Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target.
Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target.
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DOI：
10.1017/s0031182016002377
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发表时间：
2018-03
期刊：
影响因子：
2.4
通讯作者：
Besra GS
中科院分区：
文献类型：
--
作者：
Abrahams KA;Besra GS
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）是结核病的病原体，被世界卫生组织列为全球性的卫生紧急事件。沿着每年超过100万人的死亡，以及Mtb的多重和广泛耐药菌株的出现，已经引发了对这种微生物的致病性和生物化学的深入研究，指导了抗TB化学治疗剂的开发。基本的分枝杆菌细胞壁，与所有细菌共享一些共同的特征，代表了一个明显的“阿喀琉斯之踵”，自从结核病治疗出现以来，结核病化疗一直针对它。这种复杂的结构由三个不同的层组成，肽聚糖，阿拉伯半乳聚糖和分枝菌酸，在支持细胞生长，毒力和提供抗生素屏障方面至关重要。细胞壁合成和组装的基本性质使得分枝杆菌细胞壁成为抗TB药物最广泛开发的靶标。本文综述了主要细胞壁组分的生物合成，突出了现有临床药物的抑制机制，并说明了其他未开发的酶作为未来药物靶点的潜力。
Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB), is recognized as a global health emergency as promoted by the World Health Organization. Over 1 million deaths per year, along with the emergence of multi- and extensively-drug resistant strains of Mtb, have triggered intensive research into the pathogenicity and biochemistry of this microorganism, guiding the development of anti-TB chemotherapeutic agents. The essential mycobacterial cell wall, sharing some common features with all bacteria, represents an apparent ‘Achilles heel’ that has been targeted by TB chemotherapy since the advent of TB treatment. This complex structure composed of three distinct layers, peptidoglycan, arabinogalactan and mycolic acids, is vital in supporting cell growth, virulence and providing a barrier to antibiotics. The fundamental nature of cell wall synthesis and assembly has rendered the mycobacterial cell wall as the most widely exploited target of anti-TB drugs. This review provides an overview of the biosynthesis of the prominent cell wall components, highlighting the inhibitory mechanisms of existing clinical drugs and illustrating the potential of other unexploited enzymes as future drug targets.