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哈尔明,沙门氏菌血清型 Typhimurium III 型分泌系统的抑制剂。

Harmine, an inhibitor of the type III secretion system of serovar Typhimurium.

机构信息

Laboratory for Zoonotic Diseases, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

Department of Respiratory Medicine, Center for Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Zoonotic Diseases, The First Hospital of Jilin University, Changchun, China.

出版信息

Front Cell Infect Microbiol. 2022 Sep 13;12:967149. doi: 10.3389/fcimb.2022.967149. eCollection 2022.

Abstract

New therapeutic strategies for clinical serovar Typhimurium ( Typhimurium) infection are urgently needed due to the generation of antibiotic-resistant bacteria. Inhibition of bacterial virulence has been increasingly regarded as a potential and innovative strategy for the development of anti-infection drugs. pathogenicity island (SPI)-encoded type III secretion system (T3SS) represents a key virulence factor in Typhimurium, and active invasion and replication in host cells is facilitated by the secretion of T3SS effector proteins. In this study, we found that harmine could inhibit T3SS secretion; thus, its potential anti-. Typhimurium infection activity was elucidated. Harmine inhibits the secretion and expression of T3SS effector proteins and consequently attenuates the Typhimurium invasion function of HeLa cells. This inhibition may be implemented by reducing the transcription of pathogenesis-related SPI-1 transcriptional activator genes , , and . Harmine improves the survival rate and bacterial loads of mice infected with . Typhimurium. In summary, harmine, an effective T3SS inhibitor, could be a leading compound for the development of treatments for infection.

摘要

由于抗生素耐药菌的产生,迫切需要针对临床鼠伤寒沙门氏菌(鼠伤寒沙门氏菌)感染的新治疗策略。抑制细菌毒力已越来越被视为开发抗感染药物的一种潜在和创新策略。毒力岛(SPI)编码的 III 型分泌系统(T3SS)是鼠伤寒沙门氏菌的一个关键毒力因子,通过 T3SS 效应蛋白的分泌促进了在宿主细胞中的主动侵袭和复制。在这项研究中,我们发现猪毛菜碱可抑制 T3SS 分泌;因此,阐明了其潜在的抗鼠伤寒沙门氏菌感染活性。猪毛菜碱抑制 T3SS 效应蛋白的分泌和表达,从而减弱了鼠伤寒沙门氏菌对 HeLa 细胞的侵袭功能。这种抑制作用可能是通过减少与发病机制相关的 SPI-1 转录激活基因的转录来实现的。猪毛菜碱提高了感染鼠伤寒沙门氏菌的小鼠的存活率和细菌负荷。总之,作为一种有效的 T3SS 抑制剂,猪毛菜碱可能成为开发治疗鼠伤寒沙门氏菌感染的先导化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7943/9513467/cc910c6c7ffb/fcimb-12-967149-g001.jpg

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