Streptococcus pneumoniae, a human pathogen bacterium, can support its growth using haemoglobin (Hb) and haem as sole iron sources, but not when holo-transferrin or holo-lactoferrin is supplied. For this reason, it is easy to think that the principal iron sources for this pathogen inside humans are Hb and haem. Unfortunately, the mechanism has been poorly studied. The findings presented in this study are the first efforts that attempted to explain the mechanism involved in iron acquisition of this pathogen. This pathogen was capable of supporting its viability when iron sources such as Hb or haem were supplied. Membranes of S. pneumoniae were separated and their respective proteins were solubilized in order to be purified by haem-affinity chromatography. This strategy allowed us to purify seven membrane proteins. An experiment of competence with haem and iron showed two potential haem and Hb-binding proteins. Their Hb-binding function was confirmed by overlay assay using Hb and their respective identities were obtained by mass spectrometry. Then by amino acid alignment analysis, the motif involved in binding of Hb or haem was revealed. These results are the first findings that attempt to explain the mechanisms developed by S. pneumoniae to acquire iron from Hb or haem in the host, which could allow a better understanding of the biology of this bacterium.
The capability of Entamoeba histolytica to use hemoglobin (Hb) as an iron source has been documented. However, the underlying mechanism to acquire iron from this source is poorly understood. In the present work, an in silico analysis in the E. histolytica genome (Pathema database) allowed us to identify a gene coding for a putative 26-kDa protein (Ehhmbp26) which contains the motifs necessary for Hb-binding. The purified Ehhmbp26 protein was able to bind Hb. Albeit with less efficiency, trophozo...
Last. Olaf Schneewind(U of C: University of Chicago)H-Index: 113
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Acquisition of iron is necessary for the replication of nearly all bacterial pathogens; however, iron of vertebrate hosts is mostly sequestered by heme and bound to hemoglobin within red blood cells. In Bacillus anthracis, the spore-forming agent of anthrax, the mechanisms of iron scavenging from hemoglobin are unknown. We report here that B. anthracis secretes IsdX1 and IsdX2, two NEAT domain proteins, to remove heme from hemoglobin, thereby retrieving iron for bacterial growth. Unlike other Gr...
Serratia marcescens hemTUV genes encoding a potential heme permease were cloned in Escherichia coli recombinant mutant FB827 dppF::Km(pAM 238-hasR). This strain, which expresses HasR, a foreign heme outer membrane receptor, is potentially capable of using heme as an iron source. However, this process is invalidated due to a dppF::Km mutation which inactivates the Dpp heme/peptide permease responsible for heme, dipeptide, and δ-aminolevulinic (ALA) transport through the E. coli inner membrane. We...
Last. Eric P. Skaar(Vandy: Vanderbilt University)H-Index: 69
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The pathogenesis of human infections caused by the gram-positive microbe Staphylococcus aureus has been previously shown to be reliant on the acquisition of iron from host hemoproteins. The iron-regulated surface determinant system (Isd) encodes a heme transport apparatus containing three cell wall-anchored proteins (IsdA, IsdB, and IsdH) that are exposed on the staphylococcal surface and hence have the potential to interact with human hemoproteins. Here we report that S. aureus can utilize the ...
We have previously identified and characterized a heme/hemoglobin receptor, HmuR, in Porphyromonas gingivalis. To analyze the conserved amino acid residues of HmuR that may be involved in hemin/hemoprotein binding and utilization, we constructed a series of P. gingivalis A7436 hmuR mutants with amino acid replacements and characterized the ability of these mutants to utilize hemin and hemoproteins. Site-directed mutagenesis was employed to introduce mutations H95A, H434A, H95A-H434A, YRAP420-423...
▪ Abstract Iron is an essential element for most organisms, including bacteria. The oxidized form is insoluble, and the reduced form is highly toxic for most macromolecules and, in biological systems, is generally sequestrated by iron- and heme-carrier proteins. Thus, despite its abundance on earth, there is practically no free iron available for bacteria whatever biotope they colonize. To fulfill their iron needs, bacteria have multiple iron acquisition systems, reflecting the diversity of thei...
Iron is essential to virtually all organisms, but poses problems of toxicity and poor solubility. Bacteria have evolved various mechanisms to counter the problems imposed by their iron dependence, allowing them to achieve effective iron homeostasis under a range of iron regimes. Highly efficient iron acquisition systems are used to scavenge iron from the environment under iron-restricted conditions. In many cases, this involves the secretion and internalisation of extracellular ferric chelators ...
The hemolytic Streptococcus pyogenes can use a variety of heme compounds as an iron source. In this study, we investigate hemoprotein utilization by S. pyogenes. We demonstrate that surface proteins contribute to the binding of hemoproteins to S. pyogenes. We identify an ABC transporter from the iron complex family named sia for streptococcal iron acquisition, which consists of a lipoprotein (siaA), membrane permease (siaB), and ATPase (siaC). The sia transporter is part of a highly conserved, i...
