PMID (identifiant
de la référence Pubmed) : |
 |
 (21980287) |
|
| Titre : |
|
A novel metal transporter mediating manganese export (MntX) regulates the Mn to Fe intracellular ratio and Neisseria meningitidis virulence. |
|
| Auteur(s) : |
|
Frédéric J Veyrier ( ) 1, 2, 3, 4, Ivo G Boneca3, 4, Mathieu F Cellier1, Muhamed-Kheir Taha2 |
|
| Laboratoire : |
|
|
|
| Résumé : |
|
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 Mn²⁺ 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, Mn²⁺ 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. |
|
| Domaine : |
|
Sciences du Vivant/Microbiologie et Parasitologie/Bactériologie
|
|
Langue du texte
intégral : |
|
Anglais |
|
| : |
|
1553-7366 |
|
|
| Type de publication : |
|
Articles dans des revues avec comité de lecture |
|
| DOI : |
|
10.1371/journal.ppat.1002261 |
|
| Journal : |
|
|
|
| Audience : |
|
internationale |
|
| Date de publication : |
|
09/2011 |
|
Date de publication
électronique : |
|
29/09/2011 |
|
| Volume : |
|
7 |
|
| Numéro : |
|
9 |
|
| Page, identifiant, ... : |
|
e1002261 |
|
|
| Descripteur(s) MeSH : |
|
Animals – Bacterial Proteins – Carrier Proteins – Drug Resistance – Bacterial – Gene Deletion – Gene Expression – Humans – Ion Transport – Iron – Manganese – Mice – Inbred BALB C – Neisseria meningitidis – Recombinant Proteins – Virulence |
|
| Contrat, financement : |
|
FV was supported through a Marie Curie Excellence grant. This work was partially supported by a Discovery Grant from the Natural Sciences and Engineering Research council of Canada (MFMC, 203297-03) and by a grant from the ERA-NET PathoGenomics (ANR-08-PATH-003-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
|
