Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, United States.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, United States.
Adv Microb Physiol. 2021;79:89-132. doi: 10.1016/bs.ampbs.2021.07.004. Epub 2021 Aug 13.
Iron is an essential micronutrient for all bacteria but presents a significant challenge given its limited bioavailability. Furthermore, iron's toxicity combined with the need to maintain iron levels within a narrow physiological range requires integrated systems to sense, regulate and transport a variety of iron complexes. Most bacteria encode systems to chelate and transport ferric iron (Fe) via siderophore receptor mediated uptake or via cytoplasmic energy dependent transport systems. Pathogenic bacteria have further lowered the barrier to iron acquisition by employing systems to utilize haem as a source of iron. Haem, a lipophilic and toxic molecule, presents a significant challenge for transport into the cell. As such pathogenic bacteria have evolved sophisticated cell surface signaling (CSS) and transport systems to sense and obtain haem from the host. Once internalized haem is cleaved by both oxidative and non-oxidative mechanisms to release iron. Herein we summarize our current understanding of the mechanism of haem sensing, uptake and utilization in Pseudomonas aeruginosa, its role in pathogenesis and virulence, and the potential of these systems as antimicrobial targets.
铁是所有细菌必需的微量元素，但由于其生物利用度有限，这是一个重大挑战。此外，铁的毒性加上需要将铁水平维持在狭窄的生理范围内，这需要集成系统来感应、调节和运输各种铁复合物。大多数细菌通过 siderophore 受体介导的摄取或通过细胞质能量依赖的转运系统来编码螯合和转运三价铁 (Fe) 的系统。致病性细菌通过利用血红素作为铁源的系统进一步降低了获取铁的障碍。血红素是一种亲脂性和有毒的分子，对进入细胞的运输构成了重大挑战。因此，致病性细菌已经进化出复杂的细胞表面信号（CSS）和转运系统，以从宿主中感应和获取血红素。一旦内化，血红素通过氧化和非氧化机制被切割以释放铁。本文总结了我们目前对铜绿假单胞菌血红素感应、摄取和利用的机制、其在发病机制和毒力中的作用以及这些系统作为抗菌靶点的潜力的理解。
