The determination of antibacterial mode for cationic lipopeptides brevibacillins against Salmonella typhimurium by quantum chemistry calculation
The determination of antibacterial mode for cationic lipopeptides brevibacillins against Salmonella typhimurium by quantum chemistry calculation
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量子化学计算确定阳离子脂肽短杆菌素对鼠伤寒沙门氏菌的抗菌模式
DOI：
10.1007/s00253-021-11398-5
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发表时间：
2021-06
影响因子：
5
通讯作者：
Lu Yingjian
中科院分区：
文献类型：
--
作者：
Wu Yubo;Nie Ting;Meng Fanqiang;Zhou Libang;Chen Meirong;Sun Jing;Lu Zhaoxin;Lu Yingjian
短杆菌素是由侧孢短杆菌 fmb70 CGMCC 18426 产生的广谱阳离子抗菌脂肽。本研究通过量子化学计算研究了短杆菌素对鼠伤寒沙门氏菌 CICC 21493 的抗菌模式。 LPS、Mg2+和Ca2+的添加部分降低了短杆西林和短杆西林V对鼠伤寒沙门氏菌的抗菌活性，这表明这两种阳离子脂肽可以与LPS结合并置换LPS网络上的二价阳离子。短杆菌和短杆菌V从鼠伤寒沙门氏菌中释放LPS导致致密的LPS网络被破坏并增加了外膜的通透性。量子化学计算分析表明，Lys7是破坏外膜最关键的氨基酸残基。三个质子化氨基（Orn3-NH3、Lys7-NH3 和 Lys10-NH3）的总平均 N-H 电荷差异决定了 brevibacillin V 结合 LPS 的能力强于 brevibacillin。钙黄绿素从脂质体完全渗漏以及DiSC3-5从细胞质膜(CM)释放表明短杆菌素和短杆菌素V可能破坏CM。短杆菌西林和短杆菌西林V通过膜损伤发挥抗菌活性，其中高浓度64-256μg/mL的OM渗透性和低浓度4μg/mL的CM膜损伤。我们的发现可能有助于了解阳离子脂肽的广谱抗菌机制并设计新型抗菌肽。要点： • 短杆菌西林 V 对 LPS 的亲和力比短杆菌西林更强。 • N-H 电荷差异是 LPS 亲和力差异的关键。 • 短杆菌素通过置换LPS 上的二价阳离子来抑制沙门氏菌。
Brevibacillins are broad-spectrum cationic antimicrobial lipopeptides produced by Brevibacillus laterosporus fmb70 CGMCC 18426. The antibacterial mode of brevibacillins against Salmonella typhimurium CICC 21493 was investigated by quantum chemistry calculation in this study. The addition of LPS, Mg2+, and Ca2+partially reduced the antimicrobial activity of brevibacillin and brevibacillin V against S. typhimurium, which indicated that the two cationic lipopeptides could bind to LPS and displaced the divalent cations on the LPS network. Release of LPS from S. typhimurium by brevibacillin and brevibacillin V resulted in destroying the dense LPS network and increasing the permeability of the outer membrane. Quantum chemistry calculation analysis revealed that Lys7 is the most critical amino acid residue to destroy the outer membrane. The total average N-H charge difference of the three protonated amino groups (Orn3-NH3, Lys7-NH3, and Lys10-NH3) determined the ability of brevibacillin V to bind LPS stronger than brevibacillin. Calcein complete leakage from liposomes and release of DiSC3-5 from the cytoplasmic membrane (CM) indicated that brevibacillin and brevibacillin V may destroy the CM. Brevibacillin and brevibacillin V exhibited their antimicrobial activities through membrane damages, where the OM permeability with high concentration of 64-256 µg/mL and membrane damage of CM with a low concentration of 4 μg/mL. Our finding might be helpful to understand the broad-spectrum antimicrobial mechanism of cationic lipopeptide and to design the novel antimicrobial peptide. KEY POINTS: • Brevibacillin V had stronger affinity for LPS than brevibacillin. • The N-H charge difference was the key of the difference in the affinity to LPS. • Brevibacillins inhibited Salmonella by displacing the divalent cations on the LPS.
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影响因子：
--
作者：
Khan MF;Nahar N;Rashid RB;Chowdhury A;Rashid MA
通讯作者：
Rashid MA
DOI：
10.1016/j.saa.2018.01.045
发表时间：
2018-04
期刊：
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
影响因子：
--
作者：
N. Machado;B. G. Carvalho;C. A. T. Soto;A. Martin;P. Fávero
通讯作者：
N. Machado;B. G. Carvalho;C. A. T. Soto;A. Martin;P. Fávero
影响因子：
3.4
作者：
Lin Yang;T. Harroun;William T. Heller;Thomas M. Weiss;Huey W. Huang
通讯作者：
Lin Yang;T. Harroun;William T. Heller;Thomas M. Weiss;Huey W. Huang
影响因子：
11.1
作者：
J. Crump;S. Luby;E. Mintz
通讯作者：
J. Crump;S. Luby;E. Mintz
DOI：
10.1007/978-3-642-74095-4_1
发表时间：
1989
期刊：
--
影响因子：
--
作者：
H. Nikaido
通讯作者：
H. Nikaido