Synergism of paclitaxel and colistin against Escherichia coli and the synergistic mechanism
10.16303/j.cnki.1005-4545.2025.03.24
- VernacularTitle:紫杉醇与黏菌素联用对大肠杆菌的协同作用及增效机制
- Author:
Xueqin HU
1
;
Changjian FAN
1
;
Qibiao HE
1
;
Peiyi LIU
1
;
Dandan HE
1
;
Hua WU
1
;
Xiaoyuan MA
1
;
Gongzheng HU
1
;
Yajun ZHAI
1
Author Information
1. 河南农业大学动物医学院,河南郑州 450046
- Publication Type:Journal Article
- Keywords:
paclitaxel;
colistin;
drug combination;
E.coli;
synergistic effect
- From:
Chinese Journal of Veterinary Science
2025;45(3):580-586
- CountryChina
- Language:Chinese
-
Abstract:
To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.
