A genome-wide screen reveals the involvement of enterobactin-mediated iron acquisition in Escherichia coli survival during copper stress.
A genome-wide screen reveals the involvement of enterobactin-mediated iron acquisition in Escherichia coli survival during copper stress.
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DOI：
10.1093/mtomcs/mfab052
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发表时间：
2021-09-06
期刊：
影响因子：
--
通讯作者：
Subashchandrabose S
中科院分区：
文献类型：
--
作者：
Casanova-Hampton K;Carey A;Kassam S;Garner A;Donati GL;Thangamani S;Subashchandrabose S
铜（Cu）是一种关键的过渡金属，参与细胞中许多重要的生物过程。铜也被免疫系统利用，以阻碍感染期间病原体的生长。然而，基因组水平上的知识参与适应铜胁迫的机制是有限的。在这里，我们报告的结果，全基因组反向遗传筛选铜反应的表型大肠杆菌。我们的筛选已经确定了新的基因参与适应铜胁迫在E。杆菌我们检测到多个基因参与肠杆菌素的生物合成和摄取，铁载体用于高亲和力TonB依赖性收购铁（Fe），作为关键球员在铜中毒下生存。我们证明了铜的螯合和tonB的遗传互补的铜依赖性杀伤的特异性。值得注意的是，TonB在实验室和尿路致病性大肠杆菌菌株中均参与对Cu的保护。杆菌铜胁迫导致参与铁吸收的基因的表达增加，表明在暴露于过量的铜期间，Fur调节子被去阻遏。微量元素分析表明，铜胁迫期间，铁稳态失调。两者合计，我们的数据支持一个模型，其中缺乏肠杆菌素依赖的铁吸收导致铜毒性加剧，并阐明了细菌细胞中铜和铁的稳态之间的复杂联系。铜胁迫与铁的稳态。杆菌
Copper (Cu) is a key transition metal that is involved in many important biological processes in a cell. Cu is also utilized by the immune system to hamper pathogen growth during infection. However, genome-level knowledge on the mechanisms involved in adaptation to Cu stress is limited. Here, we report the results of a genome-wide reverse genetic screen for Cu-responsive phenotypes in Escherichia coli. Our screen has identified novel genes involved in adaptation to Cu stress in E. coli. We detected multiple genes involved in the biosynthesis and uptake of enterobactin, a siderophore utilized for high-affinity TonB-dependent acquisition of iron (Fe), as critical players in survival under Cu intoxication. We demonstrated the specificity of Cu-dependent killing by chelation of Cu and by genetic complementation of tonB. Notably, TonB is involved in protection from Cu in both laboratory and uropathogenic strains of E. coli. Cu stress leads to increased expression of the genes involved in Fe uptake, indicating that Fur regulon is derepressed during exposure to excess Cu. Trace element analyses revealed that Fe homeostasis is dysregulated during Cu stress. Taken together, our data supports a model in which lack of enterobactin-dependent Fe uptake leads to exacerbation of Cu toxicity, and elucidates the intricate connection between the homeostasis of Cu and Fe in a bacterial cell. Copper Stress and Iron Homeostasis in E. coli.
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DOI：
10.1073/pnas.0607898104
发表时间：
2007-10-16
影响因子：
11.1
作者：
Lane, M. Chelsea;Alteri, Christopher J.;Mobley, Harry L. T.
通讯作者：
Mobley, Harry L. T.
影响因子：
14.8
作者：
Chaturvedi, Kaveri S.;Hung, Chia S.;Crowley, Jan R.;Stapleton, Ann E.;Henderson, Jeffrey P.
通讯作者：
Henderson, Jeffrey P.
影响因子：
10.5
作者：
Guo MS;Updegrove TB;Gogol EB;Shabalina SA;Gross CA;Storz G
通讯作者：
Storz G
影响因子：
3.1
作者：
Hyre, Amanda N.;Kavanagh, Kylie;Subashchandrabose, Sargurunathan
通讯作者：
Subashchandrabose, Sargurunathan
影响因子：
4.8
作者：
Fontenot, Chelsey R.;Tasnim, Homyra;Ding, Huangen
通讯作者：
Ding, Huangen