Metals: Ironing out copper toxicity (original) (raw)
Related papers
Journal of The American Chemical Society, 2008
The siderophore enterobactin (Ent) is produced by enteric bacteria to mediate iron uptake. Ent scavenges iron and is taken up by the bacteria as the highly stable ferric complex [Fe III (Ent)] 3-. This complex is also a specific target of the mammalian innate immune system protein, Siderocalin (Scn), which acts as an anti-bacterial agent by specifically sequestering siderophores and their ferric complexes during infection. Recent literature suggesting that Scn may also be involved in cellular iron transport has increased the importance of understanding the mechanism of siderophore interception and clearance by Scn; Scn is observed to release iron in acidic endosomes and [Fe III (Ent)] 3is known to undergo a change from catecholate to salicylate coordination in acidic conditions, which is predicted to be sterically incompatible with the Scn binding pocket (also referred to as the calyx). To investigate the interactions between the ferric Ent complex and Scn at different pH values, two recombinant forms of Scn with mutations in three residues lining the calyx were prepared: Scn-W79A/R81A and Scn-Y106F. Binding studies and crystal structures of the Scn-W79A/R81A:[Fe III (Ent)] 3and Scn-Y106F:[Fe III (Ent)] 3complexes confirm that such mutations do not affect the overall conformation of the protein but do weaken significantly its affinity for [Fe III (Ent)] 3-. Fluorescence, UV-Vis and EXAFS spectroscopies were used to determine Scn/siderophore dissociation constants and to characterize the coordination mode of iron over a wide pH range, in the presence of both mutant proteins and synthetic salicylate analogs of Ent. While Scn binding hinders salicylate coordination transformation, strong acidification results in the release of iron and degraded siderophore. Iron release may therefore result from a combination of Ent degradation and coordination change.
Current microbiology, 2006
The majority of bacteria isolated from rhizospheres of Arachis hypogea (Groundnut) and Vigna radiata (Mung bean) predominantly produced catechol-type siderophores except for a few fluorescent pseudomonads that produced hydroxamates in addition to catecholates. The rhizospheric isolates differed in their ability to cross-utilize siderophores produced by other rhizospheric isolates (heterologous); some were highly proficient at utilizing heterologous siderophores, while others were poor cross-utilizers. Isolate G9, which utilized hydroxamate as well as catecholate siderophores, was found to be an efficient siderophore cross-utilizer, while isolates G2 and G6 were poor-utilizers of catecholate and non-utilizers of hydroxamate siderophores. Growth stimulation of two isolates G9 and G6 was seen when grown in the presence of externally supplied heterologous siderophores, which they cross-utilized. The iron-regulated outer membrane protein (IROMP) profiles differed for the most crossutilizer and the least cross-utilizer strains, but in both the cases no new outer membrane proteins (OMP) were induced in response to the exogenous siderophores supplied. The growth of the organisms in the presence of heterologous siderophores that they failed to cross-utilize led to growth inhibition in the case of isolate G9. This appears to be due to a lower affinity of the siderophore of G9 as compared to the exogenously supplied G6 siderophore. A simple method was devised to measure relative affinities of respective siderophores for iron based on CAS solution decolorization by the siderophore preparations. The effect on the growth of the differential affinities of the siderophores for iron and the interactions of the organisms through cross-utilization is also discussed.
