Role and mechanism of the outer membrane porin LamB in T-2 mycotoxin-mediated extensive drug resistance in Escherichia coli

文献类型： 外文期刊

第一作者： Deng, Fengru

作者： Deng, Fengru;Zhao, Li;Wei, Ping;Mai, Enhua;Chen, Meichan;Yang, Huixin;Mu, Peiqiang;Wu, Jun;Wen, Jikai;Deng, Yiqun;Deng, Yiqun

作者机构：

关键词： T-2 mycotoxin; Extensively drug-resistant (XDR) E. coli; Specific porin LamB; Membrane permeability; Last-resort antibiotics

期刊名称：JOURNAL OF HAZARDOUS MATERIALS （ 影响因子：11.3； 五年影响因子：12.4 ）

ISSN： 0304-3894

年卷期： 2024 年 480 卷

页码：

收录情况： SCI

摘要： The influence of mycotoxins in ecological niches shared with antibiotic-resistant bacteria (ARB) remains underexplored. This study examined the impact of T-2 mycotoxin on the evolution of antibiotic resistance in Escherichia coli, highlighting the role of specific porins. Our findings revealed that exposure to 10 ng/mL of T-2 toxin induced multi-drug resistant (MDR) phenotypes in three E. coli. At 10(-5) ng/mL, T-2 toxin caused E. coli ATCC 25922 to develop stable resistance to 13 critical antibiotics, with minimum inhibitory concentrations (MICs) increasing 16- to several thousand-fold. This resistance was linked to the downregulation of the mal gene cluster. Notably, T-2 toxin reduced membrane permeability by downregulating lamB, facilitating its own entry and reducing the intracellular accumulation of both the toxin and antibiotics, thereby enhancing resistance development. LamB mediated the XDR phenotypes in E. coli, particularly by blocking last-resort antibiotics such as cephalosporins, carbapenems, tigecycline, and colistin, complicating treatment strategies. LamB demonstrated high binding affinities for T-2 toxin and various antibiotics, with specific binding sites identified for meropenem (Arg134), imipenem (Ser148, Arg170, Lys129), ceftazidime (Phe106, Lys129), and cefepime (Tyr66, Gln267, Lys269), exhibiting binding energies of -2.93, -2.58, -2.53, and -4.3, respectively. These findings suggest that even low levels of T-2 mycotoxin pose a substantial public health risk. They underscore the urgent need to address these contaminants and open new avenues for antibiotic resistance research.

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