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PE 蛋白家族在分枝杆菌毒力中的作用:抗结核疫苗和药物设计的潜力。

Role of PE family of proteins in mycobacterial virulence: Potential on anti-TB vaccine and drug design.

作者信息

Dahiya Priyanka, Bisht Manoj Kumar, Mukhopadhyay Sangita

机构信息

Laboratory of Molecular Cell Biology, BRIC-Center for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India.

Graduate Studies, Regional Center for Biotechnology, Faridabad, Haryana, India.

出版信息

Int Rev Immunol. 2025;44(4):213-228. doi: 10.1080/08830185.2025.2455161. Epub 2025 Jan 31.

Abstract

Macrophages are the primary targets of mycobacterial infection, which plays crucial roles both in nonspecific defence (innate immunity) as well as specific defence mechanisms (adaptive immunity) by secreting various cytokines, antimicrobial mediators and presenting antigens to T-cells. Sequencing of the mycobacterial genome revealed that 10% of its coding ability is devoted to the Pro-Glu motif-containing (PE) and Pro-Pro-Glu motif-containing (PPE) family proteins. While the function of most of the genes belonging to the PE-PPE family initially remained unannotated, recent studies have shown that many proteins of this family play critical roles in bacterial growth and cell functions, and manipulation of host immune responses, indicating their potential roles in mycobacterial virulence. In this review, we have focussed on describing the immunological importance of particularly the PE group of proteins in the context of 'virulence' determinants and outcome of tuberculosis disease. Additionally, we have discussed about the roles of these proteins on host-pathogen-interaction and how some of these genes can be targeted which may help us in designing effective anti-TB therapeutics.

摘要

巨噬细胞是分枝杆菌感染的主要靶标,它通过分泌各种细胞因子、抗菌介质以及向T细胞呈递抗原,在非特异性防御(固有免疫)和特异性防御机制(适应性免疫)中均发挥着关键作用。分枝杆菌基因组测序显示,其10%的编码能力用于含脯氨酸-谷氨酸基序(PE)和含脯氨酸-脯氨酸-谷氨酸基序(PPE)的家族蛋白。虽然最初属于PE-PPE家族的大多数基因的功能仍未得到注释,但最近的研究表明,该家族的许多蛋白在细菌生长、细胞功能以及宿主免疫反应调控中发挥着关键作用,表明它们在分枝杆菌毒力中具有潜在作用。在本综述中,我们重点描述了特别是PE组蛋白在“毒力”决定因素和结核病病情转归背景下的免疫学重要性。此外,我们还讨论了这些蛋白在宿主-病原体相互作用中的作用,以及如何靶向其中一些基因,这可能有助于我们设计有效的抗结核治疗方法。

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