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利用群体感应抑制剂对抗生素耐药性的不断出现及其毒力减弱的研究:综述

Growing emergence of drug-resistant and attenuation of its virulence using quorum sensing inhibitors: A critical review.

作者信息

Bhardwaj Snigdha, Bhatia Sonam, Singh Shaminder, Franco Francisco

机构信息

Department of Pharmaceutical Science, SHALOM Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences (SHUATS), Naini, Prayagraj, India.

Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad - 121 001, Haryana, India.

出版信息

Iran J Basic Med Sci. 2021 Jun;24(6):699-719. doi: 10.22038/IJBMS.2021.49151.11254.

Abstract

A perilous increase in the number of bacterial infections has led to developing throngs of antibiotics for increasing the quality and expectancy of life. is becoming resistant to all known conventional antimicrobial agents thereby posing a deadly threat to the human population. Nowadays, targeting virulence traits of infectious agents is an alternative approach to antimicrobials that is gaining much popularity to fight antimicrobial resistance. Quorum sensing (QS) involves interspecies communication via a chemical signaling pathway. Under this mechanism, cells work in a concerted manner, communicate with each other with the help of signaling molecules called auto-inducers (AI). The virulence of these strains is driven by genes, whose expression is regulated by AI, which in turn acts as transcriptional activators. Moreover, the problem of antibiotic-resistance in case of infections caused by becomes more alarming among immune-compromised patients, where the infectious agents easily take over the cellular machinery of the host while hidden in the QS mediated biofilms. Inhibition of the QS circuit of by targeting various signaling pathways such as LasR, RhlR, Pqs, and QScR transcriptional proteins will help in blocking downstream signal transducers which could result in reducing the bacterial virulence. The anti-virulence agent does not pose an immediate selective pressure on growing bacterium and thus reduces the pathogenicity without harming the target species. Here, we review exclusively, the growing emergence of multi-drug resistant (MDR) and the critical literature survey of QS inhibitors with their potential application of blocking infections.

摘要

细菌感染数量的危险增加促使人们研发了大量抗生素以提高生活质量和延长寿命。然而,(某些细菌)正变得对所有已知的传统抗菌剂产生耐药性,从而对人类构成致命威胁。如今,针对病原体的毒力特性是一种对抗抗菌药物耐药性且越来越受欢迎的替代抗菌方法。群体感应(QS)涉及通过化学信号通路进行种间通讯。在这种机制下,细胞协同工作,借助称为自诱导物(AI)的信号分子相互通讯。这些菌株的毒力由基因驱动,其表达受AI调控,而AI又充当转录激活因子。此外,在免疫功能低下的患者中,由(某些细菌)引起的感染的抗生素耐药性问题变得更加令人担忧,在这些患者中,病原体隐藏在QS介导的生物膜中时很容易接管宿主的细胞机制。通过靶向LasR、RhlR、Pqs和QScR转录蛋白等各种信号通路来抑制(某些细菌)的QS回路,将有助于阻断下游信号转导器,从而降低细菌毒力。抗毒力剂不会对生长中的细菌立即施加选择压力,因此在不伤害目标物种的情况下降低了致病性。在此,我们专门综述多重耐药(MDR)(某些细菌)的日益出现以及QS抑制剂的关键文献调查及其在阻断(某些细菌)感染方面的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d822/8487598/3631b3f969b0/IJBMS-24-699-g001.jpg

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