Iron Acquisition Strategies of Bacterial Pathogens

Abstract

Iron is an essential micronutrient for both microbes and humans alike. For well over half a century we have known that this element, in particular, plays a pivotal role in health and disease and, most especially, in shaping host-pathogen interactions. Intracellular iron concentrations serve as a critical signal in regulating the expression not only of high-affinity iron acquisition systems in bacteria, but also of toxins and other noted virulence factors produced by some major human pathogens. While we now are aware of many strategies that the host has devised to sequester iron from invading microbes, there are as many if not more sophisticated mechanisms by which successful pathogens overcome nutritional immunity imposed by the host. This review discusses some of the essential components of iron sequestration and scavenging mechanisms of the host, as well as representative Gram-negative and Gram-positive pathogens, and highlights recent advances in the field. Last, we address how the iron acquisition strategies of pathogenic bacteria may be exploited for the development of novel prophylactics or antimicrobials.

The Small Protein HemP Is a Transcriptional Activator for the Hemin Uptake Operon in Burkholderia multivorans ATCC 17616

“…The transcription of heme uptake gene clusters is also positively regulated by various mechanisms in the presence of heme. Such mechanisms are exemplified by (i) the system consisting of an inner membrane-spanning heme-sensor protein with anti-sigma-factor activity and an extracytoplasmic sigma factor (ECF) protein in P. aeruginosa and Serratia marcescens (19), (ii) the two-component hemeresponsive sensor-regulator system in Neisseria meningitidis (17), (iii) the LysR-type activator system in Vibrio spp. (18), and (iv) the HmuP activator (belonging to the HemP superfamily) system (Fig.…”

“…Although heme is very important for various metabolic functions in bacteria (20), free intracellular heme is also very toxic, most likely due to the generation of hydroxyl radical by the heme-mediated Fenton reaction (21). Several regulatory mechanisms for the expression of genes for heme uptake have been clarified (16)(17)(18)(19).…”

“…Fur is a global transcriptional regulator and regulates, either directly or indirectly, the transcription of a number of genes that are related to the acquisition and utilization of iron sources; Fur has also been indicated to regulate many genes that are not related to these functions (6,12). A number of bacterial species possess, in addition to the siderophore-mediated iron uptake systems, other systems for the uptake of external heme as a sole iron source, and TonB-dependent ABC-type heme transport systems are usually involved in the uptake of heme into the cytoplasm, where ferrous ion is released from heme (13)(14)(15)(16)(17)(18)(19). Although heme is very important for various metabolic functions in bacteria (20), free intracellular heme is also very toxic, most likely due to the generation of hydroxyl radical by the heme-mediated Fenton reaction (21).…”

Interaction between host genes and M. tuberculosis lineage can affect tuberculosis severity: evidence for coevolution

“…Iron is important for bacterial proliferation and competition for iron between host and pathogen has been well documented. Bacteria have previously been thought to evolve strategies for iron acquisition, further supporting the argument that SLC11A1 could be a plausible candidate for coevolution between humans and MTB, although it has not been determined which MTB genes are involved[45-47]. SLC11A1 polymorphisms have also been shown to associate with expression of IFN-γ, and the frequency of polymorphisms in SLC11A1 are different between populations, including between Europeans and Africans[29, 42, 43].…”

Медикаментозне Обмеження Доступності Іонів Заліза Для Патогенних Бактерій (Частина 1)

“…Бактерии используют ионы железа как хими-ческий элемент, который в соединениях может проявлять несколько (1-6) степеней окисления, а в биологических системах чаще всего встречает-ся в двух-или трехвалентной форме [42]. Однако соединения с двухвалентным железом (Fe 2+ ) из-за участия в реакции Фентона способствуют продук-ции высокого уровня активных кислородсодержа-щих метаболитов, а соединения с трехвалентным железом (Fe 3+ ) не растворимы в воде и характери-зуются низкой степенью биодоступности.…”