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1
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Orzel B, Pelucelli A, Ostrowska M, Potocki S, Kozlowski H, Peana M, Gumienna-Kontecka E. Fe(II), Mn(II), and Zn(II) Binding to the C-Terminal Region of FeoB Protein: An Insight into the Coordination Chemistry and Specificity of the Escherichia coli Fe(II) Transporter. Inorg Chem 2023; 62:18607-18624. [PMID: 37910812 PMCID: PMC10647171 DOI: 10.1021/acs.inorgchem.3c02910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 10/03/2023] [Accepted: 10/03/2023] [Indexed: 11/03/2023]
Abstract
The interactions between two peptide ligands [Ac763CCAASTTGDCH773 (P1) and Ac743RRARSRVDIELLATRKSVSSCCAASTTGDCH773 (P2)] derived from the cytoplasmic C-terminal region of Eschericha coli FeoB protein and Fe(II), Mn(II), and Zn(II) ions were investigated. The Feo system is regarded as the most important bacterial Fe(II) acquisition system, being one of the key virulence factors, especially in anaerobic conditions. Located in the inner membrane of Gram-negative bacteria, FeoB protein transports Fe(II) from the periplasm to the cytoplasm. Despite its crucial role in bacterial pathogenicity, the mechanism in which the metal ion is trafficked through the membrane is not yet elucidated. In the gammaproteobacteria class, the cytoplasmic C-terminal part of FeoB contains conserved cysteine, histidine, and glutamic and aspartic acid residues, which could play a vital role in Fe(II) binding in the cytoplasm, receiving the metal ion from the transmembrane helices. In this work, we characterized the complexes formed between the whole cytosolic C-terminal sequence of E. coli FeoB (P2) and its key polycysteine region (P1) with Fe(II), Mn(II), and Zn(II) ions, exploring the specificity of the C-terminal region of FeoB. With the help of a variety of potentiometric, spectroscopic (electron paramagnetic resonance and NMR), and spectrometric (electrospray ionization mass spectrometry) techniques and molecular dynamics, we propose the metal-binding modes of the ligands, compare their affinities toward the metal ions, and discuss the possible physiological role of the C-terminal region of E. coli FeoB.
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Affiliation(s)
- Bartosz Orzel
- Faculty
of Chemistry, University of Wrocław, 50-383 Wrocław, Poland
| | - Alessio Pelucelli
- Department
of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, 07100 Sassari, Italy
| | | | - Slawomir Potocki
- Faculty
of Chemistry, University of Wrocław, 50-383 Wrocław, Poland
| | - Henryk Kozlowski
- Faculty
of Chemistry, University of Wrocław, 50-383 Wrocław, Poland
- Department
of Health Sciences, University of Opole, Katowicka 68, 45-060 Opole, Poland
| | - Massimiliano Peana
- Department
of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, 07100 Sassari, Italy
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2
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Huang Z, Zhu Y, Li X, Yao Z, Ge R. The mechanisms of metronidazole resistance of Helicobacter pylori: A transcriptomic and biochemical study. Microb Pathog 2023; 183:106303. [PMID: 37595811 DOI: 10.1016/j.micpath.2023.106303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 07/24/2023] [Accepted: 08/09/2023] [Indexed: 08/20/2023]
Abstract
Helicobacter pylori (H. pylori) is a bacterial pathogen in the stomach, causing gastritis, gastric ulcer, duodenal ulcer and even gastric cancer. The triple therapy containing one bismuth-containing compound or a proton-pump inhibitor with two antibiotics was the cornerstone of the treatment of H. pylori infections. However the drug resistance of Helicobacter pylori is more and more common, which leads to the continued decline in the radical cure rate. The purpose of this study was to investigate the mechanism of metronidazole resistance of H. pylori through transcriptomics and biochemical characterizations. In this study, a 128-time-higher metronidazole-resistant H. pylori strain compared to the sensitive strain was domesticated, and 374 significantly differential genes were identified by transcriptomic sequencing as compared to the metronidazole-sensitive strain. Through GO and KEGG enrichment analysis, antibiotic-resistance pathways were found to be mainly involved in redox, biofilm formation and ABC transportation, and the results were verified by qRT-PCR. The subsequent biochemical analysis found that the urease activity of the drug-resistant strain decreased, and whereas the capabilities of bacterial energy production, membrane production and diffusion ability increased. The work here will drop hints for the mechanisms of antibiotic-resistance of H. pylori and provide promising biomarkers for the further development of new-kind drugs to treat metronidazole-resistant H. pylori.
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Affiliation(s)
- Zeyuan Huang
- The Laboratory of Metalloproteins, College of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Yulin Zhu
- The Laboratory of Metalloproteins, College of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Xinhang Li
- The Laboratory of Metalloproteins, College of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Zihui Yao
- The Laboratory of Metalloproteins, College of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Ruiguang Ge
- The Laboratory of Metalloproteins, College of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.
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3
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Cui F, Fan R, Wang D, Li J, Li T. Research progress on iron uptake pathways and mechanisms of foodborne microorganisms and their application in the food sector. Crit Rev Food Sci Nutr 2023; 64:8892-8910. [PMID: 37099732 DOI: 10.1080/10408398.2023.2204491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
Iron is one of the essential nutrients for almost all microorganisms. Under iron-limited conditions, bacteria can secrete siderophores to the outside world to absorb iron for survival. This process requires the coordinated action of energy-transducing proteins, transporters, and receptors. The spoilage factors of some spoilage bacteria and the pathogenic mechanism of pathogenic bacteria are also closely related to siderophores. Meanwhile, some siderophores have also gradually evolved toward beneficial aspects. First, a variety of siderophores are classified into three aspects. In addition, representative iron uptake systems of Gram-negative and Gram-positive bacteria are described in detail to understand the common and specific pathways of iron uptake by various bacteria. In particular, the causes of siderophore-induced bacterial pathogenicity and the methods and mechanisms of inhibiting bacterial iron absorption under the involvement of siderophores are presented. Then, the application of siderophores in the food sector is mainly discussed, such as improving the food quality of dairy products and meat, inhibiting the attack of pathogenic bacteria on food, improving the plant growth environment, and promoting plant growth. Finally, this review highlights the unresolved fate of siderophores in the iron uptake system and emphasizes further development of siderophore-based substitutes for traditional drugs, new antibiotic-resistance drugs, and vaccines in the food and health sectors.
