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氟噻嗪酮抑制参与尿路感染发生的尿路致病性大肠杆菌的毒力因子。

Fluorothiazinon inhibits the virulence factors of uropathogenic Escherichia coli involved in the development of urinary tract infection.

作者信息

Koroleva E A, Soloveva A V, Morgunova E Y, Kapotina L N, Luyksaar S I, Luyksaar S V, Bondareva N E, Nelubina S A, Lubenec N L, Zigangirova N A, Gintsburg A L

机构信息

National Research Center of Epidemiology and Microbiology n. a. N.F. Gamaleya, Russian Ministry of Health, Moscow, 123098, Russia.

I.M. Sechenov First Moscow State Medical University, Moscow, 119992, Russia.

出版信息

J Antibiot (Tokyo). 2023 May;76(5):279-290. doi: 10.1038/s41429-023-00602-5. Epub 2023 Mar 15.

Abstract

Uropathogenic Escherichia coli (UPEC) is the most common pathogenic bacterium associated with urinary tract infection. Due to the development of antibiotic resistance and MDR, UPEC infection has become a serious problem in the last decade. In order to combat resistance, it is necessary to develop innovative antimicrobial agents that act by different mechanisms than conventional antibiotics. Among the new therapeutic strategies, suppression of pathogen virulence has become a promising alternative, since it fundamentally reduces selective pressure and the development of resistance. In our study, we showed that the compound Fluorothiazinon suppressed UPEC's ability to form biofilms and to move using the flagellum, as well as to penetrate into cells. Prophylactic use with subsequent treatment of FT in rodent models led to an improvement in survival and significantly reduced the bacterial load in the organs of the urinary system, thereby inhibiting the development of ascending infection and preventing the development of pathological changes in prostate tissues. These results suggest that FT affects several UPEC virulence factors at once and if similar results can be found in clinical trials it can potentially be used as a new drug against UPEC.

摘要

尿路致病性大肠杆菌(UPEC)是与尿路感染相关的最常见病原菌。由于抗生素耐药性和多重耐药性的发展,UPEC感染在过去十年中已成为一个严重问题。为了对抗耐药性,有必要开发通过与传统抗生素不同机制起作用的创新抗菌剂。在新的治疗策略中,抑制病原体毒力已成为一种有前景的替代方法,因为它从根本上降低了选择性压力和耐药性的发展。在我们的研究中,我们表明化合物氟噻嗪酮抑制了UPEC形成生物膜、利用鞭毛移动以及侵入细胞的能力。在啮齿动物模型中预防性使用氟噻嗪酮并随后进行治疗可提高生存率,并显著降低泌尿系统器官中的细菌载量,从而抑制上行感染的发展并预防前列腺组织中病理变化的发生。这些结果表明氟噻嗪酮同时影响多种UPEC毒力因子,如果在临床试验中能发现类似结果,它有可能用作抗UPEC的新药。

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