The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD.
The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD.
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DOI：
10.1038/ncomms8996
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发表时间：
2015-08-18
影响因子：
16.6
通讯作者：
Moraes TF
中科院分区：
文献类型：
--
作者：
Calmettes C;Ing C;Buckwalter CM;El Bakkouri M;Chieh-Lin Lai C;Pogoutse A;Gray-Owen SD;Pomès R;Moraes TF
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. ZnuD is a conserved zinc transporter expressed in several bacterial pathogens with potential as a target against infection. Here the authors demonstrate a requirement for ZnuD in systemic infection by N. meningitidis and define the molecular mechanism of ZnuD-mediated Zinc transport across the bacterial outer membrane.
