Outer membrane permeabilization is an essential step in the killing of gram-negative bacteria by the lectin RegIIIβ.
Outer membrane permeabilization is an essential step in the killing of gram-negative bacteria by the lectin RegIIIβ.
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DOI：
10.1371/journal.pone.0069901
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hardt WD
中科院分区：
文献类型：
--
作者：
Miki T;Hardt WD
C型凝集素RegIIIβ可杀灭某些革兰氏阳性菌和革兰氏阴性菌。S.鼠伤寒沙门氏菌依赖于细菌生长阶段，即，对数生长期的细菌结合RegIIIβ，随后被杀死。脂质A是RegIIIβ的细菌靶标之一。然而，在分子水平上，尚不清楚RegIIIβ如何与革兰氏阴性菌相互作用并杀死革兰氏阴性菌。在这里，我们表明RegIIIβ与革兰氏阴性菌在两个不同的步骤中相互作用。最初，它与表面暴露的脂质A结合。脂多糖（LPS）的O-抗原可以屏蔽脂质A，如wbaP突变体对RegIIIβ介导的杀伤的敏感性所示。与抗脂质A抗体孵育后细胞活力增加也支持这一结论。这种RegIIIβ-结合使外膜透化到疏水性染料如溴化铵或大体积溶菌酶如溶菌酶。相反，温和去污剂Triton X-100破坏外膜完整性可增强RegIIIβ的抗菌作用。根据我们的观察，我们得出结论，RegIIIβ与革兰氏阴性菌在两个后续步骤中相互作用。最初，它与外膜结合，从而导致外膜透化。这个初始步骤对于RegIIIβ到达第二个仍然不太清楚的靶位点（可能位于周质或细胞质膜中）是必要的，从而触发细菌死亡。这为RegIIIβ杀菌机制的外膜步骤提供了新的见解。
The C-type lectin RegIIIβ can kill certain Gram-positive and Gram-negative bacteria. The susceptibility of S. Typhimurium depends on the bacterial growth phase, i.e., bacteria from the logarithmic growth phase do bind RegIIIβ and are subsequently killed. Lipid A is one of the bacterial targets for RegIIIβ. However, at the molecular level, it is not understood how RegIIIβ interacts with and kills Gram-negative bacteria. Here, we show that RegIIIβ interacts with Gram-negative bacteria in two distinct steps. Initially, it binds to surface-exposed lipid A. The lipid A can be shielded by the O-antigen of lipopolysaccharide (LPS), as indicated by the exquisite susceptibility of wbaP mutants to RegIIIβ-mediated killing. Increased cell viability after incubation with an anti-lipid A antibody also supports this conclusion. This RegIIIβ-binding permeabilizes the outer membrane to hydrophobic dyes like Ethidium bromide or to bulky bacteriolytic enzymes like lysozyme. Conversely, compromising the outer membrane integrity by the mild detergent Triton X-100 enhances the antibacterial effect of RegIIIβ. Based on our observations, we conclude that RegIIIβ interacts with Gram-negative bacteria in two subsequent steps. Initially, it binds to the outer membrane thus leading to outer membrane permeabilization. This initial step is necessary for RegIIIβ to reach a second, still not well understood target site (presumably localized in the periplasm or the cytoplasmic membrane), thereby triggering bacterial death. This provides novel insights into the outer membrane-step of the bactericidal mechanism of RegIIIβ.
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沙门氏菌诱导的粘膜凝集素regiiiβ杀死了竞争性肠道菌群。
影响因子：
3.7
作者：
Stelter C;Käppeli R;König C;Krah A;Hardt WD;Stecher B;Bumann D
通讯作者：
Bumann D
影响因子：
3.5
作者：
Narushima, Y;Unno, M;Okamoto, H
通讯作者：
Okamoto, H
影响因子：
3.1
作者：
Ilg, Karin;Endt, Kathrin;Hardt, Wolf-Dietrich
通讯作者：
Hardt, Wolf-Dietrich
DOI：
10.1073/pnas.0808723105
发表时间：
2008-12-30
影响因子：
11.1
作者：
Vaishnava, Shipra;Behrendt, Cassie L.;Hooper, Lora V.
通讯作者：
Hooper, Lora V.
影响因子：
3.3
作者：
ROSENTHAL, KS;STORM, DR
通讯作者：
STORM, DR