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群体感应调节因子SarA靶向化合物2-[(甲氨基)甲基]苯酚可抑制生物膜形成并下调毒力基因。

Quorum Regulator SarA Targeted Compound, 2-[(Methylamino)methyl]phenol Inhibits Biofilm and Down-Regulates Virulence Genes.

作者信息

Balamurugan P, Praveen Krishna V, Bharath D, Lavanya Raajaraam, Vairaprakash Pothiappan, Adline Princy S

机构信息

Quorum Sensing Laboratory, Centre for Research on Infectious Diseases, School of Chemical and Biotechnology, SASTRA UniversityThanjavur, India.

Department of Chemistry, School of Chemical and Biotechnology, SASTRA UniversityThanjavur, India.

出版信息

Front Microbiol. 2017 Jul 11;8:1290. doi: 10.3389/fmicb.2017.01290. eCollection 2017.

Abstract

is a widely acknowledged Gram-positive pathogen for forming biofilm and virulence gene expressions by quorum sensing (QS), a cell to cell communication process. The quorum regulator SarA of up-regulates the expression of many virulence factors including biofilm formation to mediate pathogenesis and evasion of the host immune system in the late phases of growth. Thus, inhibiting the production or blocking SarA protein might influence the down-regulation of biofilm and virulence factors. In this context, here we have synthesized 2-[(Methylamino)methyl]phenol, which was specifically targeted toward the quorum regulator SarA through approach in our previous study. The molecule has been evaluated to validate its antibiofilm activity against clinical strains. In addition, antivirulence properties of the inhibitor were confirmed with the observation of a significant reduction in the expression of representative virulence genes like and that are governed under QS. Interestingly, the SarA targeted inhibitor showed negligible antimicrobial activity and markedly reduced the minimum inhibitory concentration of conventional antibiotics when used in combination making it a more attractive lead for further clinical tests.

摘要

是一种广泛认可的革兰氏阳性病原体,通过群体感应(QS)形成生物膜并进行毒力基因表达,群体感应是一种细胞间通讯过程。在生长后期,群体感应调节因子SarA上调包括生物膜形成在内的许多毒力因子的表达,以介导发病机制并逃避宿主免疫系统。因此,抑制SarA蛋白的产生或阻断其功能可能会影响生物膜和毒力因子的下调。在此背景下,我们在此合成了2-[(甲氨基)甲基]苯酚,在我们之前的研究中,它通过特定方法靶向群体感应调节因子SarA。该分子已被评估以验证其对临床菌株的抗生物膜活性。此外,通过观察受QS调控的代表性毒力基因如[具体基因1]和[具体基因2]表达的显著降低,证实了该抑制剂的抗毒力特性。有趣的是,靶向SarA的抑制剂显示出可忽略不计的抗菌活性,并且在与传统抗生素联合使用时显著降低了其最小抑菌浓度,使其成为更具吸引力的进一步临床试验先导物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afeb/5504099/d7cc19ae4e57/fmicb-08-01290-g001.jpg

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