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Strategies to attenuate the competence regulon in Streptococcus pneumoniae
Peptide Science ( IF 1.5 ) Pub Date : 2021-02-04 , DOI: 10.1002/pep2.24222
Muralikrishna Lella 1 , Yftah Tal-Gan 1
Affiliation  

Streptococcus pneumoniae is an opportunistic respiratory human pathogen that poses a continuing threat to human health. Natural competence for genetic transformation in S. pneumoniae plays an important role in aiding pathogenicity and it is the best-characterized feature to acquire antimicrobial resistance genes by a frequent process of recombination. In S. pneumoniae, competence, along with virulence factor production, is controlled by a cell-density communication mechanism termed the competence regulon. In this review, we present the recent advances in the development of alternative methods to attenuate the pathogenicity of S. pneumoniae by targeting the various stages of the non-essential competence regulon communication system. We mainly focus on new developments related to competitively intercepting the competence regulon signaling through the introduction of promising dominant-negative Competence Stimulating Peptide (CSP) scaffolds. We also discuss recent reports on antibiotics that can block CSP export by disturbing the proton motive force across the membrane and various ways to control the pneumococcal pathogenicity by activating the counter signaling circuit and targeting the pneumococcal proteome.

中文翻译:

减弱肺炎链球菌能力调节的策略

肺炎链球菌是一种机会性呼吸道人类病原体,对人类健康构成持续威胁。肺炎链球菌遗传转化的自然能力在辅助致病性方面发挥着重要作用,并且通过频繁的重组过程获得抗菌素耐药性基因是最典型的特征。在肺炎链球菌中,能力以及毒力因子的产生是由称为能力调节子的细胞密度通讯机制控制的。在这篇综述中,我们介绍了通过针对非必需能力调节子通讯系统的各个阶段来减弱肺炎链球菌致病性的替代方法的开发的最新进展。我们主要关注通过引入有前景的显性失活能力刺激肽(CSP)支架来竞争性拦截能力调节子信号相关的新进展。我们还讨论了最近关于抗生素的报道,这些抗生素可以通过干扰跨膜质子动力来阻止 CSP 输出,以及通过激活反信号电路和靶向肺炎球菌蛋白质组来控制肺炎球菌致病性的各种方法。
更新日期:2021-02-04
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