Cells growing in aerobic environments have developed intricate strategies to overcome the scarcity of iron, an essential nutrient. In Gram-negative bacteria, high-affinity iron acquisition requires outer membrane-localized proteins that bind iron chelates at the cell surface and promote their uptake. Transport of bound chelates across the outer membrane depends upon TonB–ExbB–ExbD, a cytoplasmic membrane-localized complex that transduces energy from the proton motive force to high-affinity recep...
Bacterial extracellular haemophores also named HasA for haem acquisition system form an independent family of haemoproteins that take up haem from host haeme carriers and shuttle it to specific receptors (HasR). Haemophore receptors are required for the haemophore-dependent haem acquisition pathway and alone allow free or haemoglobin-bound haem uptake, but the synergy between the haemophore and its receptor greatly facilitates this uptake. The three-dimensional structure of the Serratia marcesce...
Yunnan Province, China is thought to be the original source of biovar Orientalis of Yersinia pestis, the causative agent of the third plague pandemic that has spread globally since the end of the 19th century. Although encompassing a large area of natural plague foci, Y. pestis strains have rarely been found in live rodents during surveillance in Yunnan, and most isolates are from rodent corpses and their fleas. In 2017, 10 Y. pestis strains were isolated from seven live rodents and three fleas ...
Streptococcus pneumoniae grows in biofilms during both asymptomatic colonization and infection. Pneumococcal biofilms on abiotic surfaces exhibit delayed growth, lower biomass, and lack the structures seen on epithelial cells or during nasopharyngeal carriage. We show here that adding hemoglobin to the medium activated unusually early and vigorous biofilm growth in multiple S. pneumoniae serotypes grown in batch cultures on abiotic surfaces. Human blood (but not serum, heme, or iron) also stimul...
Nasopharyngeal colonization by Streptococcus pneumoniae is a prerequisite for pneumococcal transmission and disease. Current vaccines protect only against disease and colonization caused by a limited number of serotypes, consequently allowing serotype replacement and transmission. Therefore, the development of a broadly protective vaccine against colonization, transmission and disease is desired but requires a better understanding of pneumococcal adaptation to its natural niche. Hence, we measur...
Last. Sarah H. Atkinson(Kenya Medical Research Institute)H-Index: 16
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Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated wi...
Streptococcus pneumoniae (Spn) must acquire iron from the host to establish infection. We examined the impact of hemoglobin, the largest iron reservoir in the body, on pneumococcal physiology. Supplementation with hemoglobin allowed Spn to resume growth in an iron-deplete medium. Pneumococcal growth with hemoglobin was unusually robust, exhibiting a prolonged logarithmic growth, higher biomass, and extended viability in both iron-deplete and standard medium. We observed the hemoglobin-dependent ...
Last. Jae Jun Song(KU: Korea University)H-Index: 20
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Introduction: Air pollutants such as Asian sand dust (ASD) and Streptococcus pneumoniae are risk factors for otitis media (OM). In this study, we evaluate the role of ASD in pneumococcal in vitro biofilm growth and colonization on human middle ear epithelium cells (HMEECs) and rat middle ear using the rat OM model. Methods: S. pneumoniae D39 in vitro biofilm growth in the presence of ASD (50-300 mug/ml) was evaluated in metal ion-free BHI medium using CV-microplate assay, colony-forming unit (cf...
Last. Qing-Yu He(JNU: Jinan University)H-Index: 57
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In most bacteria, iron plays a vital role in pathogenesis processes. To support survival and infection, Streptococcus pneumoniae has evolved three ABC transporters, PiaABC, PiuABC, and PitABC. Moreover, indirect evidence supports that operon 804 may be a novel ABC transporter in S. pneumoniae. We have recently described the identification of lipoprotein SPD_1609 in operon 804; however, whether the SPD_1609 protein affects the virulence of S. pneumoniae has not yet been studied. In the present wo...
Antimicrobial photodynamic therapy (aPDT) is a promising method for the topical treatment of drug-resistant staphylococcal infections and can be further improved by identifying mechanisms that increase the specificity of photosensitizer uptake by bacteria. Here we show that Ga(III)-protoporphyrin IX chloride (Ga-PpIX), a fluorescent hemin analog with previously undisclosed photosensitizing properties, can be taken up within seconds by Staphylococcus aureus including multidrug-resistant strains s...
Last. Xuesong Sun(JNU: Jinan University)H-Index: 18
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Streptococcus pneumoniae, a gram-positive human pathogen, has evolved three main transporters for iron acquisition from the host: PiaABC, PiuABC, and PitABC. Our previous study had shown that the mRNA and protein levels of SPD_1590 are significantly upregulated in the piuA/piaA/pitA triple mutant, suggesting that SPD_1590 might be a novel iron transporter in S. pneumoniae. In the present study, using spd1590-knockout, -complemented, and -overexpressing strains and the purified SPD_1590 protei...
Last. Günter Weiss(Innsbruck Medical University)H-Index: 79
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Abstract The acute-phase response is triggered by the presence of infectious agents and danger signals which indicate hazards for the integrity of the mammalian body. One central feature of this response is the sequestration of iron into storage compartments including macrophages. This limits the availability of this essential nutrient for circulating pathogens, a host defence strategy known as ‘nutritional immunity’. Iron metabolism and the immune response are intimately linked. In infections, ...
