title: Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin.
abstract: Mycobacterium tuberculosis (M.tb), which requires iron for survival, acquires this element by synthesizing iron-binding molecules known as siderophores and by recruiting a host iron-transport protein, transferrin, to the phagosome. The siderophores extract iron from transferrin and transport it into the bacterium. Here we describe an additional mechanism for iron acquisition, consisting of an M.tb protein that drives transport of human holo-transferrin into M.tb cells. The pathogenic strain M.tb H37Rv expresses several proteins that can bind human holo-transferrin. One of these proteins is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH, Rv1436), which is present on the surface of M.tb and its relative Mycobacterium smegmatis. Overexpression of GAPDH results in increased transferrin binding to M.tb cells and iron uptake. Human transferrin is internalized across the mycobacterial cell wall in a GAPDH-dependent manner within infected macrophages.
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), Phase X, Sector 67, SAS Nagar, Punjab 160062, India.
authors.forename: Vishant Mahendra
authors.initials: VM
authors.lastname: Boradia
authors.affiliation: Institute of Microbial Technology (IMTECH), Sector 39A, Chandigarh 160036, India.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Malhotra
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), Phase X, Sector 67, SAS Nagar, Punjab 160062, India.
authors.forename: Janak Shrikant
authors.initials: JS
authors.lastname: Thakkar
authors.affiliation: 1] Institute of Microbial Technology (IMTECH), Sector 39A, Chandigarh 160036, India [2].
authors.forename: Vikas Ajit
authors.initials: VA
authors.lastname: Tillu
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), Phase X, Sector 67, SAS Nagar, Punjab 160062, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Vuppala
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), Phase X, Sector 67, SAS Nagar, Punjab 160062, India.
authors.forename: Pravinkumar
authors.initials: P
authors.lastname: Patil
authors.affiliation: Institute of Microbial Technology (IMTECH), Sector 39A, Chandigarh 160036, India.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Sheokand
authors.affiliation: 1] Institute of Microbial Technology (IMTECH), Sector 39A, Chandigarh 160036, India [2].
authors.forename: Prerna
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Institute of Microbial Technology (IMTECH), Sector 39A, Chandigarh 160036, India.
authors.forename: Anoop Singh
authors.initials: AS
authors.lastname: Chauhan
authors.affiliation: Institute of Microbial Technology (IMTECH), Sector 39A, Chandigarh 160036, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Raje
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), Phase X, Sector 67, SAS Nagar, Punjab 160062, India.
authors.forename: Chaaya Iyengar
authors.initials: CI
authors.lastname: Raje
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D005260:Female; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011817:Rabbits; D017262:Siderophores / Q000378:metabolism; D014168:Transferrin / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D017262:Siderophores; D014168:Transferrin; D007501:Iron; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)