a Clinical Microbiology, Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
Virulence. 2019 Dec;10(1):502-510. doi: 10.1080/21505594.2019.1620062.
and are newly identified species of the -related complex. as occurring globally and showing significant prevalence and comparable infection and morbidity rates compared to , is becoming clinically important. Whole genome sequencing has revealed the presence of several virulence genes but the molecular mechanisms of infection and virulence are largely unknown. Here, we studied the effect of a previously characterized clinical isolate on human cells . The clinical isolate, together with the type strain MSHR1132T and the type strain FSA084T, had a cytotoxic effect on the cells, which showed necrotic cell death after a few hours of treatment. The protein causing the cytotoxic effect was purified and identified by mass spectrometry as alpha-hemolysin, Hla, which is awell-known pore-forming toxin in . The cytotoxic effect could be blocked with an antibody against Hla. showed 12-15 fold higher expression levels of at the RNA level and 4-6 fold higher expression levels at the protein level compared to . The higher expression levels of were supported by higher RNA levels of the regulatory factors and . Also, the RNAIII component of the accessory gene regulator (agr) quorum sensing system was 8,000-10,000 fold higher in the isolates compared to . This is the first study on the effect of on ahuman cell line and strengthens the idea of significant virulence of .
和 是新鉴定的 -相关复合体物种。 在全球范围内发生,其流行率和感染率与 相当,发病率也相当高,因此变得具有临床重要性。全基因组测序揭示了存在几种毒力基因,但 感染和毒力的分子机制在很大程度上尚不清楚。在这里,我们研究了先前表征的临床 分离株对人类细胞的影响。该临床分离株与 型菌株 MSHR1132T 和 型菌株 FSA084T 一起对细胞具有细胞毒性作用,在处理数小时后显示出坏死性细胞死亡。通过质谱法将引起细胞毒性作用的蛋白质鉴定为 alpha-hemolysin,Hla,这是 中一种众所周知的形成孔毒素。用针对 Hla 的抗体可以阻断细胞毒性作用。与 相比, 在 RNA 水平上表达水平高 12-15 倍,在蛋白质水平上高 4-6 倍。更高的 表达水平得到了调节因子 和 的更高 RNA 水平的支持。此外,辅助基因调节(agr)群体感应系统的 RNAIII 成分在 分离株中比 高 8000-10000 倍。这是首次研究 对人细胞系的影响,并加强了 的高毒力的想法。