The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD

Invading bacteria from the Neisseriaceae, Acinetobacteriaceae, Bordetellaceae and Moraxellaceae families express the conserved outer-membrane zinc transporter zinc-uptake component D (ZnuD) to overcome nutritional restriction imposed by the host organism during infection. Here we demonstrate that Zn...

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Published in:Nature communications 2015-08, Vol.6 (1), p.7996-7996, Article 7996
Main Authors: Calmettes, Charles, Ing, Christopher, Buckwalter, Carolyn M, El Bakkouri, Majida, Chieh-Lin Lai, Christine, Pogoutse, Anastassia, Gray-Owen, Scott D, Pomès, Régis, Moraes, Trevor F
Format: Article
Language:English
Subjects:
Animals
Bacterial Outer Membrane Proteins - genetics
Bacterial Outer Membrane Proteins - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Cation Transport Proteins - genetics
Cation Transport Proteins - metabolism
Female
Gene Expression Regulation, Bacterial
Male
Mice
Mice, Inbred C57BL
Models, Molecular
Neisseria meningitidis - metabolism
Protein Conformation
Sepsis - microbiology
Zinc - metabolism
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creator Calmettes, Charles
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Moraes, Trevor F
description Invading bacteria from the Neisseriaceae, Acinetobacteriaceae, Bordetellaceae and Moraxellaceae families express the conserved outer-membrane zinc transporter zinc-uptake component D (ZnuD) to overcome nutritional restriction imposed by the host organism during infection. Here we demonstrate that ZnuD is required for efficient systemic infections by the causative agent of bacterial meningitis, Neisseria meningitidis, in a mouse model. We also combine X-ray crystallography and molecular dynamics simulations to gain insight into the mechanism of zinc recognition and transport across the bacterial outer-membrane by ZnuD. Because ZnuD is also considered a promising vaccine candidate against N. meningitidis, we use several ZnuD structural intermediates to map potential antigenic epitopes, and propose a mechanism by which ZnuD can maintain high sequence conservation yet avoid immune recognition by altering the conformation of surface-exposed loops.
doi_str_mv 10.1038/ncomms8996
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source Nature Open Access; Publicly Available Content Database; Springer Nature - Connect here FIRST to enable access; PubMed Central
subjects Animals
Bacterial Outer Membrane Proteins - genetics
Bacterial Outer Membrane Proteins - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Cation Transport Proteins - genetics
Cation Transport Proteins - metabolism
Female
Gene Expression Regulation, Bacterial
Male
Mice
Mice, Inbred C57BL
Models, Molecular
Neisseria meningitidis - metabolism
Protein Conformation
Sepsis - microbiology
Zinc - metabolism
title The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD
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