Metabolic Reprogramming of Vibrio cholerae Impaired in Respiratory NADH Oxidation Is Accompanied by Increased Copper Sensitivity
Metabolic Reprogramming of Vibrio cholerae Impaired in Respiratory NADH Oxidation Is Accompanied by Increased Copper Sensitivity
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霍乱弧菌的代谢重编程因呼吸 NADH 氧化受损而伴有铜敏感性增加
DOI：
10.1128/jb.00761-17
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发表时间：
2018
影响因子：
3.2
通讯作者：
Steuber J
中科院分区：
文献类型：
--
作者：
Toulouse C;Metesch K;Pfannstiel J;Steuber J
霍乱弧菌的产电、钠离子转运的NADH：Q氧化还原酶(NQR)在病原菌中很常见，也是抗生素的潜在靶点。NQR将NADH的氧化与钠动力(SMF)的形成耦合起来，从而驱动重要的过程，如鞭毛旋转、底物摄取和能量耗散的阳离子-质子对流。我们对霍乱弧菌O395N1及其缺失NQR的变异体进行了定量蛋白质组分析，以葡萄糖为碳源的微量培养基作对照。我们发现84个蛋白质(≥-2的调节因子)发生了丰度的变化。NQR的缺失导致三羧酸(TCA)循环氧化支链中酶的丰度降低，毒力因子ACFC和TCPA的丰度增加。最令人意想不到的是，铜抗性蛋白CopA、CopG和CueR在缺失菌株中降低。结果，突变株与参考菌株相比，对铜的抗性降低，这在使用葡萄糖或混合氨基酸作为碳源的生长研究中得到了证实。我们认为，观察到的qr缺失菌株的适应代表了一种协调反应，这种反应抵消了跨膜电压的下降，后者在不同的栖息地挑战霍乱弧菌。重要的是，中枢代谢对细菌毒力的重要性已经引起了人们对研究宿主中不存在的分解代谢酶的兴趣，例如NQR，作为抗生素的假定靶标。缺乏NQR的霍乱弧菌是一个评估特定NQR抑制剂对病原体表型影响的模型。我们的比较蛋白质组学研究为评估针对NQR的化合物在其抑菌或杀菌作用方面的成功机会提供了一个框架。
The electrogenic, sodium ion-translocating NADH:quinone oxidoreductase (NQR) from Vibrio cholerae is frequent in pathogenic bacteria and a potential target for antibiotics. NQR couples the oxidation of NADH to the formation of a sodium motive force (SMF) and therefore drives important processes, such as flagellar rotation, substrate uptake, and energy-dissipating cation-proton antiport. We performed a quantitative proteome analysis of V. cholerae O395N1 compared to its variant lacking the NQR using minimal medium with glucose as the carbon source. We found 84 proteins (regulation factor of ≥2) to be changed in abundance. The loss of NQR resulted in a decrease in the abundance of enzymes of the oxidative branch of the tricarboxylic acid (TCA) cycle and an increase in abundance of virulence factors AcfC and TcpA. Most unexpected, the copper resistance proteins CopA, CopG, and CueR were decreased in thenqrdeletion strain. As a consequence, the mutant exhibited diminished resistance to copper compared to the reference strain, as confirmed in growth studies using either glucose or mixed amino acids as carbon sources. We propose that the observed adaptations of thenqrdeletion strain represent a coordinated response which counteracts a drop in transmembrane voltage that challenges V. cholerae in its different habitats.IMPORTANCEThe importance of the central metabolism for bacterial virulence has raised interest in studying catabolic enzymes not present in the host, such as NQR, as putative targets for antibiotics. Vibrio cholerae lacking the NQR, which is studied here, is a model to estimate the impact of specific NQR inhibitors on the phenotype of a pathogen. Our comparative proteomic study provides a framework to evaluate the chances of success of compounds directed against NQR with respect to their bacteriostatic or bactericidal action.
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DOI：
10.1007/s004380050718
发表时间：
1998
期刊：
Molecular and General Genetics MGG
影响因子：
--
作者：
A. Mademidis;W. Köster
通讯作者：
W. Köster
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影响因子：
3.2
作者：
V. Muras;Paul Dogaru;Yusuke Minato;C. Häse;J. Steuber
通讯作者：
J. Steuber
Na( )-转位 NADH:醌氧化还原酶在霍乱弧菌电压产生和 Na( ) 挤出中的作用
DOI：
10.1016/j.bbabio.2015.12.010
发表时间：
2016
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Vorburger;Nedielkov;Brosig;Schunke;Steffen;Möller;Steuber
通讯作者：
Steuber
影响因子：
3.2
作者：
Halang, Petra;Toulouse, Charlotte;Steuber, Julia
通讯作者：
Steuber, Julia
影响因子：
3.9
作者：
L. Wu;M. Mandrand-Berthelot
通讯作者：
L. Wu;M. Mandrand-Berthelot