Bactericidal Activity of Mouse α-Defensin Cryptdin-4 Predominantly Affects Noncommensal Bacteria
Bactericidal Activity of Mouse α-Defensin Cryptdin-4 Predominantly Affects Noncommensal Bacteria
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DOI：
10.1159/000322037
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发表时间：
2011-01-01
影响因子：
5.3
通讯作者：
Ayabe, Tokiyoshi
中科院分区：
文献类型：
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作者：
Masuda, Koji;Sakai, Naoki;Ayabe, Tokiyoshi
小鼠潘氏细胞α-防御素，称为cryptdins，分泌到肠腔中，具有杀微生物活性，并有助于肠道先天免疫。其中，Cryptdin-4（Crp 4）具有最强的杀微生物活性。在肠腔中，肠道细菌定殖并在宿主中引起有益作用。然而，Crp 4对肠道细菌的作用知之甚少。因此，我们研究了Crp 4对肠道细菌的杀菌活性，与非肠道细菌相比。氧化的Crp 4对12种肠道细菌中的8种仅显示出最小的杀菌活性或没有杀菌活性，包括两歧双歧杆菌和干酪乳杆菌。我们通过分析还原型Crp 4（r-Crp 4）进一步探讨了Crp 4保守二硫键的作用。r-Crp 4对12种细菌中的7种表现出比氧化Crp 4更强的杀菌活性。氧化型Crp 4和r-Crp 4对11种非肠道细菌中的11种（如沙门氏菌鼠伤寒血清型）和12种肠道细菌中的5种具有等效的杀菌活性。此外，当r-Crp 4暴露于cryptdins的加工酶，即MMP-7时，r-Crp 4被降解，杀菌活性消失。这些发现表明Crp 4对肠道微生物群具有选择性杀菌活性，并且活性依赖于二硫键。版权所有（C）2010 S. Karger AG，巴塞尔
Mouse Paneth cell alpha-defensins, termed cryptdins, are secreted into the intestinal lumen, have microbicidal activity, and contribute to intestinal innate immunity. Among them, cryptdin-4 (Crp4) has the most potent microbicidal activity. In the intestinal lumen, commensal bacteria colonize and elicit beneficial effects in the host. However, the effects of Crp4 against commensal bacteria are poorly understood. Thus, we investigated the bactericidal activities of Crp4 against commensal bacteria compared to noncommensal bacteria. Oxidized Crp4 showed only minimal or no bactericidal activity against 8 out of 12 commensal bacterial species, including Bifidobacterium bifidum and Lactobacillus Casei. We further addressed a role of the conserved disulfide bonds of Crp4 by analyzing reduced Crp4 (r-Crp4). r-Crp4 demonstrated significantly greater bactericidal activities against 7 of 12 commensal bacteria than did oxidized Crp4. Oxidized Crp4 and r-Crp4 elicited equivalently potent bactericidal activities against 11 of the 11 noncommensal bacteria tested, such as Salmonella enterica serovar Typhimurium, and against 5 of 12 commensal bacteria. Furthermore, when r-Crp4 was exposed to a processing enzyme of cryptdins, i.e. MMP-7, r-Crp4 was degraded and the bactericidal activities disappeared. These findings suggest that Crp4 has selective bactericidal activities against intestinal microbiota and that the activities are dependent on the disulfide bonds. Copyright (C) 2010 S. Karger AG, Basel