Study on the Inhibitory of Pyruvate-Ferredoxin Oxidoreductase by Luteolin and Its Anti-Clostridium Difficile Effect
10.19378/j.issn.1003-9783.2024.02.010
- VernacularTitle:木犀草素抑制丙酮酸铁氧还蛋白氧化还原酶及其抗艰难梭菌作用研究
- Author:
Lijun XIAO
1
;
Wenjing ZHAO
;
Xiaoyi QI
;
Muhan LYU
;
Sicheng LIANG
Author Information
1. 西南医科大学附属医院消化内科,四川 泸州 646000
- Keywords:
luteolin;
pyruvate-ferredoxin oxidoreductase;
Clostridium difficile;
pyruvate-ferredoxin oxidoreductase(PFOR)
- From:
Traditional Chinese Drug Research & Clinical Pharmacology
2024;35(2):230-236
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effects of pyruvate-ferredoxin oxidoreductase(PFOR)by luteolin and its anti-Clostridium difficile effect.Methods The PFOR encoding sequence of Clostridium difficile was cloned into the expression vector pET-2a and transformed into competent Escherichia coli.The crude enzyme was prepared after induction with IPTG(Isopropyl β-D-Thiogalactoside).The inhibitory rate of the test compounds on PFOR was determined after an 8-hour anaerobic reaction between PFOR and 40 μmol·L-1 of test compounds at 25℃.The minimum inhibitory concentration(MIC)of PFOR inhibitors against C.difficile strains(ATCC BAA 1382 and ATCC BAA 1870)was determined by monitoring the OD600 of the bacterial culture.Molecular docking was performed to investigate the possible interaction mechanisms between PFOR and inhibitors.Results Among the tested compounds,the luteolin showed the strongest inhibitory activity against PFOR,with a single-point inhibition rate of approximately 33%,which is comparable to that observed with the positive inhibitor nitazoxanide(40%).Molecular docking revealed that luteolin could form hydrogen bonds with Asp428,Val431,Gly429,Asp456,Lys458,Lys459,and other residues in the PFOR domain.The MIC of luteolin against C.difficile was approximately 32 μg·mL-1.Conclusion Luteolin exhibits good activity against C.difficile,and PFOR may be a target for its antibacterial action.