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Affiliation(s)
- Fangchao Cui
- College of Food Science and Technology, Bohai University, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Jinzhou, China
| | - Rongsen Fan
- College of Food Science and Technology, Bohai University, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Jinzhou, China
| | - Dangfeng Wang
- College of Food Science and Technology, Bohai University, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Jinzhou, China
- College of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Jianrong Li
- College of Food Science and Technology, Bohai University, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Jinzhou, China
| | - Tingting Li
- Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), Ministry of Education, Dalian, China
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4
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Liu J, Li X, Zhu Y, Ge R. Molecular Mechanisms of Bismuth-containing Drugs Against Helicobacter pylori: a Further Update. CURRENT PHARMACOLOGY REPORTS 2022; 9:59-65. [DOI: 10.1007/s40495-022-00305-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/31/2022] [Indexed: 01/04/2025]
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5
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Pellizza L, Bialer MG, Sieira R, Aran M. MliR, a novel MerR-like regulator of iron homeostasis, impacts metabolism, membrane remodeling, and cell adhesion in the marine Bacteroidetes Bizionia argentinensis. Front Microbiol 2022; 13:987756. [PMID: 36118216 PMCID: PMC9478572 DOI: 10.3389/fmicb.2022.987756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
The MerR family is a group of transcriptional activators with conserved N-terminal helix-turn-helix DNA binding domains and variable C-terminal effector binding regions. In most MerR proteins the effector binding domain (EBD) contains a cysteine center suited for metal binding and mediates the response to environmental stimuli, such as oxidative stress, heavy metals or antibiotics. We here present a novel transcriptional regulator classified in the MerR superfamily that lacks an EBD domain and has neither conserved metal binding sites nor cysteine residues. This regulator from the psychrotolerant bacteria Bizionia argentinensis JUB59 is involved in iron homeostasis and was named MliR (MerR-like iron responsive Regulator). In silico analysis revealed that homologs of the MliR protein are widely distributed among different bacterial species. Deletion of the mliR gene led to decreased cell growth, increased cell adhesion and filamentation. Genome-wide transcriptomic analysis showed that genes associated with iron homeostasis were downregulated in mliR-deletion mutant. Through nuclear magnetic resonance-based metabolomics, ICP-MS, fluorescence microscopy and biochemical analysis we evaluated metabolic and phenotypic changes associated with mliR deletion. This work provides the first evidence of a MerR-family regulator involved in iron homeostasis and contributes to expanding our current knowledge on relevant metabolic pathways and cell remodeling mechanisms underlying in the adaptive response to iron availability in bacteria.
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Fischer F, Vorontsov E, Turlin E, Malosse C, Garcia C, Tabb DL, Chamot-Rooke J, Percudani R, Vinella D, De Reuse H. Expansion of nickel binding- and histidine-rich proteins during gastric adaptation of Helicobacter species. METALLOMICS : INTEGRATED BIOMETAL SCIENCE 2022; 14:6674772. [PMID: 36002005 DOI: 10.1093/mtomcs/mfac060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 08/17/2022] [Indexed: 11/14/2022]
Abstract
Acquisition and homeostasis of essential metals during host colonization by bacterial pathogens rely on metal uptake, trafficking and storage proteins. How these factors have evolved within bacterial pathogens is poorly defined. Urease, a nickel enzyme, is essential for Helicobacter pylori to colonize the acidic stomach. Our previous data suggest that acquisition of nickel transporters and a Histidine-rich protein (HRP) involved in nickel storage in H. pylori and gastric Helicobacter spp. have been essential evolutionary events for gastric colonization. Using bioinformatics, proteomics and phylogenetics, we extended this analysis to determine how evolution has framed the repertoire of HRPs among 39 Epsilonproteobacteria; 18 gastric and 11 non-gastric enterohepatic (EH) Helicobacter spp., as well as 10 other Epsilonproteobacteria. We identified a total of 213 HRPs distributed in 22 protein families named orthologous groups (OG) with His-rich domains, including 15 newly described OGs. Gastric Helicobacter spp. are enriched in HRPs (7.7 ± 1.9 HRPs/strain) as compared to EH Helicobacter spp. (1.9 ± 1.0 HRPs/strain) with a particular prevalence of HRPs with C-terminal Histidine-rich domains in gastric species. The expression and nickel-binding capacity of several HRPs was validated in five gastric Helicobacter spp. We established the evolutionary history of new HRP families, such as the periplasmic HP0721-like proteins and the HugZ-type heme-oxygenases. The expansion of Histidine-rich extensions in gastric Helicobacter spp. proteins is intriguing but can tentatively be associated with the presence of the urease nickel-enzyme. We conclude that this HRP expansion is associated with unique properties of organisms that rely on large intracellular nickel amounts for their survival.
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Affiliation(s)
- Frédéric Fischer
- Institut Pasteur, Département de Microbiologie, Unité Pathogenèse de Helicobacter, UMR CNRS 6047, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE.,Génétique Moléculaire, Génomique, Microbiologie, UMR 7156, Université de Strasbourg, Institut de Physiologie et Chimie Biologiques, 4 allée Konrad Roentgen, 67084 Strasbourg, FRANCE
| | - Egor Vorontsov
- Institut Pasteur, Department of Structural Biology and Chemistry, Université Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE.,Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Box 413, 40530 Gothenburg, SWEDEN
| | - Evelyne Turlin
- Institut Pasteur, Département de Microbiologie, Unité Pathogenèse de Helicobacter, UMR CNRS 6047, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE
| | - Christian Malosse
- Institut Pasteur, Department of Structural Biology and Chemistry, Université Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE
| | - Camille Garcia
- Institut Pasteur, Department of Structural Biology and Chemistry, Université Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE
| | - David L Tabb
- Institut Pasteur, Department of Structural Biology and Chemistry, Université Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE
| | - Julia Chamot-Rooke
- Institut Pasteur, Department of Structural Biology and Chemistry, Université Paris Cité, CNRS UAR 2024, Mass Spectrometry for Biology Unit, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE
| | - Riccardo Percudani
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124, Parma, ITALY
| | - Daniel Vinella
- Institut Pasteur, Département de Microbiologie, Unité Pathogenèse de Helicobacter, UMR CNRS 6047, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE
| | - Hilde De Reuse
- Institut Pasteur, Département de Microbiologie, Unité Pathogenèse de Helicobacter, UMR CNRS 6047, 28 rue du Dr Roux 75724 PARIS Cedex 15 FRANCE
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7
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de Jesús Olivares-Trejo J, Elizbeth Alvarez-Sánchez M. Proteins of Streptococcus pneumoniae Involved in Iron Acquisition. Infect Dis (Lond) 2022. [DOI: 10.5772/intechopen.101668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Streptococcus pneumoniae is a human pathogen bacterium capable of using hemoglobin (Hb) and haem as a single iron source but not in presence of lactoferrin. This bacterium has developed a mechanism through the expression of several membrane proteins that bind to iron sources, between them a lipoprotein of 37 kDa called Spbhp-37 (Streptococcus pneumoniae haem-binding protein) involved in iron acquisition. The Spbhp-37 role is to maintain the viability of S. pneumoniae in presence of Hb or haem. This mechanism is relevant during the invasion of S. pneumoniae to human tissue for the acquisition of iron from hemoglobin or haem as an iron source.
