Transient Glycolytic Complexation of Arsenate Enhances Resistance in the Enteropathogen Vibrio cholerae.
Transient Glycolytic Complexation of Arsenate Enhances Resistance in the Enteropathogen Vibrio cholerae.
复制标题
作者：
有毒砷酸盐（AsV）在环境中的普遍存在，提高了所有生物体的抵抗机制。一般来说，细菌解毒的AsV依赖于它的还原亚砷酸盐（AsIII）的ArsC，其次是出口的AsIII的ArsB。然而，致病物种如何抵抗这种类金属仍然是未知的。在这里，我们发现，霍乱弧菌，霍乱弧菌的病原体，胜过其他肠道病原体时，生长在毫摩尔浓度的AsV。为了做到这一点，霍乱弧菌使用AsV诱导的vc 1068 -1071操纵子（因砷酸弧菌抗性而更名为var）代替ArsCB，该操纵子编码砷酸盐阻遏物ArsR、替代甘油醛-3-磷酸脱氢酶、推定的磷酸酶和AsV转运蛋白ArsJ。除Var外，霍乱弧菌还诱导氧化应激相关系统，以对抗细胞内AsV引起的活性氧（ROS）产生。var突变体的表征表明，这些蛋白质的功能彼此独立，并在防止有害影响的细胞膜电位和生长来自积累AsV中发挥关键作用。从机理上讲，我们证明了霍乱弧菌与糖酵解中间体3-磷酸甘油酸盐复合成1-砷基-3-磷酸甘油酸盐（1As 3 PG）。我们进一步表明，1As 3 PG不被运输到细胞外，相反，它随后被解离，使自由AsV通过ArsJ挤出。总的来说，我们建议形成1As 3 PG作为一个短暂的代谢储存的AsV，以遏制有害的影响，免费的AsV。这项研究推进了我们对细菌中AsV耐药性的理解，并强调了新的脆弱点，这可能是抗菌干预的一个有吸引力的目标。
The ubiquitous presence of toxic arsenate (AsV) in the environment has raised mechanisms of resistance in all living organisms. Generally, bacterial detoxification of AsV relies on its reduction to arsenite (AsIII) by ArsC, followed by the export of AsIII by ArsB. However, how pathogenic species resist this metalloid remains largely unknown. Here, we found that Vibrio cholerae, the etiologic agent of the diarrheal disease cholera, outcompetes other enteropathogens when grown on millimolar concentrations of AsV. To do so, V. cholerae uses, instead of ArsCB, the AsV-inducible vc1068-1071 operon (renamed var for vibrio arsenate resistance), which encodes the arsenate repressor ArsR, an alternative glyceraldehyde-3-phosphate dehydrogenase, a putative phosphatase, and the AsV transporter ArsJ. In addition to Var, V. cholerae induces oxidative stress-related systems to counter reactive oxygen species (ROS) production caused by intracellular AsV. Characterization of the var mutants suggested that these proteins function independently from one another and play critical roles in preventing deleterious effects on the cell membrane potential and growth derived from the accumulation AsV. Mechanistically, we demonstrate that V. cholerae complexes AsV with the glycolytic intermediate 3-phosphoglycerate into 1-arseno-3-phosphoglycerate (1As3PG). We further show that 1As3PG is not transported outside the cell; instead, it is subsequently dissociated to enable extrusion of free AsV through ArsJ. Collectively, we propose the formation of 1As3PG as a transient metabolic storage of AsV to curb the noxious effect of free AsV. This study advances our understanding of AsV resistance in bacteria and underscores new points of vulnerability that might be an attractive target for antimicrobial interventions.
登录
查看更多内容
DOI：
10.3390/molecules20058742
发表时间：
2015-05-14
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Aoyama K;Nakaki T
通讯作者：
Nakaki T
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1073/pnas.0803281105
发表时间：
2008-06-24
影响因子：
11.1
作者：
Cameron, D. Ewen;Urbach, Jonathan M.;Mekalanos, John J.
通讯作者：
Mekalanos, John J.
影响因子：
3.6
作者：
Chen J;Yoshinaga M;Garbinski LD;Rosen BP
通讯作者：
Rosen BP
影响因子：
3.1
作者：
DONNENBERG, MS;KAPER, JB
通讯作者：
KAPER, JB