香白藻 (Candida albicans) 激活金黄色葡萄球菌 (Staphylococcus aureus) 毒性调节系统,以驱动毒素介导的人类细胞死亡
Kara R Eichelberger1, Nicholas A Podar1, Jia A Mei2
1Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA.
bioRxiv : the preprint server for biology
|November 19, 2025
概括
与黄金葡萄球菌和白菌的同时感染会使疾病恶化. 虫 Candida albicans 激活了一个通常无毒的金黄色菌株,通过SaeRS系统和PVL毒素导致强大的人类选择性细胞死亡.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 同时感染金黄色葡萄球菌 (S. aureus) 和白菌 (C. albicans) 会导致比单次感染更严重的疾病.
- 这种严重程度的增加背后的机制尚不清楚.
- 黄金菌的毒性受到Agr和SaeRS等系统的严格监管.
研究的目的:
- 研究C. albicans相互作用如何影响S. aureus对宿主免疫细胞的毒性.
- 为了确定特定的S. aureus毒性因子,负责在同时感染期间增强细胞毒性.
- 为了确定这些相互作用和结果是否在不同的宿主细胞和微生物菌株中保持.
主要方法:
- 在S. aureus和C. albicans与小鼠和人类单细胞的共同培养中.
- 使用的S. aureus突变,包括一个Agr删除突变 (Δagr).
- 使用报告菌株和组合突变来分析监管系统激活 (Agr,SaeRS).
- 量化了细胞毒性和确定了关键毒素,如溶性模块,γ-hemolysin和Panton-Valentine Leukocidin (PVL).
主要成果:
- C. albicans通过Agr系统增强S. aureus对小鼠单细胞的细胞毒性,涉及溶性模块和γ-hemolysin.
- 意想不到的是,C. albicans诱导了S. aureus Δagr突变体对人类单细胞的强烈细胞毒性,这种表型在小鼠细胞中没有观察到.
- 这种人体特异性细胞毒性是由SaeRS调节系统及其毒素PVL.调节的.
- 这些细胞毒性相互作用与S. aureus和C. albicans的临床分离物观察到,表明广泛的保存.
结论:
- C. albicans激活了S. aureus中的SaeRS病毒性调节系统,导致人类有力的选择性细胞死亡.
- 这种激活甚至发生在缺乏Agr系统的S. aureus菌株中,这些菌株通常是无毒的.
- 这些发现揭示了S. aureus介导的免疫逃避和共感染期间的发病机制,这对人类健康有影响.
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