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8
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Cheng X, Liu W, Wang Z, Yang R, Yu L, Du Q, Ge A, Liu C, Chi Z. Improved triple-module fluorescent biosensor for the rapid and ultrasensitive detection of Campylobacter jejuni in livestock and dairy. Food Control 2022. [DOI: 10.1016/j.foodcont.2022.108905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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9
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Öztekin M, Yılmaz B, Ağagündüz D, Capasso R. Overview of Helicobacter pylori Infection: Clinical Features, Treatment, and Nutritional Aspects. Diseases 2021; 9:66. [PMID: 34698140 PMCID: PMC8544542 DOI: 10.3390/diseases9040066] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 09/11/2021] [Accepted: 09/23/2021] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a 0.5-1 µm wide, 2-4 µm long, short helical, S-shaped Gram-negative microorganism. It is mostly found in the pyloric region of the stomach and causes chronic gastric infection. It is estimated that these bacteria infect more than half of the world's population. The mode of transmission and infection of H. pylori is still not known exactly, but the faecal-oral and oral-oral routes via water or food consumption are thought to be a very common cause. In the last three decades, research interest has increased regarding the pathogenicity, microbial activity, genetic predisposition, and clinical treatments to understand the severity of gastric atrophy and gastric cancer caused by H. pylori. Studies have suggested a relationship between H. pylori infection and malabsorption of essential micronutrients, and noted that H. pylori infection may affect the prevalence of malnutrition in some risk groups. On the other hand, dietary factors may play a considerably important role in H. pylori infection, and it has been reported that an adequate and balanced diet, especially high fruit and vegetable consumption and low processed salty food consumption, has a protective effect against the outcomes of H. pylori infection. The present review provides an overview of all aspects of H. pylori infection, such as clinical features, treatment, and nutrition.
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Affiliation(s)
- Merve Öztekin
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Emek, Ankara 06490, Turkey; (M.Ö.); (B.Y.)
| | - Birsen Yılmaz
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Emek, Ankara 06490, Turkey; (M.Ö.); (B.Y.)
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Çukurova University, Sarıçam, Adana 01330, Turkey
| | - Duygu Ağagündüz
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Emek, Ankara 06490, Turkey; (M.Ö.); (B.Y.)
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
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10
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Melo J, Pinto V, Fernandes T, Malheiro AR, Osório H, Figueiredo C, Leite M. Isolation Method and Characterization of Outer Membranes Vesicles of Helicobacter pylori Grown in a Chemically Defined Medium. Front Microbiol 2021; 12:654193. [PMID: 34149641 PMCID: PMC8206784 DOI: 10.3389/fmicb.2021.654193] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 04/27/2021] [Indexed: 02/05/2023] Open
Abstract
Outer membrane vesicles (OMVs) are small vesicles constitutively shed by all Gram-negative bacterium, which have been proposed to play a role in Helicobacter pylori persistence and pathogenesis. The methods currently available for the isolation of H. pylori OMVs are diverse and time-consuming, raising the need for a protocol standardization, which was the main aim of this study. Here, we showed that the chemically defined F12 medium, supplemented with cholesterol, nutritionally supports bacterial growth and maintains H. pylori viability for at least 72 h. Additionally, we developed an abridged protocol for isolation of OMVs from these bacterial cultures, which comprises a low-speed centrifugation, supernatant filtration through a 0.45 μm pore, and two ultracentrifugations for OMVs’ recovery and washing. Using this approach, a good yield of highly pure bona fide OMVs was recovered from cultures of different H. pylori strains and in different periods of bacterial growth, as assessed by nanoparticle tracking analysis, transmission electron microscopy (TEM), and proteomic analyses, confirming the reliability of the protocol. Analysis of the proteome of OMVs isolated from H. pylori F12-cholesterol cultures at different time points of bacterial growth revealed differentially expressed proteins, including the vacuolating cytotoxin VacA. In conclusion, this work proposes a time- and cost-efficient protocol for the isolation of H. pylori OMVs from a chemically defined culture medium that is suitable for implementation in research and in the biopharmaceutical field.
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Affiliation(s)
- Joana Melo
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal.,ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Vanessa Pinto
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
| | - Tânia Fernandes
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
| | - Ana R Malheiro
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
| | - Hugo Osório
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal.,Departamento de Patologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Ceu Figueiredo
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal.,Departamento de Patologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Marina Leite
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Ipatimup - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal.,Departamento de Patologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
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11
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Khasheii B, Mahmoodi P, Mohammadzadeh A. Siderophores: Importance in bacterial pathogenesis and applications in medicine and industry. Microbiol Res 2021; 250:126790. [PMID: 34098495 DOI: 10.1016/j.micres.2021.126790] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/14/2021] [Accepted: 05/24/2021] [Indexed: 12/21/2022]
Abstract
Iron is an essential element for all microorganisms. Siderophores are low-weight, high-affinity iron chelating molecules produced in response to iron deficiency by Gram-positive and Gram-negative bacteria which also known as essential virulence factors of bacteria. Several studies have indicated that defective production and/or function of these molecules as well as iron acquisition systems in pathogens are associated with a reduction in pathogenicity of bacteria. Because of their potential role in various biological pathways, siderophores have been received special attention as secondary metabolites. Siderophores can detect iron levels in a variety of environments with a biosensor function. In medicine, siderophores are used to deliver antibiotics (Trojan horse strategy) to resistant bacteria and to treat diseases such as cancer and malaria. In this review, we discuss the iron acquisition pathways in Gram-positive and -negative bacteria, importance of siderophore production in pathogenesis of bacteria, classification of siderophores, and main applications of siderophores in medicine and industry.
