Development of Streptococcus pneumoniae Pan-Group Quorum-Sensing Modulators
Development of Streptococcus pneumoniae Pan-Group Quorum-Sensing Modulators
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DOI：
10.1002/cbic.201900365
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发表时间：
2020-02-03
期刊：
影响因子：
3.2
通讯作者：
Tal-Gan, Yftah
中科院分区：
文献类型：
--
作者：
Koirala, Bimal;Tal-Gan, Yftah
耐多药病原体的迅速增加是一个重大的健康问题，可能会使人类回到前抗生素时代。肺炎链球菌是一种高度重组的机会致病菌，可引起多种致命疾病，并迅速对目前的抗生素治疗产生耐药性。S.肺炎克雷伯氏菌的致病性依赖于称为感受态调节子的细胞密度通讯机制或群体感应（QS）。在这项工作中，我们着手设计能够影响S.肺炎。通过系统分析和合理设计，我们能够构建基于肽的泛基团QS激活剂和抑制剂，其活性在纳摩尔范围内。这些新的类似物是开发抗S.肺炎感染。
The rapid increase in multidrug-resistant pathogens is a major health concern that could bring mankind back to the pre-antibiotic era. Streptococcus pneumoniae is a highly recombinogenic opportunistic pathogen that causes a variety of deadly diseases and rapidly develops resistance to current antibiotic treatments. S. pneumoniae pathogenicity is dependent on a cell-density communication mechanism, or quorum sensing (QS), termed the competence regulon. In this work, we set out to design signal-based QS modulators capable of affecting the two specificity groups found in S. pneumoniae. Through systematic analysis and rational design, we were able to construct peptide-based pan-group QS activators and inhibitors with activities in the nanomolar range. These novel analogues are privileged scaffolds for the development of anti-virulence therapeutics against S. pneumoniae infections.