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Iron Acquisition in Mycobacterium tuberculosis.
Chemical Reviews ( IF 51.4 ) Pub Date : 2018-11-26 , DOI: 10.1021/acs.chemrev.8b00285 Alex Chao , Paul J Sieminski , Cedric P Owens 1 , Celia W Goulding
Chemical Reviews ( IF 51.4 ) Pub Date : 2018-11-26 , DOI: 10.1021/acs.chemrev.8b00285 Alex Chao , Paul J Sieminski , Cedric P Owens 1 , Celia W Goulding
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The highly contagious disease tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (Mtb), which has been evolving drug resistance at an alarming rate. Like all human pathogens, Mtb requires iron for growth and virulence. Consequently, Mtb iron transport is an emerging drug target. However, the development of anti-TB drugs aimed at these metabolic pathways has been restricted by the dearth of information on Mtb iron acquisition. In this Review, we describe the multiple strategies utilized by Mtb to acquire ferric iron and heme iron. Mtb iron uptake is a complex process, requiring biosynthesis and subsequent export of Mtb siderophores, followed by ferric iron scavenging and ferric-siderophore import into Mtb. Additionally, Mtb possesses two possible heme uptake pathways and an Mtb-specific mechanism of heme degradation that yields iron and novel heme-degradation products. We conclude with perspectives for potential therapeutics that could directly target Mtb heme and iron uptake machineries. We also highlight how hijacking Mtb heme and iron acquisition pathways for drug import may facilitate drug transport through the notoriously impregnable Mtb cell wall.
中文翻译：
结核分枝杆菌中的铁获取。
传染性很强的结核病（TB）是由结核分枝杆菌（Mtb）引起的，该病菌的耐药性正在以惊人的速度发展。像所有人类病原体一样，Mtb需要铁才能生长和致病。因此，Mtb铁运输是新兴的药物目标。但是，针对这些代谢途径的抗结核药物的开发受到缺乏Mtb铁获取信息的限制。在这篇综述中，我们描述了Mtb用来获取三价铁和血红素铁的多种策略。吸收Mtb铁是一个复杂的过程，需要生物合成和随后的Mtb铁载体的出口，然后是三价铁清除和铁-铁载体导入Mtb。此外，Mtb具有两种可能的血红素摄取途径，以及一种Mtb特异性的血红素降解机制，可产生铁和新型的血红素降解产物。我们以可以直接针对Mtb血红素和铁吸收机制的潜在疗法的观点得出结论。我们还强调了劫持Mtb血红素和铁的获取途径以用于药物进口可能如何促进药物通过臭名昭著的Mtb细胞壁的运输。
更新日期：2018-11-26
中文翻译：
结核分枝杆菌中的铁获取。
传染性很强的结核病（TB）是由结核分枝杆菌（Mtb）引起的，该病菌的耐药性正在以惊人的速度发展。像所有人类病原体一样，Mtb需要铁才能生长和致病。因此，Mtb铁运输是新兴的药物目标。但是，针对这些代谢途径的抗结核药物的开发受到缺乏Mtb铁获取信息的限制。在这篇综述中，我们描述了Mtb用来获取三价铁和血红素铁的多种策略。吸收Mtb铁是一个复杂的过程，需要生物合成和随后的Mtb铁载体的出口，然后是三价铁清除和铁-铁载体导入Mtb。此外，Mtb具有两种可能的血红素摄取途径，以及一种Mtb特异性的血红素降解机制，可产生铁和新型的血红素降解产物。我们以可以直接针对Mtb血红素和铁吸收机制的潜在疗法的观点得出结论。我们还强调了劫持Mtb血红素和铁的获取途径以用于药物进口可能如何促进药物通过臭名昭著的Mtb细胞壁的运输。
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