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塞克硝唑是一种有前景的咪唑类毒力减轻剂。

Secnidazole Is a Promising Imidazole Mitigator of Virulence.

作者信息

Khayyat Ahdab N, Abbas Hisham A, Khayat Maan T, Shaldam Moataz A, Askoura Momen, Asfour Hani Z, Khafagy El-Sayed, Abu Lila Amr S, Allam Ahmed N, Hegazy Wael A H

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.

出版信息

Microorganisms. 2021 Nov 11;9(11):2333. doi: 10.3390/microorganisms9112333.

Abstract

is an opportunistic pathogen that causes diverse nosocomial infections. has developed considerable resistance to different antibiotics and is equipped with an armory of virulence factors. These virulence factors are regulated in by an intercellular communication system termed quorum sensing (QS). Targeting bacterial virulence and QS is an interesting approach to mitigating bacterial pathogenesis and overcoming the development of resistance to antimicrobials. In this study, we aimed to evaluate the anti-virulence activities of secnidazole on a clinical isolate of . The effects of secnidazole at sub-inhibitory concentrations (sub-MICs) on virulence factors, swarming motility, biofilm formation, proteases, hemolysin activity, and prodigiosin production were evaluated in vitro. Secnidazole's protective activity against pathogenesis was assessed in vivo in mice. Furthermore, a molecular docking study was conducted to evaluate the binding ability of secnidazole to the SmaR QS receptor. Our findings showed that secnidazole at sub-MICs significantly reduced virulence factor production in vitro and diminished its pathogenesis in mice. The docking study revealed a great ability of secnidazole to competitively hinder the binding of the autoinducer to the SmaR QS receptor. In conclusion, secnidazole is a promising anti-virulence agent that may be used to control infections caused by .

摘要

是一种引起多种医院感染的机会致病菌。它已对不同抗生素产生了相当大的耐药性,并具备一系列毒力因子。这些毒力因子在一种称为群体感应(QS)的细胞间通讯系统中受到调控。靶向细菌毒力和群体感应是减轻细菌致病性和克服抗菌药物耐药性发展的一种有趣方法。在本研究中,我们旨在评估塞克硝唑对一种临床分离株的抗毒力活性。在体外评估了亚抑菌浓度(亚 MIC)的塞克硝唑对毒力因子、群游运动性、生物膜形成、蛋白酶、溶血素活性和灵菌红素产生的影响。在小鼠体内评估了塞克硝唑对致病性的保护活性。此外,进行了分子对接研究以评估塞克硝唑与SmaR群体感应受体的结合能力。我们的研究结果表明,亚MIC的塞克硝唑在体外显著降低了毒力因子的产生,并减轻了其在小鼠中的致病性。对接研究表明塞克硝唑具有很强的能力竞争性地阻碍自诱导物与SmaR群体感应受体的结合。总之,塞克硝唑是一种有前途的抗毒力药物,可用于控制由引起的感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03fe/8617784/11009a019bec/microorganisms-09-02333-g001.jpg

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