Quinone Pool, a Key Target of Plant Flavonoids Inhibiting Gram-Positive Bacteria.
Quinone Pool, a Key Target of Plant Flavonoids Inhibiting Gram-Positive Bacteria.
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DOI：
10.3390/molecules28134972
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发表时间：
2023-06-24
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影响因子：
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植物黄酮类化合物作为新型抗菌剂或佐剂越来越受到人们的关注。我们前期的工作证实，细胞膜是植物黄酮类化合物作用于革兰氏阳性菌的主要部位，可能与呼吸链的抑制有关。受植物黄酮与氢甲基萘醌（MKH2）相似的结构和抗氧化特性的启发，我们推断醌库可能是植物黄酮抑制革兰氏阳性菌的关键靶点。为了验证这一点，初步筛选了6种结构亚型的12种植物黄酮类化合物，并根据植物黄酮类化合物对革兰氏阳性菌的抗菌定量关系预测了它们对革兰氏阳性菌的最低抑菌浓度（MIC）。结果表明它们具有不同的抗菌活性。采用肉汤微量稀释法测定其对金黄色葡萄球菌的 MIC 后，最终筛选出 9 种 MIC 范围为 2 至 4096 μg/mL 或大于 1024 μg/mL 的化合物，然后测定其对金黄色葡萄球菌的 MIC，并干扰不同浓度的甲基萘醌−4 (MK−4) 和从金黄色葡萄球菌中提取的 MK。结果表明，植物黄酮类化合物的抗菌活性越大，随着MK−4（2～256 μg/mL）和MK提取物（4～512 μg/mL）干扰浓度的增加，其抗菌活性下降幅度越大，而MIC等于或大于512 μg/mL的则略有下降或保持不变。特别是，在MK−4（256 μg/mL）和MK提取物（512 μg/mL）的干扰下，这12种植物黄酮中对金黄色葡萄球菌抑制活性最强的α-山竹素的MIC分别增加了16倍和8至16倍。综上所述，提出醌库是植物黄酮类化合物抑制革兰氏阳性菌的关键靶点，可能涉及多种酶和非酶抑制机制。
Plant flavonoids have attracted increasing attention as new antimicrobial agents or adjuvants. In our previous work, it was confirmed that the cell membrane is the major site of plant flavonoids acting on the Gram-positive bacteria, which likely involves the inhibition of the respiratory chain. Inspired by the similar structural and antioxidant characters of plant flavonoids to hydro-menaquinone (MKH2), we deduced that the quinone pool is probably a key target of plant flavonoids inhibiting Gram-positive bacteria. To verify this, twelve plant flavonoids with six structural subtypes were preliminarily selected, and their minimum inhibitory concentrations (MICs) against Gram-positive bacteria were predicted from the antimicrobial quantitative relationship of plant flavonoids to Gram-positive bacteria. The results showed they have different antimicrobial activities. After their MICs against Staphylococcus aureus were determined using the broth microdilution method, nine compounds with MICs ranging from 2 to 4096 μg/mL or more than 1024 μg/mL were eventually selected, and then their MICs against S. aureus were determined interfered with different concentrations of menaquinone−4 (MK−4) and the MKs extracted from S. aureus. The results showed that the greater the antibacterial activities of plant flavonoids were, the more greatly their antibacterial activities decreased along with the increase in the interfering concentrations of MK−4 (from 2 to 256 μg/mL) and the MK extract (from 4 to 512 μg/mL), while those with the MICs equal to or more than 512 μg/mL decreased a little or remained unchanged. In particular, under the interference of MK−4 (256 μg/mL) and the MK extract (512 μg/mL), the MICs of α-mangostin, a compound with the greatest inhibitory activity to S. aureus out of these twelve plant flavonoids, increased by 16 times and 8 to 16 times, respectively. Based on the above, it was proposed that the quinone pool is a key target of plant flavonoids inhibiting Gram-positive bacteria, and which likely involves multiple mechanisms including some enzyme and non-enzyme inhibitions.
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影响因子：
5.6
作者：
Song, Lianyu;Hu, Xin;Ren, Xiaomin;Liu, Jing;Liu, Xiaoye
通讯作者：
Liu, Xiaoye
DOI：
10.1002/advs.202100749
发表时间：
2021-08
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
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作者：
Song M;Liu Y;Li T;Liu X;Hao Z;Ding S;Panichayupakaranant P;Zhu K;Shen J
通讯作者：
Shen J
基于HPLC-UV技术的甲萘醌生产菌株的化学筛选方法
影响因子：
2.2
作者：
Cao, Sheng;Du, Xia;Kuang, Bingdi
通讯作者：
Kuang, Bingdi
DOI：
10.3390/molecules27041149
发表时间：
2022-02-09
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Shamsudin NF;Ahmed QU;Mahmood S;Ali Shah SA;Khatib A;Mukhtar S;Alsharif MA;Parveen H;Zakaria ZA
通讯作者：
Zakaria ZA
DOI：
10.1016/s0140-6736(21)02724-0
发表时间：
2022-02-12
期刊：
Lancet (London, England)
影响因子：
--
作者：
Antimicrobial Resistance Collaborators
通讯作者：
Antimicrobial Resistance Collaborators