Staphylococcus aureus heme and siderophore-iron acquisition pathways

Conroy, Brigid; Grigg, J.C.; Kolesnikov, Maxim; Morales, L. Daniela; Murphy, M.E.P.

doi:10.1007/s10534-019-00188-2

Cited by 48 publications

(43 citation statements)

References 119 publications

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“…Its power in biology stems from its ability to toggle between Fe II (ferrous) and Fe III (ferric) oxidation states, with this redox activity playing key roles in metabolic enzymes (oxidases, catalases, peroxidases), electron transfer (ironsulfur proteins, cytochromes), and DNA synthesis (ribonucleotide reductases). During infections, many pathogens forage iron from human hemoglobin (Hb), as it contains ∼75-80% of the human body's total iron content in the form of heme (iron-protoporphyrin IX) (Parrow et al, 2013;Contreras et al, 2014;Wandersman and Delepelaire, 2014;Ma et al, 2015;Sheldon and Heinrichs, 2015;Choby and Skaar, 2016;Sheldon et al, 2016;Huang and Wilks, 2017;Conroy et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…The function of NEAT domains in microbial heme scavenging is best understood for Staphylococcus aureus, which employs the Iron-regulated surface determinant (Isd) system to capture heme-iron from Hb ( Figure 1A; Mazmanian et al, 2003;Nobles and Maresso, 2011;Sheldon and Heinrichs, 2015;Conroy et al, 2019). In the Isd system, four proteins containing NEAT domains are covalently attached to the cell wall (IsdA, IsdB, IsdC, and IsdH).…”

Section: Introductionmentioning

confidence: 99%

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NEAr Transporter (NEAT) Domains: Unique Surface Displayed Heme Chaperones That Enable Gram-Positive Bacteria to Capture Heme-Iron From Hemoglobin

2021

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Iron is an important micronutrient that is required by bacteria to proliferate and to cause disease. Many bacterial pathogens forage iron from human hemoglobin (Hb) during infections, which contains this metal within heme (iron–protoporphyrin IX). Several clinically important pathogenic species within the Firmicutes phylum scavenge heme using surface-displayed or secreted NEAr Transporter (NEAT) domains. In this review, we discuss how these versatile proteins function in the Staphylococcus aureus Iron-regulated surface determinant system that scavenges heme-iron from Hb. S. aureus NEAT domains function as either Hb receptors or as heme-binding chaperones. In vitro studies have shown that heme-binding NEAT domains can rapidly exchange heme amongst one another via transiently forming transfer complexes, leading to the interesting hypothesis that they may form a protein-wire within the peptidoglycan layer through which heme flows from the microbial surface to the membrane. In Hb receptors, recent studies have revealed how dedicated heme- and Hb-binding NEAT domains function synergistically to extract Hb’s heme molecules, and how receptor binding to the Hb-haptoglobin complex may block its clearance by macrophages, prolonging microbial access to Hb’s iron. The functions of NEAT domains in other Gram-positive bacteria are also reviewed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NEAr Transporter (NEAT) Domains: Unique Surface Displayed Heme Chaperones That Enable Gram-Positive Bacteria to Capture Heme-Iron From Hemoglobin

2021

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“…Moreover, S aureus can use heme as its sole source of Fe, which is taken up by the bacteria through the high-affinity heme transport apparatus called the Isd (iron responsive surface determinant) system. [49][50][51] How S aureus acquires Fe within macrophages and the source of the Fe that permits growth is presently unclear, and experiments are ongoing in our laboratory to understand how these bacteria accomplish this feat.…”

Section: Discussionmentioning

confidence: 99%

Rapid removal of phagosomal ferroportin in macrophages contributes to nutritional immunity

et al. 2021

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Nutrient sequestration is an essential facet of host innate immunity. Macrophages play a critical role in controlling iron availability through expression of the iron transport protein ferroportin (FPN), which extrudes iron from the cytoplasm to the extracellular milieu. During phagocytosis, the limiting phagosomal membrane, which derives from the plasmalemma, can be decorated with FPN and, if functional, will move iron from the cytosol into the phagosome lumen. This serves to feed iron to phagocytosed microbes and would be counterproductive to the many other known host mechanisms working to starve microbes of this essential metal. To understand how FPN is regulated during phagocytosis, we expressed FPN as a green fluorescent protein–fusion protein in macrophages and monitored its localization during uptake of various phagocytic targets, including Staphylococcus aureus, Salmonella enterica serovar Typhimurium, human erythrocytes, and immunoglobulin G opsonized latex beads. We find that FPN is rapidly removed, independently of Vps34 and PI(3)P, from early phagosomes and does not follow recycling pathways that regulate transferrin receptor recycling. Live-cell video microscopy showed that FPN movement on the phagosome is dynamic, with punctate and tubular structures forming before FPN is trafficked back to the plasmalemma. N-ethylmaleimide–sensitive factor, which disrupts soluble NSF attachment protein receptor (SNARE)–mediated membrane fusion and trafficking, prevented FPN removal from the phagosome. Our data support the hypothesis that removal of FPN from the limiting phagosomal membrane will, at the cellular level, ensure that iron cannot be pumped into phagosomes. We propose this as yet another mechanism of host nutritional immunity to subvert microbial growth.

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“…The Isd-internalized ferric ions are bound to staphyloferrin, a siderophore produced by the sbn gene cluster. SbnI is a DNA-binding regulatory protein that senses iron to regulate the synthesis of staphyloferrin [ 28 , 29 ]. The ferric-bound stapyloferrin is reduced to ferrous through interactions with iron uptake oxidoreductase (IruO), a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of Gram-Positive Bacterial Iron(III) Reduction for Kaolinite Clay Refinement

et al. 2021

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Recently, microbial-based iron reduction has been considered as a viable alternative to typical chemical-based treatments. The iron reduction is an important process in kaolin refining, where iron-bearing impurities in kaolin clay affects the whiteness, refractory properties, and its commercial value. In recent years, Gram-negative bacteria has been in the center stage of iron reduction research, whereas little is known about the potential use of Gram-positive bacteria to refine kaolin clay. In this study, we investigated the ferric reducing capabilities of five microbes by manipulating the microbial growth conditions. Out of the five, we discovered that Bacillus cereus and Staphylococcus aureus outperformed the other microbes under nitrogen-rich media. Through the biochemical changes and the microbial behavior, we mapped the hypothetical pathway leading to the iron reduction cellular properties, and found that the iron reduction properties of these Gram-positive bacteria rely heavily on the media composition. The media composition results in increased basification of the media that is a prerequisite for the cellular reduction of ferric ions. Further, these changes impact the formation of biofilm, suggesting that the cellular interaction for the iron(III)oxide reduction is not solely reliant on the formation of biofilms. This article reveals the potential development of Gram-positive microbes in facilitating the microbial-based removal of metal contaminants from clays or ores. Further studies to elucidate the corresponding pathways would be crucial for the further development of the field.

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Staphylococcus aureus heme and siderophore-iron acquisition pathways

Cited by 48 publications

References 119 publications

NEAr Transporter (NEAT) Domains: Unique Surface Displayed Heme Chaperones That Enable Gram-Positive Bacteria to Capture Heme-Iron From Hemoglobin

NEAr Transporter (NEAT) Domains: Unique Surface Displayed Heme Chaperones That Enable Gram-Positive Bacteria to Capture Heme-Iron From Hemoglobin

Rapid removal of phagosomal ferroportin in macrophages contributes to nutritional immunity

Elucidation of Gram-Positive Bacterial Iron(III) Reduction for Kaolinite Clay Refinement

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