Competition for Iron Between Host and Pathogen: A Structural Case Study on Helicobacter pylori

Published on Jan 1, 2017in Methods of Molecular Biology
路 DOI :10.1007/978-1-4939-6673-8_5
Wei Xia18
Estimated H-index: 18
(SYSU: Sun Yat-sen University)
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Abstract
: Helicobacter pylori (H. pylori) is a highly successful bacterial pathogen, which colonizes the stomach of more than half of the world's population. To colonize and survive in such an acidic and inhospitable niche, H. pylori cells have evolved complex mechanisms to acquire nutrients from human hosts, including iron, an essential nutrient for both the pathogens and host cells. However, human cells also utilize diverse strategies in withholding of irons to prevent the bacterial outgrowth. The competition for iron is the central battlefield between pathogen and host. This mini-review summarizes the updated scenarios of the battle for iron between H. pylori and human host from a structural biology perspective.
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Over 300 Bi-binding peptides from 166 proteins in H. pylori were identified by Bi-IMAC. Bi3+ exhibits high selectivity towards peptide enriched by cysteines and histidines with dominated motif patterns of CXnC, CXnH and HXnH. Structural rationalization and functional categorization on the identified Bi-binding peptides and proteins provide an insight into the inhibitory action of bismuth drugs.
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Calprotectin sequesters manganese and zinc from bacteria, preventing their growth. Spectroscopic and biological data show it also chelates iron with sub-picomolar affinity using a hexahistidine motif, establishing a new mechanism for its antibacterial activity.
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#1Megan Brunjes Brophy (MIT: Massachusetts Institute of Technology)H-Index: 9
#2Elizabeth M. Nolan (MIT: Massachusetts Institute of Technology)H-Index: 42
Bacterial and fungal pathogens cause a variety of infectious diseases and constitute a significant threat to public health. The human innate immune system represents the first line of defense against pathogenic microbes and employs a range of chemical artillery to combat these invaders. One important mechanism of innate immunity is the sequestration of metal ions that are essential nutrients. Manganese is one nutrient that is required for many pathogens to establish an infective lifestyle. This ...
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Crohn鈥檚 disease and ulcerative colitis are characterized by periods of symptomatic relapse and remission. Diagnosis and assessment of inflammatory bowel disease has so far been based on clinical evaluation, serum parameters, radiology and endoscopy. Faecal markers such as calprotectin or lactoferrin have emerged as new diagnostic tools to detect and monitor intestinal inflammation. This review focuses on their potential clinical applications and limitations in the management of inflammatory bowe...
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#1Steven M. Damo (Vandy: Vanderbilt University)H-Index: 11
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The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed 鈥渘utritional immunity.鈥 CP binds Mn2+ and Zn2+ with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified the molecular basis of Mn2+ sequestration. The asymmetry of the CP heterodimer creates a single Mn2+-binding site from six histidine residues, which distinguishes CP from all other Mn2+...
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FrpB is an outer membrane transporter from Neisseria meningitidis, the causative agent of meningococcal meningitis. It is a member of the TonB-dependent transporter (TBDT) family and is responsible for iron uptake into the periplasm. FrpB is subject to a high degree of antigenic variation, principally through a region of hypervariable sequence exposed at the cell surface. From the crystal structures of two FrpB antigenic variants, we identify a bound ferric ion within the structure which induces...
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#1Nan Yang (HKU: University of Hong Kong)H-Index: 12
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structures exhibit unique 鈥樷榩artially-opened鈥欌 conformations between those of the apo-hTF and holo-hTF. Fe(III) and Bi(III) in the N-lobe coordinate to, besides anions, only two (Tyr95 and Tyr188) and one (Tyr188) tyrosine residues, respectively, in contrast to four residues in the holo-hTF. The C-lobe of both structures are fully closed with iron coordinating to four residues and a carbonate. The structures of hTF observed here represent key conformers captured in the dynamic nature of the tran...
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#2Eric P. Skaar (Vandy: Vanderbilt University)H-Index: 71
Vertebrates protect against infection through the sequestration of nutrient metals, and bacterial pathogens have evolved sophisticated acquisition strategies to circumvent this host defence. In this Review, Hood and Skaar describe this molecular arms race for nutrients.
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Summary In Helicobacter pylori, iron balance is controlled by the Ferric uptake regulator (Fur), an iron-sensing repressor protein that typically regulates expression of genes implicated in iron transport and storage. Herein, we carried out extensive analysis of Fur-regulated promoters and identified a 7-1-7 motif with dyad symmetry (5鈥-TAATAATnATTATTA-3鈥), which functions as the Fur box core sequence of H.聽pylori. Addition of this sequence to the promoter region of a typically non-Fur regulated...
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Copper is an essential element for all living organisms; however, it becomes toxic at high concentrations due to its ability to participate in many redox reactions. This vital micronutrient balance plays an important role in the battle between host and pathogen, due to its use by the host to intoxicate pathogens. In this study, we explore the effects of copper deprivation on Helicobacter infection in mice using the copper chelator tetrathiomolybdate. Our results reveal that Helicobacter infectio...
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