Curcumin activation of a bacterial mechanosensitive channel underlies its membrane permeability and adjuvant properties.
Curcumin activation of a bacterial mechanosensitive channel underlies its membrane permeability and adjuvant properties.
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DOI：
10.1371/journal.ppat.1010198
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发表时间：
2021-12
期刊：
影响因子：
6.7
通讯作者：
Blount P
中科院分区：
文献类型：
--
作者：
Wray R;Iscla I;Blount P
姜黄素是一种从姜黄根茎中分离出来的天然化合物，已被证明具有抗菌特性。它对细菌具有几种生理作用，包括涉及RecA的类骨化反应，膜透化，抑制分隔，并且它还可以与其他抗生素协同作用。姜黄素透化细菌膜的机制尚不清楚。大多数细菌物种含有大电导率的机械敏感通道MscL，其起到生物紧急释放阀的作用;这些大孔通道响应于来自渗透压变化的膜张力而打开，并且为了避免细胞裂解，允许溶质从细胞质中释放。在这里，我们表明，MscL通道的膜透化姜黄素以及其与其他抗生素的协同特性的基础上，通过允许抗生素进入细胞质; MscL似乎也有抑制作用，分隔，这是增强时，激活姜黄素。姜黄的根茎含有一种叫做姜黄素的化合物，它已被证明具有多种生物活性，包括抗菌特性。先前的研究发现，姜黄素处理后，细菌细胞变得“渗漏”;它们的膜透化。此外，姜黄素似乎与其他几种抗生素协同作用。最后，已经观察到姜黄素可以导致细菌细胞生长但不能分裂，从而导致具有多个DNA拷贝的长丝状细胞。但这些发现背后的机制是神秘的。在这里，我们表明姜黄素靶向细菌细胞包膜中的一种特定蛋白质，这种蛋白质可以打开一个非常大的孔--生物界已知的最大的调节孔。这个孔通常仅在极端情况下用作“紧急释放阀”，防止渗透应力导致的溶解。正是姜黄素不适当地打开了这个孔，导致细菌细胞包膜的渗透，以及与其他抗生素的协同作用，使抗生素更容易进入细胞内部，甚至抑制细菌细胞分裂。
Curcumin, a natural compound isolated from the rhizome of turmeric, has been shown to have antibacterial properties. It has several physiological effects on bacteria including an apoptosis-like response involving RecA, membrane permeabilization, inhibiting septation, and it can also work synergistically with other antibiotics. The mechanism by which curcumin permeabilizes the bacterial membrane has been unclear. Most bacterial species contain a Mechanosensitive channel of large conductance, MscL, which serves the function of a biological emergency release valve; these large-pore channels open in response to membrane tension from osmotic shifts and, to avoid cell lysis, allow the release of solutes from the cytoplasm. Here we show that the MscL channel underlies the membrane permeabilization by curcumin as well as its synergistic properties with other antibiotics, by allowing access of antibiotics to the cytoplasm; MscL also appears to have an inhibitory role in septation, which is enhanced when activated by curcumin. The rhizome of turmeric contains a compound, called curcumin, which has been shown to have several biological activities, including antibacterial properties. Previous studies have found that upon curcumin treatment, bacterial cells become “leaky”; their membranes permeabilized. In addition, curcumin appears to work in synergy with several other antibiotics. Finally, it has been observed that curcumin can lead to bacterial cells that can grow but not divide, thus leading to long filamentous cells with multiple copies of their DNA. But the mechanisms underlying these findings were mysterious. Here we show that curcumin targets a specific protein in the bacterial cell envelope that can open a very large pore—the largest regulated pore known in the biological world. This pore usually is only used in extreme situations as an “emergency release valve” that prevents lysis from osmotic stresses. It is the inappropriate opening of this pore by curcumin that leads to the permeation of the bacterial cell envelope, as well as the synergy with other antibiotics by allowing the antibiotics easier access to the inside of the cell, and even the inhibition of bacterial cell division.
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影响因子：
3.7
作者：
Iscla, Irene;Wray, Robin;Blount, Paul
通讯作者：
Blount, Paul
影响因子：
2.9
作者：
Kamaraju, Kishore;Sukharev, Sergei
通讯作者：
Sukharev, Sergei
DOI：
10.1007/978-1-60327-360-2_16
发表时间：
2010-01-01
期刊：
LIPOSOMES: METHODS AND PROTOCOLS, VOL 1
影响因子：
--
作者：
Kocer, Armagan
通讯作者：
Kocer, Armagan
DOI：
10.1007/s00249-005-0468-x
发表时间：
2005-07-01
影响因子：
2
作者：
Nguyen, T;Clare, B;Martinac, B
通讯作者：
Martinac, B
影响因子：
7.3
作者：
Nelson KM;Dahlin JL;Bisson J;Graham J;Pauli GF;Walters MA
通讯作者：
Walters MA