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Affiliation(s)
- Behnoush Khasheii
- Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran
| | - Pezhman Mahmoodi
- Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran.
| | - Abdolmajid Mohammadzadeh
- Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran
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12
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Jaworska K, Ludwiczak M, Murawska E, Raczkowska A, Brzostek K. The Regulator OmpR in Yersinia enterocolitica Participates in Iron Homeostasis by Modulating Fur Level and Affecting the Expression of Genes Involved in Iron Uptake. Int J Mol Sci 2021; 22:ijms22031475. [PMID: 33540627 PMCID: PMC7867234 DOI: 10.3390/ijms22031475] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 01/29/2021] [Accepted: 01/29/2021] [Indexed: 12/02/2022] Open
Abstract
In this study, we found that the loss of OmpR, the response regulator of the two-component EnvZ/OmpR system, increases the cellular level of Fur, the master regulator of iron homeostasis in Y. enterocolitica. Furthermore, we demonstrated that transcription of the fur gene from the YePfur promoter is subject to negative OmpR-dependent regulation. Four putative OmpR-binding sites (OBSs) were indicated by in silico analysis of the fur promoter region, and their removal affected OmpR-dependent fur expression. Moreover, OmpR binds specifically to the predicted OBSs which exhibit a distinct hierarchy of binding affinity. Finally, the data demonstrate that OmpR, by direct binding to the promoters of the fecA, fepA and feoA genes, involved in the iron transport and being under Fur repressor activity, modulates their expression. It seems that the negative effect of OmpR on fecA and fepA transcription is sufficient to counteract the indirect, positive effect of OmpR resulting from decreasing the Fur repressor level. The expression of feoA was positively regulated by OmpR and this mode of action seems to be direct and indirect. Together, the expression of fecA, fepA and feoA in Y. enterocolitica has been proposed to be under a complex mode of regulation involving OmpR and Fur regulators.
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13
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Kelley BR, Lu J, Haley KP, Gaddy JA, Johnson JG. Metal homeostasis in pathogenic Epsilonproteobacteria: mechanisms of acquisition, efflux, and regulation. Metallomics 2021; 13:mfaa002. [PMID: 33570133 PMCID: PMC8043183 DOI: 10.1093/mtomcs/mfaa002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 11/25/2020] [Accepted: 12/03/2020] [Indexed: 12/14/2022]
Abstract
Epsilonproteobacteria are a diverse class of eubacteria within the Proteobacteria phylum that includes environmental sulfur-reducing bacteria and the human pathogens, Campylobacter jejuni and Helicobacter pylori. These pathogens infect and proliferate within the gastrointestinal tracts of multiple animal hosts, including humans, and cause a variety of disease outcomes. While infection of these hosts provides nutrients for the pathogenic Epsilonproteobacteria, many hosts have evolved a variety of strategies to either sequester metals from the invading pathogen or exploit the toxicity of metals and drive their accumulation as an antimicrobial strategy. As a result, C. jejuni and H. pylori have developed mechanisms to sense changes in metal availability and regulate their physiology in order to respond to either metal limitation or accumulation. In this review, we will discuss the challenges of metal availability at the host-pathogen interface during infection with C. jejuni and H. pylori and describe what is currently known about how these organisms alter their gene expression and/or deploy bacterial virulence factors in response to these environments.
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Affiliation(s)
- Brittni R Kelley
- Department of Microbiology, University of Tennessee, Knoxville, TN, USA
| | - Jacky Lu
- Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA
| | - Kathryn P Haley
- Department of Biology, Grand Valley State University, Grand Rapids, MI, USA
| | - Jennifer A Gaddy
- Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA
- Tennessee Valley Healthcare Systems, Department of Veterans Affairs, Nashville, TN, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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14
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Singh R, Ranaivoarisoa TO, Gupta D, Bai W, Bose A. Genetic Redundancy in Iron and Manganese Transport in the Metabolically Versatile Bacterium Rhodopseudomonas palustris TIE-1. Appl Environ Microbiol 2020; 86:e01057-20. [PMID: 32503905 PMCID: PMC7414945 DOI: 10.1128/aem.01057-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 05/31/2020] [Indexed: 12/24/2022] Open
Abstract
The purple nonsulfur bacterium Rhodopseudomonas palustris TIE-1 can produce useful biochemicals such as bioplastics and biobutanol. Production of such biochemicals requires intracellular electron availability, which is governed by the availability and the transport of essential metals such as iron (Fe). Because of the distinct chemical properties of ferrous [Fe(II)] and ferric iron [Fe(III)], different systems are required for their transport and storage in bacteria. Although Fe(III) transport systems are well characterized, we know much less about Fe(II) transport systems except for the FeoAB system. Iron transporters can also import manganese (Mn). We studied Fe and Mn transport by five putative Fe transporters in TIE-1 under metal-replete, metal-depleted, oxic, and anoxic conditions. We observed that by overexpressing feoAB, efeU, and nramp1AB, the intracellular concentrations of Fe and Mn can be enhanced in TIE-1 under oxic and anoxic conditions, respectively. The deletion of a single gene/operon does not attenuate Fe or Mn uptake in TIE-1 regardless of the growth conditions used. This indicates that genetically dissimilar yet functionally redundant Fe transporters in TIE-1 can complement each other. Relative gene expression analysis shows that feoAB and efeU are expressed during Fe and Mn depletion under both oxic and anoxic conditions. The promoters of these transporter genes contain a combination of Fur and Fnr boxes, suggesting that their expression is regulated by both Fe and oxygen availability. The findings from this study will help us modulate intracellular Fe and Mn concentrations, ultimately improving TIE-1's ability to produce desirable biomolecules.IMPORTANCERhodopseudomonas palustris TIE-1 is a metabolically versatile bacterium that can use various electron donors, including Fe(II) and poised electrodes, for photoautotrophic growth. TIE-1 can produce useful biomolecules, such as biofuels and bioplastics, under various growth conditions. Production of such reduced biomolecules is controlled by intracellular electron availability, which, in turn, is mediated by various iron-containing proteins in the cell. Several putative Fe transporters exist in TIE-1's genome. Some of these transporters can also transport Mn, part of several important cellular enzymes. Therefore, understanding the ability to transport and respond to various levels of Fe and Mn under different conditions is important to improve TIE-1's ability to produce useful biomolecules. Our data suggest that by overexpressing Fe transporter genes via plasmid-based expression, we can increase the import of Fe and Mn in TIE-1. Future work will leverage these data to improve TIE-1 as an attractive microbial chassis and future biotechnological workhorse.
