title: FeoB-mediated uptake of iron by Francisella tularensis.
abstract: Francisella tularensis, the bacterial cause of tularemia, infects the liver and replicates in hepatocytes in vivo and in vitro. However, the factors that govern adaptation of F. tularensis to the intrahepatocytic niche have not been identified. Using cDNA microarrays, we determined the transcriptional profile of the live vaccine strain (LVS) of F. tularensis grown in the FL83B murine hepatocytic cell line compared to that of F. tularensis cultured in broth. The fslC gene of the fsl operon was the most highly upregulated. Deletion of fslC eliminated the ability of the LVS to produce siderophore, which is involved in uptake of ferric iron, but it did not impair its growth in hepatocytes, A549 epithelial cells, or macrophages. Therefore, we sought an alternative means by which F. tularensis might obtain iron. Deletion of feoB, which encodes a putative ferrous iron transporter, retarded replication of the LVS in iron-restricted media, reduced its growth in hepatocytic and epithelial cells, and impaired its acquisition of iron. Survival of mice infected intradermally with a lethal dose of the LVS was slightly improved by deletion of fslC but was not altered by loss of feoB. However, the ΔfeoB mutant showed diminished ability to colonize the lungs, liver, and spleen of mice that received sublethal inocula. Thus, FeoB represents a previously unidentified mechanism for uptake of iron by F. tularensis. Moreover, failure to produce a mutant strain lacking both feoB and fslC suggests that FeoB and the proteins of the fsl operon are the only major means by which F. tularensis acquires iron.
authors.affiliation: Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Cindy A
authors.initials: CA
authors.lastname: Thomas-Charles
authors.forename: Huaixin
authors.initials: H
authors.lastname: Zheng
authors.forename: Lance E
authors.initials: LE
authors.lastname: Palmer
authors.forename: Patricio
authors.initials: P
authors.lastname: Mena
authors.forename: David G
authors.initials: DG
authors.lastname: Thanassi
authors.forename: Martha B
authors.initials: MB
authors.lastname: Furie
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D005604:Francisella tularensis / Q000378:metabolism*; D022781:Hepatocytes / Q000382:microbiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014406:Tularemia / Q000378:metabolism*; D014774:Virulence / Q000502:physiology
chemical_list: D027682:Cation Transport Proteins; D007501:Iron