A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress.
A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress.
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DOI：
10.1111/mmi.12597
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发表时间：
2014-05
影响因子：
3.6
通讯作者：
Law CJ
中科院分区：
文献类型：
--
作者：
Paul S;Alegre KO;Holdsworth SR;Rice M;Brown JA;McVeigh P;Kelly SM;Law CJ
人体肠道对高浓度胆汁盐的抵抗力对于大肠杆菌等肠道细菌的生存至关重要。尽管三方 AcrAB-TolC 外排系统在这种阻力中发挥着重要作用，但据称其他外排泵也必须参与其中。我们提供了在两个不同 pH 值（7.2 和 6.0）下进行的一系列综合实验的证据，这些实验反映了大肠杆菌的 pH 条件。大肠杆菌可能在人类肠道中遇到 MdtM（主要促进子超家族的单组分多药耐药转运蛋白），在大肠杆菌中发挥胆汁盐耐药性的作用。大肠杆菌通过催化胆汁盐从细胞质中二次主动转运。此外，对用编码 MdtM 的多拷贝质粒转化的染色体 ΔacrB 突变体进行的测定表明，单组分 MdtM 转运蛋白和三方 AcrAB-TolC 系统之间存在功能协同作用，从而对耐药性产生倍增效应。对纯化的 MdtM 进行的底物结合实验表明，转运蛋白以微摩尔亲和力与胆酸盐和脱氧胆酸盐结合，对倒转囊泡进行的转运测定证实了 MdtM 催化产电胆汁盐/H+反向转运的能力。
Resistance to high concentrations of bile salts in the human intestinal tract is vital for the survival of enteric bacteria such as E scherichia coli. Although the tripartite AcrAB–TolC efflux system plays a significant role in this resistance, it is purported that other efflux pumps must also be involved. We provide evidence from a comprehensive suite of experiments performed at two different pH values (7.2 and 6.0) that reflect pH conditions that E . coli may encounter in human gut that MdtM, a single-component multidrug resistance transporter of the major facilitator superfamily, functions in bile salt resistance in E . coli by catalysing secondary active transport of bile salts out of the cell cytoplasm. Furthermore, assays performed on a chromosomal ΔacrB mutant transformed with multicopy plasmid encoding MdtM suggested a functional synergism between the single-component MdtM transporter and the tripartite AcrAB–TolC system that results in a multiplicative effect on resistance. Substrate binding experiments performed on purified MdtM demonstrated that the transporter binds to cholate and deoxycholate with micromolar affinity, and transport assays performed on inverted vesicles confirmed the capacity of MdtM to catalyse electrogenic bile salt/H+ antiport.
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影响因子：
3.9
作者：
Holdsworth, Scarlett R.;Law, Christopher J.
通讯作者：
Law, Christopher J.
影响因子：
3.1
作者：
MCDOUGALL, CJ;WONG, R;DECOSSE, JJ
通讯作者：
DECOSSE, JJ
影响因子：
4
作者：
Bron, PA;Molenaar, D;Kleerebezem, M
通讯作者：
Kleerebezem, M
影响因子：
3.2
作者：
Edgar, R;Bibi, E
通讯作者：
Bibi, E
影响因子：
3.7
作者：
Kalantzi, L;Goumas, K;Reppas, C
通讯作者：
Reppas, C