A Helicobacter pylori Homolog of Eukaryotic Flotillin Is Involved in Cholesterol Accumulation, Epithelial Cell Responses and Host Colonization.
A Helicobacter pylori Homolog of Eukaryotic Flotillin Is Involved in Cholesterol Accumulation, Epithelial Cell Responses and Host Colonization.
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DOI：
10.3389/fcimb.2017.00219
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发表时间：
2017
影响因子：
5.7
通讯作者：
Ferrero RL
中科院分区：
文献类型：
--
作者：
Hutton ML;D'Costa K;Rossiter AE;Wang L;Turner L;Steer DL;Masters SL;Croker BA;Kaparakis-Liaskos M;Ferrero RL
人类病原体幽门螺杆菌从真核细胞中的膜筏结构域（通常称为“脂筏”）获得胆固醇。将这种胆固醇掺入到H.幽门螺杆菌的细胞膜允许细菌避免宿主免疫系统的清除，并抵抗抗生素和抗微生物肽的作用。胆固醇在H. pylori细菌表明，这种病原体可能在其膜内具有胆固醇富集结构域。与这个建议相一致，我们确定了一个假设的H。pylori蛋白（HP 0248），其与通常在真核细胞的胆固醇富集结构域中发现的flotillin蛋白具有同源性。如真核细胞flotillin蛋白所示，HP 0248在耐洗涤剂的H.幽门。重要的是，H。pylori HP 0248突变株的胆固醇水平低于野生型（P < 0.01）。HP 0248突变体细菌还表现出IV型分泌功能的缺陷，如上皮细胞中降低的IL-8应答和CagA易位所示（P < 0.05），并且与野生型细菌相比，在小鼠中建立慢性感染的能力较低（P < 0.05）。因此，我们确定了一个H。pylori flotillin蛋白，并显示其对细菌毒力的重要性。综上所述，数据表明H. pylori flotillin在宿主-病原体相互作用中的作用。我们建议H.幽门螺旋杆菌漂浮蛋白可能是该病原体中毒力蛋白组织成膜筏样结构所必需的。
The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as “lipid rafts.” Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H. pylori protein (HP0248) with homology to the flotillin proteins normally found in the cholesterol-enriched domains of eukaryotic cells. As shown for eukaryotic flotillin proteins, HP0248 was detected in detergent-resistant membrane fractions of H. pylori. Importantly, H. pylori HP0248 mutants contained lower levels of cholesterol than wild-type bacteria (P < 0.01). HP0248 mutant bacteria also exhibited defects in type IV secretion functions, as indicated by reduced IL-8 responses and CagA translocation in epithelial cells (P < 0.05), and were less able to establish a chronic infection in mice than wild-type bacteria (P < 0.05). Thus, we have identified an H. pylori flotillin protein and shown its importance for bacterial virulence. Taken together, the data demonstrate important roles for H. pylori flotillin in host-pathogen interactions. We propose that H. pylori flotillin may be required for the organization of virulence proteins into membrane raft-like structures in this pathogen.