黄金葡萄球菌 (Staphylococcus aureus) 全球调节剂CodY中的突变使得一种跨物种氧活性抗菌剂具有耐受性
Anthony M Martini1, Sara A Alexander1, Anupama Khare1
1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
bioRxiv : the preprint server for biology
|July 23, 2024
概括
黄金葡萄球菌通过改变其全球调节剂CodY.适应了抗微生物皮亚氨酸. 这种适应涉及抑制新陈代谢和过度表达酶,增强共感染中的细菌存活率.
科学领域:
- 微生物学 微生物学
- 细菌病原体的产生
- 分子生物学分子生物学
背景情况:
- 细菌经常在多种群体中共存,导致复杂的相互作用.
- 相互作用可以影响细菌的健康状况,但对抗对抗的分子适应性尚未得到充分探索.
- 黄金葡萄球菌和 Pseudomonas aeruginosa 经常同时感染,而P. aeruginosa 产生抗菌素皮奥.
研究的目的:
- 描述Staphylococcus aureus的分子适应性,以适应pyocyanin的情况.
- 为了确定赋予皮约素耐受性的遗传突变.
- 阐明S. aureus在抗击pyocyanin时使用的防御机制.
主要方法:
- 在pyocyanin的存在下S. aureus的实验进化.
- 在全球转录调节器CodY.中发现突变.
- 野生型和CodY突变菌株的转录概况,在暴露于pyocyanin时.
- 评估催化酶活性及其在皮奥素耐受性中的作用.
主要成果:
- 在CodY中发生的突变赋予了显著的皮约素耐受性和增强的S. aureus存活率.
- 该CodY突变体表现出双重防御:抑制核心新陈代谢和高调氧化应激反应.
- 仅仅抑制新陈代谢就提供了对皮约亚的实质性保护.
- 过度表达catalase对于CodY突变体的皮亚氨酸耐受性至关重要,并且足以赋予对野生类型菌株的耐受性.
结论:
- CodY是S. aureus适应皮亚氨酸诱导的压力的关键调节剂.
- 适应涉及协调的转录反应,包括代谢抑制和增强的氧化应激防御.
- catalase过度表达是皮约西亚尼耐受性的关键机制.
- 了解这些适应提供了机制性的洞察力,可以了解细菌间对抗期间细菌的生存情况.
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