Lella Muralikrishna, Tal-Gan Yftah
Department of Chemistry, University of Nevada, Reno, 1664 North Virginia Street, Reno, NV 89557 (USA).
Pept Sci (Hoboken). 2021 Jul;113(4). doi: 10.1002/pep2.24222. Epub 2021 Feb 4.
is an opportunistic respiratory human pathogen that poses a continuing threat to human health. Natural competence for genetic transformation in 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 , 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. 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 (dnCSP) scaffolds. We also discuss recent reports on antibiotics that can block CSP export by disturbing the proton motive force (PMF) across the membrane and various ways to control the pneumococcal pathogenicity by activating the counter signaling circuit and targeting the pneumococcal proteome.
是一种机会性人类呼吸道病原体，对人类健康构成持续威胁。其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微生物耐药基因是其最具特征的特性。在其中，感受态与毒力因子的产生一样，受一种称为感受态调节子的细胞密度通讯机制控制。在本综述中，我们介绍了通过靶向非必需感受态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开发的最新进展。我们主要关注通过引入有前景的显性负性感受态刺激肽（dnCSP）支架竞争性拦截感受态调节子信号相关的新进展。我们还讨论了关于可通过干扰跨膜质子动力势（PMF）来阻断CSP输出的抗生素的最新报道，以及通过激活反向信号回路和靶向肺炎链球菌蛋白质组来控制肺炎链球菌致病性的各种方法。