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Affiliation(s)
- Rajesh Singh
- Department of Biology, Washington University in St. Louis, St. Louis, Missouri, USA
| | | | - Dinesh Gupta
- Department of Biology, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Wei Bai
- Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Arpita Bose
- Department of Biology, Washington University in St. Louis, St. Louis, Missouri, USA
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15
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Rahman YA, Ahmed LAW, Hafez RMM, Ahmed RMM. Helicobacter pylori and its hematological effect. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_103_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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16
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Han B, Zhang Z, Xie Y, Hu X, Wang H, Xia W, Wang Y, Li H, Wang Y, Sun H. Multi-omics and temporal dynamics profiling reveal disruption of central metabolism in Helicobacter pylori on bismuth treatment. Chem Sci 2018; 9:7488-7497. [PMID: 30510674 PMCID: PMC6223348 DOI: 10.1039/c8sc01668b] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 07/23/2018] [Indexed: 12/13/2022] Open
Abstract
Integration of multi-omics enables uncovering cellular responses to stimuli or the mechanism of action of a drug at a system level. Bismuth drugs have long been used for the treatment of Helicobacter pylori infection and their antimicrobial activity was attributed to dysfunction of multiple proteins based on previous proteome-wide studies. Herein, we investigated the response of H. pylori to a bismuth drug at transcriptome and metabolome levels. Our multi-omics data together with bioassays comprehensively reveal the impact of bismuth on a diverse array of intracellular pathways, in particular, disruption of central carbon metabolism is systematically evaluated as a primary bismuth-targeting system in H. pylori. Through temporal dynamics profiling, we demonstrate that bismuth initially perturbs the TCA cycle and then urease activity, followed by the induction of oxidative stress and inhibition of energy production, and in the meantime, induces extensive down-regulation in H. pylori metabolome. The present study thus expands our knowledge on the inhibitory actions of bismuth and provides a novel systematic perspective of H. pylori in response to a clinical drug that sheds light on enhanced therapeutic methodologies.
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Affiliation(s)
- Bingjie Han
- School of Chemistry , Sun Yat-sen University , Guangzhou , 510275 , P. R. China .
| | - Zhen Zhang
- School of Chemistry , Sun Yat-sen University , Guangzhou , 510275 , P. R. China .
| | - Yanxuan Xie
- School of Chemistry , Sun Yat-sen University , Guangzhou , 510275 , P. R. China .
| | - Xuqiao Hu
- Department of Chemistry , The University of Hong Kong , Hong Kong , P. R. China .
| | - Haibo Wang
- Department of Chemistry , The University of Hong Kong , Hong Kong , P. R. China .
| | - Wei Xia
- School of Chemistry , Sun Yat-sen University , Guangzhou , 510275 , P. R. China .
| | - Yulan Wang
- CAS Key Laboratory of Magnetic Resonance in Biological Systems , State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics , Wuhan Institute of Physics and Mathematics , Chinese Academy of Sciences , Wuhan , 430071 , P. R. China
| | - Hongyan Li
- Department of Chemistry , The University of Hong Kong , Hong Kong , P. R. China .
| | - Yuchuan Wang
- School of Chemistry , Sun Yat-sen University , Guangzhou , 510275 , P. R. China .
| | - Hongzhe Sun
- School of Chemistry , Sun Yat-sen University , Guangzhou , 510275 , P. R. China .
- Department of Chemistry , The University of Hong Kong , Hong Kong , P. R. China .
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Cao K, Zhang J, Miao XY, Wei QX, Zhao XL, He QY, Sun X. Evolution and molecular mechanism of PitAs in iron transport of Streptococcus species. J Inorg Biochem 2018; 182:113-123. [PMID: 29455001 DOI: 10.1016/j.jinorgbio.2018.02.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 02/05/2018] [Accepted: 02/07/2018] [Indexed: 12/24/2022]
Abstract
Iron is an essential element for almost all bacteria. The iron ATP-binding cassette (ABC) transporters located on the cell membrane affects bacterial virulence and infection. Although a variety of Fe3+-transporters have been found in bacteria, their evolutionary processes are rarely studied. Pneumococcal iron ABC transporter (PitA), a highly conserved Fe3+-transporter in most pathogenic bacteria, influences the capsule formation and virulence of bacteria. However, multiple sequence alignment revealed that PitA is expressed in four different variants in bacteria, and the structural complexity of these variants increases progressively. To more efficiently import Fe3+ ions into bacterial cells, bacteria have evolved a fused PitA from two separately expressed PitA-1 (SPD_0227) and PitA-2 (SPD_0226) proteins. Further biochemical characterization indicated that both PitA-1 and PitA-2 have weaker Fe3+-binding ability than their protein complex. More importantly, Glutathione S-Transferase (GST) pull-down and isothermal titration calorimetry (ITC) detection showed that PitA-1 and PitA-2 interact with each other via Tyr111-Leu37, Asn112-Gln38, Asn103-Leu33, and Asn103-Thr34. Further molecular dynamics (MD) simulations demonstrated that this interaction in full-length PitA is stronger than that in the two individual proteins. Deletion of PitA family genes could lead to decrease in the ability of iron acquisition and of adhesion and invasion of S. pneumoniae. Our study revealed the evolving state and molecular mechanism of Fe3+-transporter PitAs in bacteria and provided important information for understanding the iron transportation mechanism in bacteria and designing new antibacterial drugs.
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Affiliation(s)
- Kun Cao
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
| | - Jing Zhang
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
| | - Xin-Yu Miao
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
| | - Qiu-Xia Wei
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
| | - Xin-Lu Zhao
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
| | - Qing-Yu He
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
| | - Xuesong Sun
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
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18
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Karachaliou M, Chatzi L, Michel A, Kyriklaki A, Kampouri M, Koutra K, Roumeliotaki T, Chalkiadaki G, Stiakaki E, Pawlita M, Waterboer T, Kogevinas M, de Sanjose S. Helicobacter pylori Seropositivity and Childhood Neurodevelopment, the Rhea Birth Cohort in Crete, Greece. Paediatr Perinat Epidemiol 2017. [PMID: 28640520 DOI: 10.1111/ppe.12374] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Limited evidence exists on the association between exposure to Helicobacter pylori infection early in life, including fetal life, and neurodevelopment in childhood. METHODS We used prospective data on 352 mother-child pairs and cross-sectional data on 674 children to assess the association of maternal and child's H. pylori seropositivity correspondingly on child's neurodevelopment at age four in the Rhea birth cohort in Crete, Greece. Blood levels of immunoglobulin G antibodies to 12 H. pylori proteins were measured using multiplex serology. Child's neurodevelopment at age four was assessed using the McCarthy Scales of Children's Abilities. Linear regression models were used to explore the associations after adjusting for potential confounders. RESULTS Helicobacter pylori seroprevalence (95% CI) in cord blood, representing maternal status, was 41.5% (36.3%, 46.8%) and in 4 years old children was 6.5% (95% CI 4.8%, 8.7%). Children of H. pylori seropositive mothers had lower score in the general cognitive (-3.87, 95% CI -7.02, -0.72), verbal (-2.96, 95% CI -6.08, 0.15), perceptual performance (-3.37, 95% CI -6.60, -0.15), quantitative (-2.85, 95% CI -6.28, 0.58), and memory scale (-3.37, 95% CI -6.67, -0.07) compared to those of seronegative mothers. Seropositivity in cord blood specifically to GroEl and NapA - two of the 12 H. pylori proteins investigated - was associated with lower scores in almost all scales. At age four, H. pylori seropositive children performed worst in neurodevelopment assessment compared to their seronegative counterparts although no association reached statistically significant level. CONCLUSIONS Helicobacter pylori infection in early life may be an important but preventable risk factor for poor neurodevelopment.
