Quercitrin Is a Novel Inhibitor of Salmonella enterica Serovar Typhimurium Type III Secretion System
文献类型: 外文期刊
作者: Li, Qingjie 1 ; Wang, Lianping 2 ; Xu, Jingwen 3 ; Liu, Shuang 4 ; Song, Zeyu 3 ; Chen, Tingting 3 ; Deng, Xuming 3 ; Wang, Jianfeng 3 ; Lv, Qianghua 3 ;
作者机构: 1.Changchun Univ Chinses Med, Affiliated Hosp, Res Ctr Tradit Chinese Med, Changchun 130021, Peoples R China
2.Jilin Agr Sci & Technol Univ, Sch Tradit Chinese Med, Changchun 132101, Peoples R China
3.Jilin Univ, Coll Vet Med, State Key Lab Diag & Treatment Severe Zoonot Infec, Key Lab Zoonosis Res,Minist Educ,Inst Zoonosis, Changchun 130062, Peoples R China
4.Jilin Jinziyuan Biotech Inc, Shuangliao 136400, Peoples R China
5.Shandong Acad Agr Sci, Inst Anim Sci & Vet Med, Jinan 250100, Peoples R China
关键词: Salmonella enterica serovar Typhimurium; type III secretion system; T3SS inhibitor; anti-virulence; quercitrin
期刊名称:MOLECULES ( 影响因子:4.6; 五年影响因子:4.9 )
ISSN:
年卷期: 2023 年 28 卷 14 期
页码:
收录情况: SCI
摘要: The purpose was to screen type III secretory system (T3SS) inhibitors of Salmonella enterica serovar Typhimurium (S. Typhimurium) from natural compounds. The pharmacological activities and action mechanisms of candidate compounds in vivo and in vitro were systematically studied and analyzed. Using a SipA-& beta;-lactamase fusion reporting system, we found that quercitrin significantly blocked the translocation of SipA into eukaryotic host cells without affecting the growth of bacteria. Adhesion and invasion assay showed that quercitrin inhibited S. Typhimurium invasion into host cells and reduced S. Typhimurium mediated host cell damage. & beta;-galactosidase activity detection and Western blot analysis showed that quercitrin significantly inhibited the expression of SPI-1 genes (hilA and sopA) and effectors (SipA and SipC). The results of animal experiments showed that quercitrin significantly reduced colony colonization and alleviated the cecum pathological injury of the infected mice. Small molecule inhibitor quercitrin directly inhibited the function of T3SS and provided a potential antibiotic alternative against S. Typhimurium infection. Importance: T3SS plays a crucial role in the bacterial invasion and pathogenesis of S. Typhimurium. Compared with conventional antibiotics, small molecules could inhibit the virulence factors represented by S. Typhimurium T3SS. They have less pressure on bacterial vitality and a lower probability of producing drug resistance. Our results provide strong evidence for the development of novel inhibitors against S. Typhimurium infection.
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