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雷本芳关于革兰氏阳性病原体中血红素获取与细菌致病机制的研究。

Benfang Lei's research on heme acquisition in Gram-positive pathogens and bacterial pathogenesis.

作者信息

Lei Benfang

机构信息

Benfang Lei, Department of Veterinary Molecular Biology, Montana State University, 960 Technology Blvd, Bozeman, MT 59717, United States.

出版信息

World J Biol Chem. 2010 Sep 26;1(9):286-90. doi: 10.4331/wjbc.v1.i9.286.

Abstract

Benfang Lei's laboratory conducts research on pathogenesis of human pathogen Group A Streptococcus (GAS) and horse pathogen Streptococcus equi (S. equi). His current research focuses on heme acquisition in Gram-positive pathogens and molecular mechanism of GAS and S. equi pathogenesis. Heme is an important source of essential iron for bacterial pathogens. Benfang Lei and colleagues identified the first cell surface heme-binding protein in Gram-positive pathogens and the heme acquisition system in GAS, demonstrated direct heme transfer from one protein to another, demonstrated an experimental pathway of heme acquisition by the Staphylococcus aureus Isd system, elucidated the activated heme transfer mechanism, and obtained evidence for a chemical mechanism of direct axial ligand displacement during the Shp-to-HtsA heme transfer reaction. These findings have considerably contributed to the progress that has been made over recent years in understanding the heme acquisition process in Gram-positive pathogens. Pathogenesis of GAS is mediated by an abundance of extracellular proteins, and pathogenic role and functional mechanism are not known for many of these virulence factors. Lei laboratory identified a secreted protein of GAS as a CovRS-regulated virulence factor that is a protective antigen and is critical for GAS spreading in the skin and systemic dissemination. These studies may lead to development of novel strategies to prevent and treat GAS infections.

摘要

雷本芳的实验室对人类病原体A群链球菌(GAS)和马病原体马链球菌(S. equi)的发病机制进行研究。他目前的研究重点是革兰氏阳性病原体中的血红素获取以及GAS和S. equi发病机制的分子机制。血红素是细菌病原体必需铁的重要来源。雷本芳及其同事在革兰氏阳性病原体中鉴定出首个细胞表面血红素结合蛋白以及GAS中的血红素获取系统,证明了血红素从一种蛋白直接转移到另一种蛋白,展示了金黄色葡萄球菌Isd系统获取血红素的实验途径,阐明了激活的血红素转移机制,并获得了Shp到HtsA血红素转移反应过程中直接轴向配体置换化学机制的证据。这些发现为近年来在理解革兰氏阳性病原体血红素获取过程方面取得的进展做出了重大贡献。GAS的发病机制由大量细胞外蛋白介导,其中许多毒力因子的致病作用和功能机制尚不清楚。雷实验室鉴定出一种GAS分泌蛋白是一种受CovRS调控的毒力因子,它是一种保护性抗原,对GAS在皮肤中的传播和全身扩散至关重要。这些研究可能会导致预防和治疗GAS感染新策略的开发。

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