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结核分枝杆菌 PE/PPE 家族抗原的表达和调控网络。

Expression and regulatory networks of Mycobacterium tuberculosis PE/PPE family antigens.

机构信息

Key Laboratory of Regional Characteristic Agricultural Resources, College of Life Sciences, Neijiang Normal University, Neijiang, China.

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

出版信息

J Cell Physiol. 2019 Jun;234(6):7742-7751. doi: 10.1002/jcp.27608. Epub 2018 Nov 27.

Abstract

PE/PPE family antigens are distributed mainly in pathogenic mycobacteria and serve as potential antituberculosis (TB) vaccine components. Some PE/PPE family antigens can regulate the host innate immune response, interfere with macrophage activation and phagolysosome fusion, and serve as major sources of antigenic variation. PE/PPE antigens have been associated with mycobacteria pathogenesis; pe/ppe genes are mainly found in pathogenic mycobacteria and are differentially expressed between Mtb and Mycobacterium bovis. PE/PPE proteins were essential for the growth of Mtb, and PE/PPE proteins were differentially expressed under a variety of conditions. Multiple mycobacterial-virulence-related transcription factors, sigma factors, the global transcriptional regulation factor Lsr2, MprAB, and PhoPR two-component regulatory systems, and cyclic adenine monophosphate-dependent regulators, regulate the expression of PE/PPE family antigens. Multiple-scale integrative analysis revealed the expression and regulatory networks of PE/PPE family antigens underlying the virulence and pathogenesis of Mtb, providing important clues for the discovery of new anti-TB measures.

摘要

PE/PPE 家族抗原主要分布在致病性分枝杆菌中,可作为潜在的抗结核(TB)疫苗成分。一些 PE/PPE 家族抗原可以调节宿主固有免疫反应,干扰巨噬细胞的激活和吞噬溶酶体融合,并作为抗原变异的主要来源。PE/PPE 抗原与分枝杆菌的发病机制有关;pe/ppe 基因主要存在于致病性分枝杆菌中,并且在结核分枝杆菌和牛分枝杆菌之间存在差异表达。PE/PPE 蛋白对于 Mtb 的生长是必需的,并且在多种条件下差异表达。多种分枝杆菌毒力相关转录因子、σ因子、全局转录调控因子 Lsr2、MprAB 和 PhoPR 双组分调节系统以及环磷酸腺苷依赖性调节因子调节 PE/PPE 家族抗原的表达。多尺度综合分析揭示了 Mtb 毒力和发病机制中 PE/PPE 家族抗原的表达和调控网络,为发现新的抗结核措施提供了重要线索。

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