Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection.

Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection.
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DOI:
10.1186/1471-2180-8-70
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发表时间:
2008-04-29
期刊:
影响因子:
4.2
通讯作者:
Nascimento AL
Nascimento AL
中科院分区:
生物学3区
文献类型:
--
作者:
Atzingen MV;Barbosa AS;De Brito T;Vasconcellos SA;de Morais ZM;Lima DM;Abreu PA;Nascimento AL

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在过去的几十年里,病原体与细胞外基质(ECM)的相互作用在宿主细胞的附着和侵袭中发挥了重要作用。与宿主组织的黏附是由微生物在感染过程中表达的暴露于表面的蛋白质介导的。致病性钩端螺旋体入侵和定植宿主的机制仍然知之甚少,因为几乎没有发现与该病发病有关的毒力因子。通过对问号钩端螺旋体的全基因组测序分析,可以鉴定出一系列可能的钩端螺旋体表面蛋白。在这里,我们报告了一种新的钩端螺旋体蛋白Lsa21(钩端螺旋体表面粘附素,21 kDa)的鉴定和特性。与其在黏附中的作用相一致,间接免疫荧光显示该蛋白被暴露在表面。LSA21与层粘连蛋白、IV型胶原和血浆纤维连接蛋白的结合具有特异性和剂量依赖性。层粘连蛋白被偏高碘酸钠氧化后,以浓度依赖的方式减少了蛋白质-层粘连蛋白的相互作用,这表明层粘连蛋白的糖基在这种相互作用中是至关重要的。Lsa21基因存在于问号钩端螺旋体的致病菌株中,但在腐生型双歧杆菌Patoc-1菌株中未发现。当致病菌株的培养减弱时,基因表达会丢失。渗透压、温度等环境因素在转录水平上影响Lsa21的表达。此外,抗Lsa21血清标记了人致死性钩端螺旋体病患者的肝和肾组织。我们的数据提示Lsa21在钩端螺旋体病的发病机制中起作用。
It has been well documented over past decades that interaction of pathogens with the extracellular matrix (ECM) plays a primary role in host cell attachment and invasion. Adherence to host tissues is mediated by surface-exposed proteins expressed by the microorganisms during infection. The mechanisms by which pathogenic leptospires invade and colonize the host remain poorly understood since few virulence factors contributing to the pathogenesis of the disease have been identified. Whole-genome sequencing analysis of L. interrogans allowed identification of a repertoire of putative leptospiral surface proteins. Here, we report the identification and characterization of a new leptospiral protein that exhibits extracellular matrix-binding properties, called as Lsa21 (leptospiral surface adhesin, 21 kDa). Compatible with its role in adhesion, the protein was shown to be surface-exposed by indirect immunofluorescence. Attachment of Lsa21 to laminin, collagen IV, and plasma fibronectin was specific and dose dependent. Laminin oxidation by sodium metaperiodate reduced the protein-laminin interaction in a concentration-dependent manner, indicating that laminin sugar moieties are crucial for this interaction. The gene coding for Lsa21 is present in pathogenic strains belonging to the L. interrogans species but was not found in the saprophytic L. biflexa serovar Patoc strain Patoc 1. Loss of gene expression occurs upon culture attenuation of pathogenic strains. Environmental factors such as osmolarity and temperature affect Lsa21 expression at the transcriptional level. Moreover, anti-Lsa21 serum labeled liver and kidney tissues of human fatal cases of leptospirosis. Our data suggest a role of Lsa21 in the pathogenesis of leptospirosis.
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DOI: 10.1016/j.bbrc.2007.07.196
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影响因子: 3.1
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影响因子: 5.6
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