TCS01 Two-Component System Influenced the Virulence of Streptococcus pneumoniae by Regulating PcpA
TCS01 Two-Component System Influenced the Virulence of Streptococcus pneumoniae by Regulating PcpA
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DOI：
10.1128/iai.00100-23
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发表时间：
2023-04
影响因子：
3.1
通讯作者：
Wei-Li Yu;Jin-Ge Pan;Ru-Xue Qin;Zhong-Hua Lu;X. Bai;Yun Sun
中科院分区：
文献类型：
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作者：
Wei-Li Yu;Jin-Ge Pan;Ru-Xue Qin;Zhong-Hua Lu;X. Bai;Yun Sun
肺炎链球菌依赖于双组分系统（TCS）来调节致病性、渗透压、趋化性和能量代谢过程。S. pneumoniae由HK 01（组氨酸激酶）和RR 01（反应调节因子）组成。摘要肺炎链球菌依靠双组分系统（TCS）调节致病性、渗透压、趋化性和能量代谢过程。S. pneumoniae由HK 01（组氨酸激酶）和RR 01（反应调节因子）组成。先前的研究已经报道rr 01突变体在大鼠肺炎、菌血症、鼻咽模型和感染性心内膜炎中降低了肺炎球菌的毒力。然而，TCS 01（HK/RR 01）调节肺炎球菌毒力的机制尚不清楚。在此，构建了肺炎球菌突变株Δ rr 01、Δ hk 01和Δ rr 0101，并比较了细菌对A549细胞的粘附和侵袭。在D39野生型和Δ rr 01菌株中进行RNA测序，并分析转录谱变化。利用实时荧光定量PCR（qRT-PCR）技术筛选Δ rr 01菌株毒力差异表达基因。我们的研究结果表明，肺炎球菌突变株表现出减弱粘附和侵袭A549细胞和差异转录谱。qRT-PCR鉴定结果显示，筛选出的差异毒力基因表达下调。在Δ rr 01株毒力基因中，胆碱结合蛋白pcpA的表达下调最为明显。Δ rr 01株rr 01互补和pcpA过表达部分恢复了肺炎球菌的粘附和侵袭能力，rr 01互补使pcpA表达上调。这些结果表明，rr 01影响肺炎球菌的毒力通过调节pcpA。
Streptococcus pneumoniae relies on two-component systems (TCSs) to regulate the processes of pathogenicity, osmotic pressure, chemotaxis, and energy metabolism. The TCS01 system of S. pneumoniae is composed of HK01 (histidine kinase) and RR01 (response regulator). ABSTRACT Streptococcus pneumoniae relies on two-component systems (TCSs) to regulate the processes of pathogenicity, osmotic pressure, chemotaxis, and energy metabolism. The TCS01 system of S. pneumoniae is composed of HK01 (histidine kinase) and RR01 (response regulator). Previous studies have reported that an rr01 mutant reduced the pneumococcal virulence in rat pneumonia, bacteremia, a nasopharyngeal model, and infective endocarditis. However, the mechanism of TCS01 (HK/RR01) regulating pneumococcal virulence remains unclear. Here, pneumococcal mutant strains Δrr01, Δhk01, and Δrr0101 were constructed, and bacterial adhesion and invasion to A549 cells were compared. RNA sequencing was performed in D39 wild-type and Δrr01 strains, and transcript profile changes were analyzed. Differentially expressed virulence genes in the Δrr01 strain were screened out and identified by quantitative real-time PCR (qRT-PCR). Our results showed that pneumococcal mutant strains exhibited attenuated adhesion and invasion to A549 cells and differential transcript profiles. Results of qRT-PCR identification showed that the differential virulence genes screened out were downregulated. Among those changed virulence genes in the Δrr01 strain, the downregulated expression level of choline binding protein pcpA was the most obvious. Complementation of rr01 and overexpression of pcpA in the Δrr01 strain partially restored both pneumococcal adhesion and invasion, and rr01 complementation made the expression of pcpA upregulated. These findings revealed that rr01 influenced pneumococcal virulence by regulating pcpA.