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Affiliation(s)
- Marianna Karachaliou
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Leda Chatzi
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Angelika Michel
- Molecular Diagnostics of Oncogenic Infections Department, Infection and Cancer Programme, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Andriani Kyriklaki
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Mariza Kampouri
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Katerina Koutra
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Theano Roumeliotaki
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Georgia Chalkiadaki
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Eftichia Stiakaki
- Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Greece
| | - Michael Pawlita
- Molecular Diagnostics of Oncogenic Infections Department, Infection and Cancer Programme, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tim Waterboer
- Molecular Diagnostics of Oncogenic Infections Department, Infection and Cancer Programme, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Manolis Kogevinas
- Instituto de Salud Global Barcelona Barcelona, Catalunya, Spain.,Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Silvia de Sanjose
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.,Cancer Epidemiology Research Programme, Catalan Institute of Oncology, L'Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain
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19
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Romero-Espejel ME, Rodríguez MA, Chávez-Munguía B, Ríos-Castro E, Olivares-Trejo JDJ. Characterization of Spbhp-37, a Hemoglobin-Binding Protein of Streptococcus pneumoniae. Front Cell Infect Microbiol 2016; 6:47. [PMID: 27200302 PMCID: PMC4854876 DOI: 10.3389/fcimb.2016.00047] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 04/12/2016] [Indexed: 01/05/2023] Open
Abstract
Streptococcus pneumoniae is a Gram-positive microorganism that is the cause of bacterial pneumonia, sinusitis and otitis media. This human pathogen also can cause invasive diseases such as meningitis, bacteremia and septicemia. Hemoglobin (Hb) and haem can support the growth and viability of S. pneumoniae as sole iron sources. Unfortunately, the acquisition mechanism of Hb and haem in this bacterium has been poorly studied. Previously we identified two proteins of 37 and 22 kDa as putative Hb- and haem-binding proteins (Spbhp-37 and Spbhp-22, respectively). The sequence of Spbhp-37 protein was database annotated as lipoprotein without any function or localization. Here it was immunolocalized in the surface cell by transmission electron microscopy using specific antibodies produced against the recombinant protein. The expression of Spbhp-37 was increased when bacteria were grown in media culture supplied with Hb. In addition, the affinity of Sphbp-37 for Hb was determined. Thus, in this work we are presenting new findings that attempt to explain the mechanism involved in iron acquisition of this pathogen. In the future these results could help to develop new therapy targets in order to avoid the secondary effects caused by the traditional therapies.
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Affiliation(s)
- María E Romero-Espejel
- Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN México, México
| | - Mario A Rodríguez
- Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN México, México
| | - Bibiana Chávez-Munguía
- Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN México, México
| | - Emmanuel Ríos-Castro
- Unidad de Genómica, Proteómica y Metabolómica. LaNSE-CINVESTAV, Centro de Investigación y de Estudios Avanzados del IPN México, México
| | - José de Jesús Olivares-Trejo
- Laboratorio de Bacteriología y Nanomedicina, Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México México, México
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20
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Sekine Y, Tanzawa T, Tanaka Y, Ishimori K, Uchida T. Cytoplasmic Heme-Binding Protein (HutX) from Vibrio cholerae Is an Intracellular Heme Transport Protein for the Heme-Degrading Enzyme, HutZ. Biochemistry 2016; 55:884-93. [DOI: 10.1021/acs.biochem.5b01273] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Yukari Sekine
- Graduate
School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan
| | - Takehito Tanzawa
- Graduate
School of Life Science, Hokkaido University, Sapporo 060-0810, Japan
| | - Yoshikazu Tanaka
- Faculty
of Advanced Life Science, Hokkaido University, Sapporo 060-0810, Japan
- PRESTO, Japan Science and Technology Agency, Sapporo 060-0810, Japan
| | - Koichiro Ishimori
- Graduate
School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan
- Department
of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
| | - Takeshi Uchida
- Graduate
School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan
- Department
of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
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21
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Lau CKY, Krewulak KD, Vogel HJ. Bacterial ferrous iron transport: the Feo system. FEMS Microbiol Rev 2015; 40:273-98. [PMID: 26684538 DOI: 10.1093/femsre/fuv049] [Citation(s) in RCA: 238] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2015] [Indexed: 01/24/2023] Open
Abstract
To maintain iron homeostasis within the cell, bacteria have evolved various types of iron acquisition systems. Ferric iron (Fe(3+)) is the dominant species in an oxygenated environment, while ferrous iron (Fe(2+)) is more abundant under anaerobic conditions or at low pH. For organisms that must combat oxygen limitation for their everyday survival, pathways for the uptake of ferrous iron are essential. Several bacterial ferrous iron transport systems have been described; however, only the Feo system appears to be widely distributed and is exclusively dedicated to the transport of iron. In recent years, many studies have explored the role of the FeoB and FeoA proteins in ferrous iron transport and their contribution toward bacterial virulence. The three-dimensional structures for the Feo proteins have recently been determined and provide insight into the molecular details of the transport system. A highly select group of bacteria also express the FeoC protein from the same operon. This review will provide a comprehensive look at the structural and functional aspects of the Feo system. In addition, bioinformatics analyses of the feo operon and the Feo proteins have been performed to complement our understanding of this ubiquitous bacterial uptake system, providing a new outlook for future studies.
