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铁获取机制及其在鲍曼不动杆菌毒力中的作用。

Iron Acquisition Mechanisms and Their Role in the Virulence of Acinetobacter baumannii.

机构信息

Department of Microbiology, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.

出版信息

Infect Immun. 2022 Oct 20;90(10):e0022322. doi: 10.1128/iai.00223-22. Epub 2022 Sep 6.

Abstract

Iron is an essential element for survival of most organisms. One mechanism of host defense is to tightly chelate iron to several proteins to limit its extracellular availability. This has forced pathogens such as Acinetobacter baumannii to adapt mechanisms for the acquisition and utilization of iron even in iron-limiting conditions. A. baumannii uses a variety of iron acquisition strategies to meet its iron requirements. It can lyse erythrocytes to harvest the heme molecules, use iron-chelating siderophores, and use outer membrane vesicles to acquire iron. Iron acquisition pathways, in general, have been seen to affect many other virulence factors such as cell adherence, cell motility, and biofilm formation. The knowledge gained from research on iron acquisition led to the synthesis of the antibiotic cefiderocol, which uses iron uptake pathways for entry into the cell with some success as a novel cephalosporin. Understanding the mechanisms of iron acquisition of A. baumannii allows for insight into clinical infections and offer potential targets for novel antibiotics or potentiators of current drugs.

摘要

铁是大多数生物体生存所必需的元素。宿主防御的一种机制是将铁与几种蛋白质紧密螯合,以限制其细胞外的可用性。这迫使像鲍曼不动杆菌这样的病原体适应在缺铁条件下获取和利用铁的机制。鲍曼不动杆菌使用多种铁获取策略来满足其铁需求。它可以裂解红细胞以获取血红素分子,使用铁螯合的铁载体,并使用外膜囊泡来获取铁。一般来说,铁获取途径被认为会影响许多其他毒力因子,如细胞黏附、细胞运动和生物膜形成。从铁获取研究中获得的知识导致了抗生素头孢地尔的合成,该抗生素利用铁摄取途径进入细胞,作为一种新型头孢菌素取得了一定的成功。了解鲍曼不动杆菌的铁获取机制可以深入了解临床感染,并为新型抗生素或现有药物的增效剂提供潜在的靶点。

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