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A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence

Neisseria meningitidis (Nm) and N. gonorrhoeae (Ng) are adapted to different environments within their human host. If the basis of this difference has not yet been fully understood, previous studies (including our own data) have reported that, unlike Ng, Nm tolerates high manganese concentrations. A...

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Autores principales: Veyrier, Frédéric J., Boneca, Ivo G., Cellier, Mathieu F., Taha, Muhamed-Kheir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182930/
https://www.ncbi.nlm.nih.gov/pubmed/21980287
http://dx.doi.org/10.1371/journal.ppat.1002261
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author Veyrier, Frédéric J.
Boneca, Ivo G.
Cellier, Mathieu F.
Taha, Muhamed-Kheir
author_facet Veyrier, Frédéric J.
Boneca, Ivo G.
Cellier, Mathieu F.
Taha, Muhamed-Kheir
author_sort Veyrier, Frédéric J.
collection PubMed
description Neisseria meningitidis (Nm) and N. gonorrhoeae (Ng) are adapted to different environments within their human host. If the basis of this difference has not yet been fully understood, previous studies (including our own data) have reported that, unlike Ng, Nm tolerates high manganese concentrations. As transition metals are essential regulators of cell growth and host pathogen interactions, we aimed to address mechanisms of Nm Mn(2+) tolerance and its pathogenic consequences. Using bioinformatics, gene deletion and heterologous expression we identified a conserved bacterial manganese resistance factor MntX (formerly YebN). The predicted structure suggests that MntX represents a new family of transporters exporting Mn. In the Neisseria genus, this exporter is present and functional in all Nm isolates but it is mutated in a majority of Ng strains and commonly absent in nonpathogenic species. In Nm, Mn(2+) export via MntX regulates the intracellular Mn/Fe ratio and protects against manganese toxicity that is exacerbated in low iron conditions. MntX is also important for N. meningitidis to resist killing by human serum and for survival in mice blood during septicemia. The present work thus points to new clues about Mn homeostasis, its interplay with Fe metabolism and the influence on N. meningitidis physiology and pathogenicity.
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spelling pubmed-31829302011-10-06 A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence Veyrier, Frédéric J. Boneca, Ivo G. Cellier, Mathieu F. Taha, Muhamed-Kheir PLoS Pathog Research Article Neisseria meningitidis (Nm) and N. gonorrhoeae (Ng) are adapted to different environments within their human host. If the basis of this difference has not yet been fully understood, previous studies (including our own data) have reported that, unlike Ng, Nm tolerates high manganese concentrations. As transition metals are essential regulators of cell growth and host pathogen interactions, we aimed to address mechanisms of Nm Mn(2+) tolerance and its pathogenic consequences. Using bioinformatics, gene deletion and heterologous expression we identified a conserved bacterial manganese resistance factor MntX (formerly YebN). The predicted structure suggests that MntX represents a new family of transporters exporting Mn. In the Neisseria genus, this exporter is present and functional in all Nm isolates but it is mutated in a majority of Ng strains and commonly absent in nonpathogenic species. In Nm, Mn(2+) export via MntX regulates the intracellular Mn/Fe ratio and protects against manganese toxicity that is exacerbated in low iron conditions. MntX is also important for N. meningitidis to resist killing by human serum and for survival in mice blood during septicemia. The present work thus points to new clues about Mn homeostasis, its interplay with Fe metabolism and the influence on N. meningitidis physiology and pathogenicity. Public Library of Science 2011-09-29 /pmc/articles/PMC3182930/ /pubmed/21980287 http://dx.doi.org/10.1371/journal.ppat.1002261 Text en Veyrier et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Veyrier, Frédéric J.
Boneca, Ivo G.
Cellier, Mathieu F.
Taha, Muhamed-Kheir
A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence
title A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence
title_full A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence
title_fullStr A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence
title_full_unstemmed A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence
title_short A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence
title_sort novel metal transporter mediating manganese export (mntx) regulates the mn to fe intracellular ratio and neisseria meningitidis virulence
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182930/
https://www.ncbi.nlm.nih.gov/pubmed/21980287
http://dx.doi.org/10.1371/journal.ppat.1002261
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