Research on the Synergistic Enhancement of the In Vitro Bactericidal Effect of Tigecycline-resistant CRKP by Traditional Chinese Medicine Radix Sophorae Flavescentis and Its Mechanism
10.3969/j.issn.1671-7414.2025.06.032
- VernacularTitle:中药苦参协同增强对替加环素耐药CRKP的体外抑菌作用及机制研究
- Author:
Huanyu ZHOU
1
;
Huiyan WU
1
;
Yilin GUAN
1
Author Information
1. 广州医科大学附属第五医院,广州 510700;广州医科大学金域检验学院,广州 510180
- Publication Type:Journal Article
- Keywords:
Radix Sophorae Flavescentis;
tegacycline;
carbapenem-resistant Klebsiella pneumoniae;
AcrAB-TolC e?ux pump
- From:
Journal of Modern Laboratory Medicine
2025;40(6):176-180
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the in vitro antibacterial effect of Radix Sophorae Flavescentis on tigecycline-resistant carbapenem-resistant Klebsiella pneumonia(CRKP)and elucidate how Radix Sophorae Flavescentis restores the sensitivity of CRKP to tigecycline through the efflux pump pathway.Methods The CRKP standard strain BAA1705 was induced to be tigecycline-resistant using the microdilution broth method,and the expression of efflux pumps was verified by efflux pump inhibitors.The fractional inhibitory concentration index(FIC)was calculated using the microdilution checkerboard method to determine the minimum inhibitory concertration(MIC)of the two drugs in combination.Fluorescent real-time quantitative PCR(qRT-PCR)was used to analyze the expression of the AcrB gene before and after Radix Sophorae Flavescentis treatment,and the e?ux pump activity was validated by the Rhodamine 6G e?ux assay.Results The e?ux pump inhibition experiment on the artificially induced T-BAA1705 strain showed overexpression of e?ux pumps.The combined antibacterial test results indicated synergy between Radix Sophorae Flavescentis and tigecycline(FIC=0.375 2).The qRT-PCR results showed that the AcrB levels in the Radix Sophorae Flavescentis monotherapy group were lower than in the untreated group(0.018±0.002 vs 0.040±0.001),and the AcrB levels(0.009±0.001),RamA levels(0.184±0.003)and MarA(0.013±0.001)levels in the combination therapy group were all lower than in the untreated group(0.040±0.001,0.387±0.016,0.125±0.007),while the AcrR level was higher than in the untreated group(0.388±0.001 vs 0.288±0.001),and the differences were statistical significance(t=12.28～47.12,all P<0.05);the e?ux pump activity in the Radix Sophorae Flavescentis monotherapy group and the combination therapy group was lower than in the untreated T-BAA1705(60.667±0.448,60.267±0.376,65.133±0.296),and the differences were statistical significance(t=8.31,10.17,all P<0.05).Conclusion Radix Sophorae Flavescentis can restore the sensitivity of tigecycline-resistant CRKP to tigecycline and effectively inhibit bacterial growth when used in combination with tigecycline.The mechanism may involve Radix Sophorae Flavescentis inhibiting the expression of the AcrAB-TolC e?ux pump.
