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Iron transport

Cuiv et al 2004 Discovery of rhtx rhizobactin transporter and then, by homology, fptX pyochelin transporter and used to carry iron across the inner membrane. Mutated genes out then readded them and showed rescue of siderophore-usage with narrower specificity.
Frederick et al 2009 Review, iron transport in therapeutics: Quinine and artemisinin both target malarial iron via heme. Bacteria can produce more siderophore mass than their own. Siderophores have high redundancy but often utilise common moieties, tagetting these may work
Goetz et al 2002 Human neutrophils produce siderocalin, bacteriostatic in low iron by siderophore sequestration. Uses x-ray crystal to show sequestration. Siderocalin cant bind iron without bacterial product
Pawelek et al 2006 Shows TonB bound to FhuA (outer membrane iron transporter). Uses x-ray crystallography. TonB spans the periplasm, powering the transporter by transmitting conformational changes driven by the proton motive force over the inner membrane.
Hu & Miller 1997 M. smegmatis uses a siderophore that is toxic to m. tuberculosis, the only difference bytween the siderophores used by each is the handedness of one stereocentre. Difficult to produce en masse but mimicking siderophores may be a good plan.
Donadio et al 1991 Description of poly-ketide synthases. Used to make things like fatty acids but can also be used to generate microbial antibiotics, immunosuppressants and siderophores without a genetic template.
Marahiel et al 1997 Review describing modular (multiple active site) non-ribosomal peptide synthases. Each active site catalyses a step in which amino acids are combined to create a peptide without RNA
Matzanke et al 2004 FhuF gene product was isolated from E.Coli and shown to reduce iron to Fe2+ in vitro although knockout bacteria were not growth impaired implying at least one other route to Fe reduction. This enzyme is thought to mediate fe release from the siderophore.
Searle et al 1998 Shows localisation of Nramp1 iron transporter to endosomes and lysosomes of infected macrophages. Thought to extrude iron from these compartments to inhibit bacterial function
Lamont et al 2002 Positive feedback of returning siderophores, placed beta galactosidase (lacz) under pyoverdine promoter, mutant p.aeru lacking pyoverdine had reduced expression of lacz. Fpvr receptor binds pyoverdine and releases Pvds which activates gene expression.
Tiburzi et al 2007 Questions whether non-ribosomal peptide synthetases occur in higher eukaryotes. We still havent found any but would be odd if they werent. Peptides made this way can contain unusual amino acids
Braun & Hantke 2011 Review: Fe3+ is insoluble and toxic due to free radicals. We complex free serum haemoglobin with haptoglobin for excretion by the liver. Similarly hemopexin sequesters free haem. Bacteria may use a new transporter in low iron to collect more aggressively
Created by: Jonmassie



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