Iron Acquisition Systems of Gram-negative Bacterial Pathogens Define TonB-Dependent Pathways to Novel Antibiotics
journal contributionposted on 16.03.2021, 20:32 by Phillip E. Klebba, Salete M. C. Newton, David A. Six, Ashish Kumar, Taihao Yang, Brittany L. Nairn, Colton Munger, Somnath Chakravorty
Iron is an indispensable metabolic cofactor in both pro- and eukaryotes, which engenders a natural competition for the metal between bacterial pathogens and their human or animal hosts. Bacteria secrete siderophores that extract Fe3+ from tissues, fluids, cells, and proteins; the ligand gated porins of the Gram-negative bacterial outer membrane actively acquire the resulting ferric siderophores, as well as other iron-containing molecules like heme. Conversely, eukaryotic hosts combat bacterial iron scavenging by sequestering Fe3+ in binding proteins and ferritin. The variety of iron uptake systems in Gram-negative bacterial pathogens illustrates a range of chemical and biochemical mechanisms that facilitate microbial pathogenesis. This document attempts to summarize and understand these processes, to guide discovery of immunological or chemical interventions that may thwart infectious disease.
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iron-containing moleculesiron Acquisition Systemseukaryotic hosts combatNovel Antibiotics Ironchemical interventionsTonB-Dependent Pathwaysguide discoveryBacteria secrete siderophoresiron uptake systemspathogenFeferric siderophoresGram-negativeligand gated porinsbinding proteinsdocument attemptsanimal hosts