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Affiliation(s)
- Cheryl K Y Lau
- Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
| | - Karla D Krewulak
- Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
| | - Hans J Vogel
- Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, T2N 1N4, Canada
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Emiralioglu N, Yenicesu I, Sari S, Egritas O, Poyraz A, Pasaoglu OT, Celik B, Dalgic B. An insight into the relationships between prohepcidin, iron deficiency anemia, and interleukin-6 values in pediatric Helicobacter pylori gastritis. Eur J Pediatr 2015; 174:903-910. [PMID: 25567795 DOI: 10.1007/s00431-014-2482-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2014] [Revised: 10/21/2014] [Accepted: 11/21/2014] [Indexed: 02/08/2023]
Abstract
UNLABELLED The link between Helicobacter pylori and iron deficiency (ID) or iron deficiency anemia (IDA) has been investigated recently. We suggested that IDA/ID associated with H. pylori infection might be mediated by inflammation-driven hepcidin production. Patients with complaints of recurrent abdominal pain and dyspepsia aged between 7-16 years were included in this study. Patients were divided into two groups according to H. pylori status in upper gastrointestinal endoscopy. Group I who had H. pylori gastritis (n=50) received triple antibiotic therapy. Group II (n=50) who had H. pylori-negative gastritis only received proton pump inhibitor. Thirty healthy children with the similar age and gender were included in the study as a control group. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, prohepcidin and interleukin-6 (IL-6) values were evaluated in all children at the first visit. Initial tests were repeated after H. pylori eradication. Initial levels of ferritin (p=0.002), prohepcidin (p=0.003), and IL-6 (p=0.004) were found significantly lower in group I compared to group II and the control group. The mean prohepcidin level was lower in the anemic H. pylori-positive group than in non-anemic H. pylori-positive group; however, the difference was not statistically significant. While significant increases in hematocrit and mean corpuscular volume were observed, no significant difference was found in serum ferritin, prohepcidin, or IL-6 level after eradication treatment in H. pylori-positive group. CONCLUSION H. pylori-induced gastritis appears to cause an increase in prohepcidin levels and a decrease in ferritin levels, supporting our hypothesis; but this relationship has not been proven.
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Affiliation(s)
- Nagehan Emiralioglu
- Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara, Turkey,
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Abstract
Gram-positive Streptococcus species are responsible for millions of cases of meningitis, bacterial pneumonia, endocarditis, erysipelas and necrotizing fasciitis. Iron is essential for the growth and survival of Streptococcus in the host environment. Streptococcus species have developed various mechanisms to uptake iron from an environment with limited available iron. Streptococcus can directly extract iron from host iron-containing proteins such as ferritin, transferrin, lactoferrin and hemoproteins, or indirectly by relying on the employment of specialized secreted hemophores (heme chelators) and small siderophore molecules (high affinity ferric chelators). This review presents the most recent discoveries in the iron acquisition system of Streptococcus species - the transporters as well as the regulators.
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Affiliation(s)
- Ruiguang Ge
- Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Biocontrol, College of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
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Campuzano-Maya G. Hematologic manifestations of Helicobacter pylori infection. World J Gastroenterol 2014; 20:12818-12838. [PMID: 25278680 PMCID: PMC4177465 DOI: 10.3748/wjg.v20.i36.12818] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2014] [Revised: 06/10/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases.
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Pathak A, Blair VL, Ferrero RL, Mehring M, Andrews PC. Bismuth(iii) benzohydroxamates: powerful anti-bacterial activity against Helicobacter pylori and hydrolysis to a unique Bi34 oxido-cluster [Bi34O22(BHA)22(H-BHA)14(DMSO)6]. Chem Commun (Camb) 2014; 50:15232-4. [DOI: 10.1039/c4cc07329k] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Bismuth(iii) benzohydroxamates; [Bi2(HBA)3], [Bi(H-BHA)3], [Bi(HBA)(H-HBA)] and [Bi34O22(BHA)22(H-BHA)14(DMSO)6], all show exceptional toxicity towards Helicobacter pylori (MIC 0.08–3.24 μM).
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Affiliation(s)
- Amita Pathak
- School of Chemistry
- Monash University
- Melbourne, Australia
| | | | - Richard L. Ferrero
- MIMR-PHI Institute of Medical Research
- Centre for Innate Immunity and Infectious Diseases Monash University
- Melbourne, Australia
| | - Michael Mehring
- Fakultät für Naturwissenschaften
- Institut für Chemie
- Professur Koordinationschemie
- Technische Universität Chemnitz
- 09107 Chemnitz, Germany
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26
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Queiroz DMM, Rocha AMC, Crabtree JE. Unintended consequences of Helicobacter pylori infection in children in developing countries: iron deficiency, diarrhea, and growth retardation. Gut Microbes 2013; 4:494-504. [PMID: 23988829 PMCID: PMC3928161 DOI: 10.4161/gmic.26277] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Helicobacter pylori infection is predominantly acquired early in life. The prevalence of the infection in childhood is low in developed countries, whereas in developing countries most children are infected by 10 y of age. In poor resource settings, where malnutrition, parasitic/enteropathogen and H. pylori infection co-exist in young children, H. pylori might have potentially more diverse clinical outcomes. This paper reviews the impact of childhood H. pylori infection in developing countries that should now be the urgent focus of future research. The extra-gastric manifestations in early H. pylori infection in infants in poor resource settings might be a consequence of the infection associated initial hypochlorhydria. The potential role of H. pylori infection on iron deficiency, growth impairment, diarrheal disease, malabsorption and cognitive function is discussed in this review.
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Affiliation(s)
- Dulciene MM Queiroz
- Laboratory of Research in Bacteriology; Faculdade de Medicina; Universidade Federal de Minas Gerais; Belo Horizonte, Brazil
| | - Andreia MC Rocha
- Laboratory of Research in Bacteriology; Faculdade de Medicina; Universidade Federal de Minas Gerais; Belo Horizonte, Brazil
| | - Jean E Crabtree
- Leeds Institute Molecular Medicine; St. James’s University Hospital; University of Leeds; Leeds, UK,Correspondence to: Jean E Crabtree,
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27
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Abstract
Gastric adenocarcinoma is a leading cause of cancer-related death worldwide, and Helicobacter pylori infection is one of the strongest known risk factors for this malignancy. H. pylori strains exhibit a high level of genetic diversity, and the risk of gastric cancer is higher in persons carrying certain strain types (for example, those that contain a cag pathogenicity island or type s1 vacA alleles) than in persons carrying other strain types. Additional risk factors for gastric cancer include specific human genetic polymorphisms and specific dietary preferences (for example, a high-salt diet or a diet deficient in fruits and vegetables). Finally, iron-deficiency anemia is a risk factor for gastric cancer. Recent studies have provided evidence that several dietary risk factors for gastric cancer directly impact H. pylori virulence. In this review article, we discuss mechanisms by which diet can modulate H. pylori virulence and thereby influence gastric cancer risk.
