Elucidation of a novel Vibrio cholerae lipid A secondary hydroxy-acyltransferase and its role in innate immune recognition.
Elucidation of a novel Vibrio cholerae lipid A secondary hydroxy-acyltransferase and its role in innate immune recognition.
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DOI：
10.1111/j.1365-2958.2011.07765.x
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发表时间：
2011-09
影响因子：
3.6
通讯作者：
Trent MS
中科院分区：
文献类型：
--
作者：
Hankins JV;Madsen JA;Giles DK;Childers BM;Klose KE;Brodbelt JS;Trent MS
与大多数革兰氏阴性菌相似，霍乱弧菌外膜的外小叶由脂多糖组成。先前的报道提出，霍乱弧菌血清群O 1和O 139合成结构不同的脂质A结构域，其将脂多糖锚定在外膜内。在本研究中，通过质谱法分析了霍乱弧菌O 1和O 139的完整脂质A种类。我们证明与人类疾病相关的霍乱弧菌血清群合成类似的不对称六酰化脂质A物质，在2′-和3′-位置分别带有肉豆蔻酸酯（C14：0）和3-羟基月桂酸酯（3-OH C12：0）。我们实验室先前的报告表征了霍乱弧菌LpxL同系物Vc 0213，其将C14：0转移到葡萄糖胺二糖的2′-位。我们目前的研究结果将霍乱弧菌Vc 0212鉴定为一种新的脂质A二级羟基酰基转移酶，称为LpxN，负责将3-羟基月桂酸酯（3-OH C12：0）转移到霍乱弧菌脂质A结构域。重要的是，发现3′-连接的二级酰基链上存在3-羟基可促进霍乱弧菌的抗菌肽耐药性;然而，该官能团不是激活先天免疫应答所必需的。
Similar to most Gram-negative bacteria, the outer leaflet of the outer membrane of Vibrio cholerae is comprised of lipopolysaccharide. Previous reports have proposed that V. cholerae serogroups O1 and O139 synthesize structurally different lipid A domains, which anchor lipopolysaccharide within the outer membrane. In the current study, intact lipid A species of V. cholerae O1 and O139 were analysed by mass spectrometry. We demonstrate that V. cholerae serogroups associated with human disease synthesize a similar asymmetrical hexa-acylated lipid A species, bearing a myristate (C14:0) and 3-hydroxylaurate (3-OH C12:0) at the 2′- and 3′-positions respectively. A previous report from our laboratory characterized the V. cholerae LpxL homologue Vc0213, which transfers a C14:0 to the 2′-position of the glucosamine disaccharide. Our current findings identify V. cholerae Vc0212 as a novel lipid A secondary hydroxy-acyltransferase, termed LpxN, responsible for transferring the 3-hydroxylaurate (3-OH C12:0) to the V. cholerae lipid A domain. Importantly, the presence of a 3-hydroxyl group on the 3′-linked secondary acyl chain was found to promote antimicrobial peptide resistance in V. cholerae; however, this functional group was not required for activation of the innate immune response.
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DOI：
10.1073/pnas.0803281105
发表时间：
2008-06-24
影响因子：
11.1
作者：
Cameron, D. Ewen;Urbach, Jonathan M.;Mekalanos, John J.
通讯作者：
Mekalanos, John J.
影响因子：
3.6
作者：
Gibbons, HS;Kalb, SR;Raetz, CRH
通讯作者：
Raetz, CRH
DOI：
10.1016/0005-2760(74)90242-2
发表时间：
1974-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ARMSTRONG, IL;REDMOND, JW
通讯作者：
REDMOND, JW
影响因子：
3.2
作者：
GUZMAN, LM;BELIN, D;BECKWITH, J
通讯作者：
BECKWITH, J
影响因子：
4.8
作者：
Gibbons, HS;Lin, S;Raetz, CRH
通讯作者：
Raetz, CRH