Helicobacter pylori mutants defective in the clpP ATP-dependant protease and the chaperone clpA display reduced macrophage and murine survival
Helicobacter pylori mutants defective in the clpP ATP-dependant protease and the chaperone clpA display reduced macrophage and murine survival
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DOI：
10.1016/j.micpath.2008.10.004
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发表时间：
2009-01-01
影响因子：
3.8
通讯作者：
Jenks, Peter J.
中科院分区：
文献类型：
--
作者：
Loughlin, Michael F.;Arandhara, Victoria;Jenks, Peter J.
atp依赖的酪蛋白溶解蛋白酶（Clp）在抵抗环境胁迫、抗生素治疗和许多致病菌的宿主免疫防御中起重要作用。ClpP是蛋白水解亚基，而ClpA既作为伴侣，又作为atp酶，驱动受损或错误蛋白质的降解。胃病原体幽门螺杆菌感染了世界上大约一半的人口，可引起胃或十二指肠溃疡、胃恶性肿瘤和粘膜相关淋巴组织淋巴瘤。其体内环境的条件使生物体暴露于宿主免疫细胞和治疗后，抗生素，条件可能导致蛋白质损伤。我们在菌株SS1中产生了clpP和clpA的等基因非极性突变体和两个基因失活的双突变体。这些突变体对抗菌药物的敏感性增加，导致蛋白质损伤和/或氧化应激，此外还降低了人类巨噬细胞的存活率。在小鼠感染模型中，双突变体SS1 clpAP缺乏定植小鼠宿主的所有能力。这表明从蛋白质损伤中恢复的能力在这种生物体的发病机制中至关重要。英国皇家版权所有(c) 2008, Elsevier Ltd.出版版权所有。
The ATP-dependent caseinolytic proteases (Clp) are important in resistance against environmental stresses, antibiotic treatments and host immune defences for a number of pathogenic bacteria. ClpP is the proteolytic subunit, whilst ClpA acts both as a chaperone and as an ATPase driving the degradation of damaged or mis-made proteins. The gastric pathogen Helicobacter pylori infects approximately half of the world's population and can Cause gastric or duodenal ulcers, gastric malignancies and mucosa-associated lymphoid tissue lymphomas. The conditions of its in vivo environment expose the organism to host immune cells and upon treatment, antibiotics, conditions likely to cause protein damage. We generated isogenic nonpolar mutants in strain SS1 of clpP and clpA and double mutants with both genes inactivated. Such mutants showed increased sensitivity to antibacterials causing protein damage and/or oxidative stress, in addition to a reduced survival in human macrophages. In the mouse infection model the double mutant SS1 clpAP lacked all ability to colonize the murine host. This suggests that the ability to recover from protein damage is of key importance in the pathogenesis of this organism. Crown Copyright (c) 2008 Published by Elsevier Ltd. All rights reserved.