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Two parallel pathways for ferric and ferrous iron acquisition support growth and virulence of the intracellular pathogen Francisella tularensis Schu S4
Journal article   Open access   Peer reviewed

Two parallel pathways for ferric and ferrous iron acquisition support growth and virulence of the intracellular pathogen Francisella tularensis Schu S4

Natalie Pérez, Richard Johnson, Bhaswati Sen and Girija Ramakrishnan
MicrobiologyOpen (Weinheim), v 5(3), pp 453-468
Jun 2016
PMID: 26918301
url
https://doi.org/10.1002/mbo3.342View
Published, Version of Record (VoR) Open

Abstract

Animals Biological Transport - genetics Cation Transport Proteins - genetics Cation Transport Proteins - metabolism Copper - metabolism Ferric Compounds - metabolism Ferrous Compounds - metabolism Francisella tularensis - growth & development Francisella tularensis - metabolism Francisella tularensis - pathogenicity Gene Deletion Iron - metabolism Male Mice Mice, Inbred C57BL Micronutrients - metabolism Siderophores - genetics Siderophores - metabolism Tularemia - microbiology Tularemia - pathology
Iron acquisition mechanisms in Francisella tularensis, the causative agent of tularemia, include the Francisella siderophore locus (fsl) siderophore operon and a ferrous iron-transport system comprising outer-membrane protein FupA and inner-membrane transporter FeoB. To characterize these mechanisms and to identify any additional iron uptake systems in the virulent subspecies tularensis, single and double deletions were generated in the fsl and feo iron acquisition systems of the strain Schu S4. Deletion of the entire fsl operon caused loss of siderophore production that could be restored by complementation with the biosynthetic genes fslA and fslC and Major Facilitator Superfamily (MFS) transporter gene fslB. (55) Fe-transport assays demonstrated that siderophore-iron uptake required the receptor FslE and MFS transporter FslD. A ΔfeoB' mutation resulted in loss of ability to transport ferrous iron ((55) Fe(2+) ). A ΔfeoB' ΔfslA mutant that required added exogenous siderophore for growth in vitro was unable to grow within tissue culture cells and was avirulent in mice, indicating that no compensatory cryptic iron uptake systems were induced in vivo. These studies demonstrate that the fsl and feo pathways function independently and operate in parallel to effectively support virulence of F. tularensis.

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