The cytochrome P4501A1(CYP1A1)inhibitor bergamottin enhances host tolerance to multidrug-resistant Vibrio vulnificus infection  

作　　者：Ruo-Bai Qiao Wei-Hong Dai Wei Li Xue Yang Dong-Mei He Rui Gao Yin-Qin Cui Ri-Xing Wang Xiao-Yuan Ma Fang-Jie Wang Hua-Ping Liang 

机构地区：[1]The College of Emergency and Trauma,Hainan Medical University,Haikou,571199,China [2]The First Research Department,State Key Laboratory of Trauma and Chemical Poisoning,Army Medical Center(Daping Hospital),Army Medical University,Chongqing,400042,China [3]Emergency Department,The Second Affiliated Hospital,Hainan Medical University,Haikou,570311,China

出　　处：《Chinese Journal of Traumatology》2024年第5期295-304,共10页中华创伤杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(grant number:82104247);Chongqing Talent Innovation Leading Plan(grant number:cstc2021ycjhbgzxm0340);Chongqing Doctor Express Project(grant number:CSTB2022BSXM-JCX0024);Hainan Clinical Medical Research Center Project(grant number:LCYX202205);Hainan Province Health Industry Research Project(grant number:22A200082).

摘　　要：Purpose:Vibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body''s infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistantV. Vulnificus and the protection of their vital organs.Methods:An increasing concentration gradient method was used to induce multidrug-resistantV. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistantV. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues a

关 键 词：Multidrug-resistant Vibrio vulnificus Bergamottin CYP1A1 inhibitors Infection tolerance 

分 类 号：R515[医药卫生—内科学]