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Research Note: Synergistic effect of isopropoxy benzene guanidine and colistin against mcr-1-positive Escherichia coli in vitro and in duck intestine infection models

文献类型： 外文期刊

作者： Li, Yafei 3 ; Niu, Huijun 1 ; Huang, Lang 1 ; Zhang, Lingxuan 1 ; Mao, Lingxiang 1 ; Wan, Peng 1 ; Ma, Zhenbao 1 ; Peng, Xianfeng 2 ; Wan, Kai 3 ; Zeng, Zhenling 1 ;

作者机构： 1.Guangdong Acad Agr Sci, Inst Qual Stand & Monitoring Technol Agroprod, Guangzhou 510640, Peoples R China

2.South China Agr Univ, Coll Vet Med, Guangdong Prov Key Lab Vet Pharmaceut Dev & Safety, Guangzhou 510642, Peoples R China

3.Guangzhou Insighter Biotechnol Co Ltd, Guangzhou 510663, Peoples R China

4.Guangdong Prov Key Lab Qual & Safety Risk Assessme, Guangzhou 510640, Peoples R China

关键词： isopropoxy benzene guanidine; colistin; mcr-1; duck; resistance

期刊名称：POULTRY SCIENCE （ 影响因子：3.8； 五年影响因子：4.1 ）

ISSN： 0032-5791

年卷期： 2024 年 103 卷 9 期

页码：

收录情况： SCI

摘要： Colistin (CST) is considered as "agent of last resort" against gram-negative bacteria as feed additive. Its clinical effectiveness has reduced since the emergence of mcr-1 gene in ducks. Isopropoxy benzene guanidine (IBG), a new guanidine derivative, showed positive effects on improving animal weights and alleviating intestinal pathogens, therefore, the objective of this study was to evaluate the effect of this compound supplement with CST in ducks and explore the possibilities in feed additive. A total of fifteen duck-origin Escherichia coli carrying the mcr-1 gene were included in this study. A checkerboard microdilution assay was used to evaluate the in vitro antibacterial activity of IBG combined with CST against mcr-1-positive E. coli. . A 3-by-2 time-kill array of IBG (16, 32, and 64 mg/mL) and CST (1/2 MIC and 1/4 MIC) over 24 hours was utilized to characterize the activity of the agents alone and in combination against E. coli strain 1 in vitro. . The intestinal colonization model was used to evaluate the in vivo effect of IBG combined with CST. These results indicated that the combination of IBG plus CST showed a synergistic effect against all clinical isolates (FICI < 0.5). The bacterial burden was reduced by more than 2 log10 CFU/mL when E. coli strain 1 was tested with 1/2 MIC CST plus 64 mg/mL IBG for 24 h. Further experiments in vivo demonstrated that the CST combined with IBG was able to increase duck weights, reduced intestinal pathogenic E. coli and showed a synergistic antibacterial effect. Combination of CST (4 mg/kg b.w.) plus IBG (32 or 64 mg/kg b.w.) achieved 1.84 to 3.29 log10 CFU/g killing after 7 d of therapy, which was significantly different from that in the challenge control group (p<0.05). In summary, our study demonstrated the potential use of IBG as feed additive for veterinary purposes in ducks and provided new insights into overcoming resistance in the future.

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