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Identified Virulence Factors of Francisella : Iron uptake


FupA (Fe utilization protein A)  

Related genes: feoB; fupA;
Keywords: Iron uptake;
Characteristics:
FupA and FslE are paralogs belonging to a family of proteins unique to Francisella
Structure features:
Both FupA and FslE fold as β- barrels in the outer membrane with amino-terminal periplasmic domains
Figures:
Ferrous iron acquisition in F. tularensis (From: Ramakrishnan G, 2017. Iron and Virulence in Francisella tularensis. Front Cell Infect Microbiol 7:107.)

Functions:
High-affinity iron transport Protein involved in ferrous iron acquisition
References:
Twine S, et al., 2005. A mutant of Francisella tularensis strain SCHU S4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine. Infect Immun 73(12):8345-52.
Lindgren H, et al., 2009. The 58-kilodalton major virulence factor of Francisella tularensis is required for efficient utilization of iron. Infect Immun 77(10):4429-36.
Sen B, et al., 2010. The fslE homolog, FTL_0439 (fupA/B), mediates siderophore-dependent iron uptake in Francisella tularensis LVS. Infect Immun 78(10):4276-85.
Ramakrishnan G, et al., 2012. Paralogous outer membrane proteins mediate uptake of different forms of iron and synergistically govern virulence in Francisella tularensis tularensis. J Biol Chem 287(30):25191-202.
Thomas-Charles CA, et al., 2013. FeoB-mediated uptake of iron by Francisella tularensis. Infect Immun 81(8):2828-37.
Ramakrishnan G, et al., 2014. 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. Microbiology 160(Pt 2):446-57.
Perez N, et al., 2016. Two parallel pathways for ferric and ferrous iron acquisition support growth and virulence of the intracellular pathogen Francisella tularensis Schu S4. Microbiologyopen 5(3):453-68.
Ramakrishnan G, 2017. Iron and Virulence in Francisella tularensis. Front Cell Infect Microbiol 7:107.


Rhizoferrin  

Related genes: fslA; fslB; fslC; fslD; fslE;
Keywords: Iron uptake; Siderophore-dependent;
Figures:
Siderophore-mediated iron acquisition in F. tularensis (From: Ramakrishnan G, 2017. Iron and Virulence in Francisella tularensis. Front Cell Infect Microbiol 7:107.)

Functions:
Siderophore-mediated Iron acquisition
Mechanism:
Siderophore biosynthesis involves enzymes FslA and FslC, while export across the inner membrane is mediated by FslB. Uptake of the rhizoferrin- ferric iron complex is effected by the siderophore receptor FslE in the outer membrane in a TonB-independent process, and FslD is responsible for uptake across the inner membrane.
References:
Sullivan JT, et al., 2006. Characterization of the siderophore of Francisella tularensis and role of fslA in siderophore production. J Bacteriol 188(11):3785-95.
Huntley JF, et al., 2007. Characterization of Francisella tularensis outer membrane proteins. J Bacteriol 189(2):561-74.
Ramakrishnan G, et al., 2008. fslE is necessary for siderophore-mediated iron acquisition in Francisella tularensis Schu S4. J Bacteriol 190(15):5353-61.
Wehrly TD, et al., 2009. Intracellular biology and virulence determinants of Francisella tularensis revealed by transcriptional profiling inside macrophages. Cell Microbiol 11(7):1128-50.
Perez NM, et al., 2014. The reduced genome of the Francisella tularensis live vaccine strain (LVS) encodes two iron acquisition systems essential for optimal growth and virulence. PLoS One 9(4):e93558.
Perez N, et al., 2016. Two parallel pathways for ferric and ferrous iron acquisition support growth and virulence of the intracellular pathogen Francisella tularensis Schu S4. Microbiologyopen 5(3):453-68.








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