述.
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