Apolipoprotein B48, the Structural Component of Chylomicrons, Is Sufficient to Antagonize Staphylococcus aureus Quorum-Sensing.
Apolipoprotein B48, the Structural Component of Chylomicrons, Is Sufficient to Antagonize Staphylococcus aureus Quorum-Sensing.
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DOI：
10.1371/journal.pone.0125027
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hall PR
中科院分区：
文献类型：
--
作者：
Elmore BO;Triplett KD;Hall PR
血清脂蛋白（LP）被越来越多地认为是一种双重用途的分子，既有助于胆固醇稳态又有助于宿主的先天防御。事实上，极低的脂蛋白水平与危重病人细菌感染的风险增加有关。在这方面，我们报道了载脂蛋白B100 (apoB100)，肝脏产生的极低密度脂蛋白（VLDL）的4536个氨基酸结构蛋白，限制了金黄色葡萄球菌的发病机制。金黄色葡萄球菌通过辅助基因调控子（agr）操纵子和自诱导肽（AIP）进行群体感应（QS），协调200多个毒力基因的表达。ApoB100通过结合和隔离分泌的AIP来阻止agr激活。重要的是，人血清LP不仅由肝脏产生，而且在摄取膳食脂质的过程中也由肠细胞以乳糜微粒的形式产生。与VLDL中的载脂蛋白100相反，人类肠细胞使用载脂蛋白48，载脂蛋白100的n端2152个氨基酸（48%）作为乳糜微粒的结构成分。有趣的是，危重患者的肠内喂养与感染并发症的风险降低有关，这表明当肝脏在急性期反应期间血清LP产生有限时，乳糜微粒可能有助于危重患者的宿主先天防御。因此，我们假设apoB48足以拮抗金黄色葡萄球菌QS。正如预期的那样，分离的apoB48-LP结合固定化AIP并拮抗agr信号。ApoB48-和apoB100-LP抑制agr活化的ic50分别为3.5 nM和2.3 nM，表明其具有保守的AIP结合位点。重要的是，在金黄色葡萄球菌感染的小鼠模型中，apoB48-LP拮抗QS，限制发病率并促进细菌清除。这项研究表明，两种天然形式的载脂蛋白B都可以拮抗金黄色葡萄球菌QS，并且可能提示乳糜微粒和肠细胞在宿主对金黄色葡萄球菌QS介导的发病机制的先天防御中以前未被认识到的作用。
Serum lipoproteins (LP) are increasingly being recognized as dual purpose molecules that contribute to both cholesterol homeostasis and host innate defense. In fact, very low LP levels are associated with increased risk of bacterial infection in critically ill patients. In this respect, we reported that apolipoprotein B100 (apoB100), the 4536 amino acid structural protein of very low density lipoprotein (VLDL) produced by the liver, limits Staphylococcus aureus pathogenesis. S. aureus uses quorum-sensing (QS) via the accessory gene regulator (agr) operon and an autoinducing peptide (AIP) to coordinate expression of over 200 virulence genes. ApoB100 prevents agr activation by binding and sequestering secreted AIP. Importantly, human serum LP are produced not only by the liver, but are also produced by enterocytes, in the form of chylomicrons, during uptake of dietary lipids. In contrast to apoB100 in VLDL, human enterocytes use apoB48, the N-terminal 2152 amino acids (48%) of apoB100, as the structural component of chylomicrons. Interestingly, enteral feeding of critically ill patients has been associated with decreased risk of infectious complications, suggesting chylomicrons could contribute to host innate defense in critically ill patients when serum LP production by the liver is limited during the acute phase response. Therefore, we hypothesized that apoB48 would be sufficient to antagonize S. aureus QS. As expected, isolated apoB48-LP bound immobilized AIP and antagonized agr-signaling. ApoB48- and apoB100-LP inhibited agr activation with IC50s of 3.5 and 2.3 nM, respectively, demonstrating a conserved AIP binding site. Importantly, apoB48-LP antagonized QS, limited morbidity and promoted bacterial clearance in a mouse model of S. aureus infection. This work demonstrates that both naturally occurring forms of apolipoprotein B can antagonize S. aureus QS, and may suggest a previously unrecognized role for chylomicrons and enterocytes in host innate defense against S. aureus QS-mediated pathogenesis.
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DOI：
10.1097/ta.0b013e3182826be0
发表时间：
2013-04
期刊：
The journal of trauma and acute care surgery
影响因子：
--
作者：
Femling JK;West SD;Hauswald EK;Gresham HD;Hall PR
通讯作者：
Hall PR
影响因子：
15.9
作者：
HARRIS, HW;GRUNFELD, C;RAPP, JH
通讯作者：
RAPP, JH
影响因子：
6.7
作者：
Hall PR;Elmore BO;Spang CH;Alexander SM;Manifold-Wheeler BC;Castleman MJ;Daly SM;Peterson MM;Sully EK;Femling JK;Otto M;Horswill AR;Timmins GS;Gresham HD
通讯作者：
Gresham HD
影响因子：
5.2
作者：
BRAUNER, E;GORBACH, S;DAVEY, P
通讯作者：
DAVEY, P
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影响因子：
--
作者：
Han, Cong;Lin, Yahui;Wang, Heng
通讯作者：
Wang, Heng