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Affiliation(s)
- Timothy L Cover
- Division of Infectious Diseases; Vanderbilt University School of Medicine; Nashville, TN USA,Department of Pathology, Microbiology, and Immunology; Vanderbilt University School of Medicine; Nashville, TN USA,Veterans Affairs Tennessee Valley Healthcare System; Nashville, TN USA
| | - Richard M Peek, Jr
- Division of Gastroenterology, Department of Medicine; Vanderbilt University School of Medicine; Nashville, TN USA,Correspondence to: Richard M Peek, Jr,
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Serum hepcidin levels in Helicobacter pylori-infected children with iron-deficiency anemia: a case-control study. Ann Hematol 2013; 92:1477-83. [PMID: 23760782 DOI: 10.1007/s00277-013-1813-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2013] [Accepted: 06/04/2013] [Indexed: 12/13/2022]
Abstract
Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of systemic iron homeostasis. Hepcidin integrates signals from diverse physiological inputs, forming a key connection between iron trafficking and response to infection. In this study, we aimed to investigate whether Helicobacter pylori infection modulates serum hepcidin level and response to oral iron therapy in children with iron-deficiency anemia. This was a case-control study including 60 children with iron-deficiency anemia (IDA; 30 H. pylori infected and 30 H. pylori noninfected) and 30 healthy children with comparable age and gender as the control group. Iron parameters including serum iron, ferritin, transferrin, total iron binding capacity, and transferrin saturation and serum hepcidin levels were assessed initially and after 3 months of oral iron therapy for IDA. Compared to the control group, serum hepcidin was significantly lower in H. pylori-noninfected children with IDA (P < 0.01) and significantly higher in H. pylori-infected children with IDA (P < 0.01). Hepcidin increased significantly in noninfected children with IDA after 3 months of oral iron therapy (P < 0.01). On the other hand, H. pylori-infected children showed nonsignificant change in hepcidin level after oral iron therapy (P > 0.05). Although hepcidin showed significant positive correlations with serum ferritin, hemoglobin (Hb), iron, and transferrin saturation in noninfected children with IDA (P < 0.01), it showed significant negative correlations with serum ferritin, Hb, iron, and transferrin saturation in H. pylori-infected children with IDA (P < 0.05). H. pylori infection upregulates serum hepcidin levels and was associated with diminished response to oral iron therapy in children with iron-deficiency anemia.
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Li H, Song JB, Zhao WT, Yang ZM. AtHO1 is Involved in Iron Homeostasis in an NO-Dependent Manner. ACTA ACUST UNITED AC 2013; 54:1105-17. [DOI: 10.1093/pcp/pct063] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
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Yokota SI, Toita N, Yamamoto S, Fujii N, Konno M. Positive relationship between a polymorphism in Helicobacter pylori neutrophil-activating protein a gene and iron-deficiency anemia. Helicobacter 2013; 18:112-6. [PMID: 23067298 DOI: 10.1111/hel.12011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Numerous studies have suggested a link between iron-deficiency anemia (IDA) and Helicobacter pylori infection. Previously, we found that strains isolated from IDA patients showed higher levels of Fe ion uptake and Fe-ion-dependent rapid proliferation than those of strains derived from patients without IDA. MATERIALS AND METHODS Twenty-four H. pylori strains from IDA patients (IDA strains) and 25 strains from patients who had H. pylori gastritis without anemia (non-IDA strains) were examined. Their nucleotide sequences of napA, fur, and feoB, which contribute to Fe ion uptake, were determined. RESULTS Numerous polymorphisms of the three genes were found in both strains. Frequency of neutrophil-activating protein A (NapA), which encoded by napA, with threonine at amino acid residue No. 70 (Thr70-type NapA) was significantly higher in IDA strains than in non-IDA strains. Strains with Thr70-type NapA showed significantly higher levels of Fe(3+) and Fe(2+) uptake than did strains with other types, Ser70-type of NapA, which is found in standard strains. Other significantly different occurrences of polymorphisms between IDA and non-IDA groups were not observed in these genes. CONCLUSION The results suggest that H. pylori strains with Thr70-type NapA have enhanced Fe ion uptake ability and are associated with the pathogenesis of IDA.
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Affiliation(s)
- Shin-Ichi Yokota
- Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan
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Wang Z, Zhang L, Guo Z, Liu L, Ji J, Zhang J, Chen X, Liu B, Zhang J, Ding Q, Wang X, Zhao W, Zhu Z, Yu Y. A unique feature of iron loss via close adhesion of Helicobacter pylori to host erythrocytes. PLoS One 2012. [PMID: 23185604 PMCID: PMC3503993 DOI: 10.1371/journal.pone.0050314] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Iron deficiency anemia is an extra-stomach disease experienced in H. pylori carriers. Individuals with type A blood are more prone to suffering from H. pylori infection than other individuals. To clarify the molecular mechanisms underlying H. pylori-associated anemia, we collected erythrocytes from A, B, O, and AB blood donors and analyzed morphology, the number of erythrocytes with H. pylori colonies attached to them, and iron contents in erythrocytes and H. pylori (NCTC11637 and SS1 strains) by means of optical microscopy, scanning electron microscopy, and synchrotron radiation soft X-ray imaging. The number of type A erythrocytes with H. pylori attached to them was significantly higher than that of other erythrocytes (P<0.05). Far more iron distribution was observed in H. pylori bacteria using dual energy analysis near the iron L2, 3 edges by soft X-ray imaging. Iron content was significantly reduced in host erythrocytes after 4 hours of exposure to H. pylori. H. pylori are able to adhere more strongly to type A erythrocytes, and this is related to iron shift from the host to the bacteria. This may explain the reasons for refractory iron deficiency anemia and elevated susceptibility to H. pylori infection in individuals with type A blood.
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Affiliation(s)
- Zhiwei Wang
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lijuan Zhang
- Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai, China
| | - Zhi Guo
- Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai, China
| | - Lei Liu
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Ji
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianian Zhang
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuehua Chen
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bingya Liu
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Zhang
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiulan Ding
- Department of Transfusion and Clinical Biochemistry, Shanghai Ruijin Hospital, Shanghai, China
| | - Xuefeng Wang
- Department of Transfusion and Clinical Biochemistry, Shanghai Ruijin Hospital, Shanghai, China
| | - Wei Zhao
- Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenggang Zhu
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- * E-mail: (YY); (ZZ)
| | - Yingyan Yu
- Shanghai Institute of Digestive Surgery and Department of Surgery, Shanghai Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- * E-mail: (YY); (ZZ)
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