Staphylococcus aureus lacking a functional MntABC manganese import system has increased resistance to copper.
Staphylococcus aureus lacking a functional MntABC manganese import system has increased resistance to copper.
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DOI：
10.1111/mmi.14623
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发表时间：
2021-04
影响因子：
3.6
通讯作者：
Boyd JM
中科院分区：
文献类型：
--
作者：
Al-Tameemi H;Beavers WN;Norambuena J;Skaar EP;Boyd JM
S.金黄色葡萄球菌USA300分离株利用copBL和copAZ基因产物来防止Cu中毒。我们创建并检查了Δ copAZ Δ copBL突变株（cop-）。cop-1菌株对铜敏感，具有细胞内铜积累的特性.我们在cop背景中筛选转座子（Tn）突变体文库，并分离在mntABC操纵子中具有Tn插入的菌株，其允许在Cu存在下生长。这些突变发生在mntA中，并且是隐性的。在所使用的生长条件下，MntABC在锰（Mn）输入中起作用。当与Cu一起培养时，含有mntA：：Tn的菌株比亲本菌株积累更少的Cu。Mn（II）补充改善了当COP-与Cu一起培养时的生长，并且这种表型依赖于MntR的存在，MntR是mntABC转录的阻遏物。Δ mntR菌株在Cu存在下具有增加的Cu负荷和降低的生长，这通过引入mntA：：Tn而消除。mntABC的过度表达增加了细胞的铜负荷和对铜的敏感性。mntA：：Tn突变的存在保护铁硫（FeS）酶不被Cu灭活。所呈现的数据与其中缺陷MntABC导致细胞Cu积累减少和保护FeS酶免受Cu中毒的模型一致。为了对抗抗生素耐药性，我们需要开发新的预防和治疗方法。铜（Cu）已显示出作为抗菌化合物的前景;然而，关于Cu如何进入细胞，杀死微生物以及微生物如何防止Cu中毒的问题仍然存在。在这里，我们目前的数据表明，功能障碍MntABC锰转运蛋白的结果在细胞铜积累减少。我们还表明，细胞溶质铜积累抑制S。金黄色葡萄球菌FeS酶。
S. aureus USA300 isolates utilize the copBL and copAZ gene products to prevent Cu intoxication. We created and examined a ΔcopAZ ΔcopBL mutant strain (cop-). The cop- strain was sensitive to Cu and accumulated intracellular Cu. We screened a transposon (Tn) mutant library in the cop- background and isolated strains with Tn insertions in the mntABC operon that permitted growth in the presence of Cu. The mutations were in mntA and they were recessive. Under the growth conditions utilized, MntABC functioned in manganese (Mn) import. When cultured with Cu, strains containing a mntA::Tn accumulated less Cu than the parent strain. Mn(II) supplementation improved growth when cop- was cultured with Cu and this phenotype was dependent upon the presence of MntR, which is a repressor of mntABC transcription. A ΔmntR strain had an increased Cu load and decreased growth in the presence of Cu, which was abrogated by introduction of mntA::Tn. Over-expression of mntABC increased cellular Cu load and sensitivity to Cu. The presence of a mntA::Tn mutation protected iron-sulfur (FeS) enzymes from inactivation by Cu. The data presented are consistent with a model wherein defective MntABC results in decreased cellular Cu accumulation and protection to FeS enzymes from Cu poisoning. To combat antibiotic resistance, we need to develop new prevention and therapeutic approaches. Copper (Cu) has shown promise as an antimicrobial compound; however, questions remain about how Cu enters cells, kills microorganisms, and how microorganisms prevent intoxication by Cu. Here we present data showing that a dysfunctional MntABC Mn transporter results in decreased cellular Cu accumulation. We also demonstrate that cytosolic Cu accumulation inhibits S. aureus FeS enzymes.
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影响因子：
4.4
作者：
Baker, Jonathan;Sitthisak, Sutthirat;Morrissey, Julie A.
通讯作者：
Morrissey, Julie A.
影响因子：
4.1
作者：
Achard, Maud E. S.;Stafford, Sian L.;McEwan, Alastair G.
通讯作者：
McEwan, Alastair G.
DOI：
10.1038/nsb951
发表时间：
2003-08-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Glasfeld, A;Guedon, E;Brennan, RG
通讯作者：
Brennan, RG
影响因子：
11.3
作者：
Becker KW;Skaar EP
通讯作者：
Skaar EP
影响因子：
6.4
作者：
Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW