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Metabonomics reveals an alleviation of fitness cost in resistant E. coli competing against susceptible E. coli at sub-MIC doxycycline

文献类型： 外文期刊

作者： Wen, Xin 1 ; Cao, Junchao 1 ; Mi, Jiandui 1 ; Huang, Jielan 1 ; Liang, Jiadi 1 ; Wang, Yan 1 ; Ma, Baohua 7 ; Zou, Yongde 7 ;

作者机构： 1.South China Agr Univ, Coll Anim Sci, Guangdong Lab Lingnan Modern Agr, Guangzhou 510642, Peoples R China

2.South China Agr Univ, Natl Engn Res Ctr Breeding Swine Ind, Guangzhou 510642, Peoples R China

3.Minist Agr, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Guangzhou 510642, Guangdong, Peoples R China

4.Minist Agr, Key Lab Chicken Genet Breeding & Reprod, Guangzhou 510642, Guangdong, Peoples R China

5.South China Agr Univ, Minist Agr, Key Lab Trop Agr Environm, Guangzhou 510642, Peoples R China

6.Guangdong Engn Technol Res Ctr Harmless Treatment, Yunfu 527400, Xinxing, Peoples R China

7.Foshan Customs Comprehens Technol Ctr, Foshan 528200, Peoples R China

8.Univ Putra Malaysia, Inst Trop Agr, Lab Anim Prod, Serdang 43400, Malaysia

关键词： Resistant bacteria; Susceptible bacteria; Fitness cost; Metabolic mechanism; Sub-MIC

期刊名称：JOURNAL OF HAZARDOUS MATERIALS （ 影响因子：10.588； 五年影响因子：10.129 ）

ISSN： 0304-3894

年卷期： 2021 年 405 卷

页码：

收录情况： SCI

摘要： High concentrations of antibiotics may induce bacterial resistance mutations and further lead to fitness costs by reducing growth of resistant bacteria. However, antibiotic concentrations faced by bacteria are usually low in common environments, which leads to questions about how resistant bacteria with fitness costs regulate metabolism to coexist or compete with susceptible bacteria during sublethal challenge. Our study revealed that a low proportion (< 15%) of resistant bacteria coexisted with susceptible bacteria due to the fitness cost without doxycycline. However, the cost for the resistant strain decreased at a doxycycline concentration of 1 mg/L and even disappeared when the doxycycline concentration was 2 mg/L. Metabonomics analysis revealed that bypass carbon metabolism and biosynthesis of secondary metabolites were the primary metabolic pathways enriching various upregulated metabolites in resistant bacteria without doxycycline. Moreover, the alleviation of fitness cost for resistant bacteria competed with susceptible bacteria at 1 mg/L doxycycline was correlated with the downregulation of the biomarkers pyruvate and pilocarpine. Our study offered new insight into the metabolic mechanisms by which the fitness cost of resistant mutants was reduced at doxycycline concentrations as low as 1 mg/L and identified various potential metabolites to limit the spread of antimicrobial resistance in the environment.

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