Mechanisms of immune evasion by Mycobacterium tuberculosis: the impact of T7SS and cell wall lipids on host defenses.

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2024-10-01 Epub Date: 2024-10-08 DOI:10.1080/10409238.2024.2411264
Asrar Ahmad Malik, Mohd Shariq, Javaid Ahmad Sheikh, Udyeshita Jaiswal, Haleema Fayaz, Gauri Shrivastava, Nasreen Z Ehtesham, Seyed E Hasnain
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Abstract

Mycobacterium tuberculosis (M. tb) is one of the most successful human pathogens, causing a severe and widespread infectious disease. The frequent emergence of multidrug-resistant (MDR) strains has exacerbated this public health crisis, particularly in underdeveloped regions. M. tb employs a sophisticated array of virulence factors to subvert host immune responses, both innate and adaptive. It utilizes the early secretory antigenic target (ESAT6) secretion system 1 (ESX-1) type VII secretion system (T7SS) and cell wall lipids to disrupt phagosomal integrity, inhibiting phagosome maturation, and fusion with lysosomes. Although host cells activate mechanisms such as ubiquitin (Ub), Ub-ligase, and cyclic GMP-AMP synthase-stimulator of interferon genes 1 (CGAS-STING1)-mediated autophagy to inhibit M. tb survival within macrophages, the pathogen counteracts these defenses with its own virulence factors, thereby inhibiting autophagy and dampening host-directed responses. T7SSs are critical for transporting proteins across the complex mycobacterial cell envelope, performing essential functions, including metabolite uptake, immune evasion, and conjugation. T7SS substrates fall into two main families: ESAT-6 system proteins, which are found in both Firmicutes and Actinobacteria, and proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) proteins, which are unique to mycobacteria. Recent studies have highlighted the significance of T7SSs in mycobacterial growth, virulence, and pathogenesis. Understanding the mechanisms governing T7SSs could pave the way for novel therapeutic strategies to combat mycobacterial diseases, including tuberculosis (TB).

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结核分枝杆菌逃避免疫的机制:T7SS 和细胞壁脂质对宿主防御的影响。
结核分枝杆菌(M. tb)是最成功的人类病原体之一,可引起严重而广泛的传染病。耐多药(MDR)菌株的频繁出现加剧了这一公共卫生危机,尤其是在欠发达地区。结核杆菌利用一系列复杂的毒力因子来破坏宿主的先天性和适应性免疫反应。它利用早期分泌抗原靶标(ESAT6)分泌系统 1(ESX-1)VII 型分泌系统(T7SS)和细胞壁脂质破坏吞噬体的完整性,抑制吞噬体的成熟以及与溶酶体的融合。虽然宿主细胞会激活泛素(Ub)、Ub 连接酶和环 GMP-AMP 合成酶-干扰素基因 1(CGAS-STING1)介导的自噬等机制来抑制 M. tb 在巨噬细胞内的存活,但病原体会用自身的毒力因子来抵消这些防御措施,从而抑制自噬并抑制宿主定向反应。T7SS 对于在复杂的分枝杆菌细胞包膜上转运蛋白质至关重要,可发挥重要功能,包括代谢物吸收、免疫逃避和连接。T7SS 底物分为两大类:ESAT-6 系统蛋白存在于固氮菌和放线菌中,而脯氨酸-谷氨酸(PE)和脯氨酸-脯氨酸-谷氨酸(PPE)蛋白则是分枝杆菌所特有的。最近的研究强调了 T7SS 在分枝杆菌生长、毒力和致病过程中的重要作用。了解 T7SSs 的作用机制可为制定新型治疗策略以防治包括结核病在内的分枝杆菌疾病铺平道路。
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来源期刊
CiteScore
14.90
自引率
0.00%
发文量
6
期刊介绍: As the discipline of biochemistry and molecular biology have greatly advanced in the last quarter century, significant contributions have been made towards the advancement of general medicine, genetics, immunology, developmental biology, and biophysics. Investigators in a wide range of disciplines increasingly require an appreciation of the significance of current biochemical and molecular biology advances while, members of the biochemical and molecular biology community itself seek concise information on advances in areas remote from their own specialties. Critical Reviews in Biochemistry and Molecular Biology believes that well-written review articles prove an effective device for the integration and meaningful comprehension of vast, often contradictory, literature. Review articles also provide an opportunity for creative scholarship by synthesizing known facts, fruitful hypotheses, and new concepts. Accordingly, Critical Reviews in Biochemistry and Molecular Biology publishes high-quality reviews that organize, evaluate, and present the current status of high-impact, current issues in the area of biochemistry and molecular biology. Topics are selected on the advice of an advisory board of outstanding scientists, who also suggest authors of special competence. The topics chosen are sufficiently broad to interest a wide audience of readers, yet focused enough to be within the competence of a single author. Authors are chosen based on their activity in the field and their proven ability to produce a well-written publication.
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