The two-component system (TCS) helps bacteria sense and respond to environmental stimuli through histidine kinases and response regulators. TCSs are the largest family of multistep signal transduction processes, and they are involved in many important cellular processes such as antibiotic resistance, pathogenicity, quorum sensing, osmotic stress, and biofilms. Here, we perform the first comprehensive study to highlight the role of TCSs as potential drug targets against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli) pathogens through annotation, mapping, pangenomic status, gene orientation, and sequence variation analysis. The distribution of the TCSs is group specific with regard to Gram-positive and Gram-negative bacteria, except for KdpDE. The TCSs among ESKAPEE pathogens form closed pangenomes, except for Pseudomonas aeruginosa. Furthermore, their conserved nature due to closed pangenomes might make them good drug targets. Fitness score analysis suggests that any mutation in some TCSs such as BaeSR, ArcBA, EvgSA, and AtoSC, etc., might be lethal to the cell. Taken together, the results of this pangenomic assessment of TCSs reveal a range of strategies deployed by the ESKAPEE pathogens to manifest pathogenicity and antibiotic resistance. This study further suggests that the conserved features of TCSs might make them an attractive group of potential targets with which to address antibiotic resistance.

中文翻译：

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Pangenome Analytics将两组分系统揭示为ESKAPEE病原体中的保守靶标

两组分系统（TCS）通过组氨酸激酶和响应调节剂帮助细菌感应和响应环境刺激。TCS是最大的多步信号转导过程家族，它们参与许多重要的细胞过程，例如抗生素抗性，致病性，群体感应，渗透压和生物膜。在这里，我们进行了首次全面研究，以突出TCS作为潜在抗ESKAPEE的药物靶标的作用（粪肠球菌，金黄色葡萄球菌，肺炎克雷伯菌，鲍曼不动杆菌，铜绿假单胞菌，肠杆菌属和大肠杆菌）。病原体通过注释，作图，基因组状况，基因方向和序列变异分析。除KdpDE以外，TCS的分布对于革兰氏阳性和革兰氏阴性细菌是特定的。除铜绿假单胞菌外，ESKAPEE病原体中的TCS形成封闭的全基因组。此外，由于封闭的基因组，它们的保守性质可能使其成为良好的药物靶标。适应性评分分析表明，某些TCS中的任何突变（如BaeSR，ArcBA，EvgSA和AtoSC等）都可能对细胞致命。综上所述，TCS的全基因组学评估结果揭示了ESKAPEE病原体采用的一系列策略来表现出致病性和抗生素抗性。这项研究进一步表明，TCS的保守特征可能使它们成为解决抗生素耐药性的一组有吸引力的潜在靶标。