title: Changes of the phagosomal elemental concentrations by Mycobacterium tuberculosis Mramp.
abstract: Pathogenic mycobacteria survive within phagosomes which are thought to represent a nutrient-restricted environment. Divalent cation transporters of the Nramp family in phagosomes and mycobacteria (Mramp) may compete for metals that are crucial for bacterial survival. The elemental concentrations in phagosomes of macrophages infected with wild-type Mycobacterium tuberculosis (M. tuberculosis strain H37Rv) and a M. tuberculosis Mramp knockout mutant (Mramp-KO), derived from a clinical isolate isogenic to the strain MT103, were compared. Time points of 1 and 24 h after infection of mouse peritoneal macrophages (bcg(S)) were compared in both cases. Increased concentrations of P, Ni and Zn and reduced Cl concentration in Mramp-KO after 1 h of infection were observed, compared to M. tuberculosis vacuoles. After 24 h of infection, significant differences in the P, Cl and Zn concentrations were still present. The Mramp-KO phagosome showed a significant increase of P, Ca, Mn, Fe and Zn concentrations between 1 and 24 h after infection, while the concentrations of K and Ni decreased. In the M. tuberculosis vacuole, the Fe concentration showed a similar increase, while the Cl concentration decreased. The fact that the concentration of several divalent cations increased in the Mramp-KO strain suggests that Mramp may have no impact on the import of these divalent cations into the mycobacterium, but may function as a cation efflux pump. The concordant increase of Fe concentrations within M. tuberculosis, as well as within the Mramp-KO vacuoles, implies that Mramp, in contrast to siderophores, might not be important for the attraction of Fe and its retention in phagosomes of unstimulated macrophages.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Freiburg, Hugstetter Str 55, 79106 Freiburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wagner
authors.affiliation: Experimental Facilities, Argonne National Laboratory, Argonne, IL, USA.
authors.forename: Jörg
authors.initials: J
authors.lastname: Maser
authors.affiliation: Experimental Facilities, Argonne National Laboratory, Argonne, IL, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Moric
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
authors.forename: Neio
authors.initials: N
authors.lastname: Boechat
authors.affiliation: Experimental Facilities, Argonne National Laboratory, Argonne, IL, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vogt
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.affiliation: Experimental Facilities, Argonne National Laboratory, Argonne, IL, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Lai
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Reyrat
authors.affiliation: Department of Microbiology, College of Science, Oregon State University, Corvallis, OR, USA.|Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: Luiz
authors.initials: L
authors.lastname: Bermudez
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D017136:Ion Transport; D017737:Macrophages, Peritoneal / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D002413:Cations, Divalent