The FupA/B protein uniquely facilitates transport of ferrous iron and siderophore-associated ferric iron across the outer membrane of Francisella tularensis live vaccine strain
Girija Ramakrishnan and Bhaswati Sen
Microbiology (Society for General Microbiology), v 160(2), pp 446-457
Life Sciences & Biomedicine Microbiology Science & Technology
Francisella tularensis is a highly infectious Gram-negative pathogen that replicates intracellularly within the mammalian host. One of the factors associated with virulence of F. tularensis is the protein FupA that mediates high-affinity transport of ferrous iron across the outer membrane. Together with its paralogue FsIE, a siderophore ferric iron transporter, FupA supports survival of the pathogen in the host by providing access to the essential nutrient iron. The FupA orthologue in the attenuated live vaccine strain (LVS) is encoded by the hybrid gene fupA/B, the product of an intergenic recombination event that significantly contributes to attenuation of the strain. We used Fe-55 transport assays with mutant strains complemented with the different paralogues to show that the FupA/B protein of LVS retains the capacity for high-affinity transport of ferrous iron, albeit less efficiently than FupA of virulent strain Schu S4. Fe-55 transport assays using purified siderophore and siderophore-dependent growth assays on iron-limiting agar confirmed previous findings that FupA/B also contributes to siderophore-mediated ferric iron uptake. These assays further demonstrated that the LVS FsIE protein is a weaker siderophore-ferric iron transporter than the orthologue from Schu S4, and may be a result of the sequence variation between the two proteins. Our results indicate that iron-uptake mechanisms in LVS differ from those in Schu S4 and that functional differences in the outer membrane iron transporters have distinct effects on growth under iron limitation.
The FupA/B protein uniquely facilitates transport of ferrous iron and siderophore-associated ferric iron across the outer membrane of Francisella tularensis live vaccine strain
Creators
Girija Ramakrishnan - University of Virginia
Bhaswati Sen - University of Virginia
Publication Details
Microbiology (Society for General Microbiology), v 160(2), pp 446-457
Publisher
Microbiology Soc
Number of pages
12
Grant note
University of Virginia School of Medicine
AI067823 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
R01AI067823 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
Resource Type
Journal article
Language
English
Academic Unit
Microbiology and Immunology
Web of Science ID
WOS:000338603100020
Scopus ID
2-s2.0-84893484153
Other Identifier
991019173958504721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool: