title: A novel metal transporter mediating manganese export (MntX) regulates the Mn to Fe intracellular ratio and Neisseria meningitidis virulence.
abstract: 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.
authors: Institut Pasteur, Infection Bactériennes Invasives, Dept. Infection et Epidémiologie, Paris, France. frederic.veyrier@pasteur.fr
authors: Frédéric J
authors: FJ
authors: Veyrier
authors: Ivo G
authors: IG
authors: Boneca
authors: Mathieu F
authors: MF
authors: Cellier
authors: Muhamed-Kheir
authors: MK
authors: Taha
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D011994:Recombinant Proteins; D008345:Manganese; D007501:Iron