The importance of siderophores in iron nutrition of heterotrophic marine bacteria
Limnology and Oceanography, 1999
Recent studies demonstrate that dissolved iron in seawater is bound to strong organic complexes that have stability constants comparable to those of microbial iron chelates. We examined iron acquisition by seven strains of heterotrophic marine bacteria from a number of siderophore-iron complexes, including desferrioxamine B (DFB) and marine siderophores partially purified from iron-limited cultures. Hydroxamate siderophores were detected in the supernatants of four strains, one of which also produced a catechol. All strains transported iron bound to siderophores regardless of whether or not they produced their own, and the majority took up iron bound to DFB. Uptake rates of Fe siderophores were similar among iron-limited strains and among ligands. Transport of FeDFB by strain Neptune was enhanced 20 times by iron limitation, whereas uptake of unchelated iron (FeЈ) did not saturate at the highest concentration tested and was not regulated by the iron nutritional status of the cells. The half-saturation constant for uptake of FeDFB by Neptune was 15 nM, the lowest reported for an Fe siderophore in any microorganism. Iron uptake by the catechol-producing strain, LMG1, differed markedly in two respects from the other strains: LMG1 could not take up iron bound to DFB; furthermore, transport of FeЈ by iron-limited LMG1 was 10 times faster than the other strains and was upregulated 46 times compared to Fe-sufficient cells. Experimental evidence suggests that iron transport by LMG1 may be mediated by surface-associated catechol siderophores that scavenge inorganic ferric species as well as iron bound to weaker complexes, such as EDTA (ethylenediaminetetraacetic acid). The combined results of the study highlight the importance of siderophores in iron transport by heterotrophic marine bacteria and suggest, by inference, that bacteria may rely on siderophores to acquire iron in situ.
Archives of Microbiology, 2023
Iron is one of the highly abundant elements on the earth's crust, an essential micronutrient for a majority of life forms, and exists in two frequent oxidation states such as ferrous (Fe 2+) and ferric (Fe 3+). These two oxidation states are interconvertible by redox reactions and form complexes with a wide range of siderophores. At neutral pH in soil, Fe 2+ is highly soluble upto 100 mM but have less biological value, whereas Fe 3+ is less soluble upto 10-9 M. This reduced bioavailability of Fe 3+ induces competition among microorganisms. As many microorganisms need at least 10-6 M of Fe 3+ form of iron for their growth, siderophores from these microbes readily withdraw Fe 3+ iron from a variety of habitats for their survival. In this review, we bring into light the several recent investigations related to diverse chemistry of microbial siderophores, mechanisms of siderophore uptake, biosynthetic gene clusters in microbial genomes, various sources of heavy metal cations in soil, siderophore-binding protein receptors and commercialisation perspectives of siderophores. Besides, this review unearths the recent advancements in the characterisation of novel siderophores and its heavy metal complexes alongside the interaction kinetics with receptors.
More than 60% of species examined from a total of 421 strains of heterotrophic marine bacteria which were isolated from marine sponges and seawater were observed to have no detectable siderophore production even when Fe(III) was present in the culture medium at a concentration of 1.0 pM. The growth of one such non-siderophore-producing strain, alpha proteobacterium V0210, was stimulated under iron-limited conditions with the addition of an isolated exogenous siderophore, N,N-bis (2,3-dihydroxybenzoyl)-O-serylserine from a Vibrio sp. Growth was also stimulated by the addition of three exogenous siderophore extracts from siderophore-producing bacteria. Radioisotope studies using 59 Fe showed that the iron uptake ability of V0210 increased only with the addition of exogenous siderophores. Biosynthesis of a hydroxamate siderophore by V0210 was shown by paper electrophoresis and chemical assays for the detection of hydroxamates and catechols. An 85-kDa iron-regulated outer membrane protein was induced only under iron-limited conditions in the presence of exogenous siderophores. This is the first report of bacterial iron uptake through an induced siderophore in response to exogenous siderophores. Our results suggest that siderophores are necessary signaling compounds for growth and for iron uptake by some non-siderophore-producing marine bacteria under iron-limited conditions.
Proteobactin and a yersiniabactin-related siderophore mediate iron acquisition in Proteus mirabilis
Molecular Microbiology, 2010
Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an ironlimiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes (P Յ 0.05) that represent 21 putative iron-regulated systems. Two gene clusters, PMI0229-0239 and PMI2596-2605, encode putative siderophore systems. PMI0229-0239 encodes a non-ribosomal peptide synthetase-independent siderophore system for producing a novel siderophore, proteobactin. PMI2596-2605 are contained within the high-pathogenicity island, originally described in Yersinia pestis, and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross-feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin-related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron-chelating defect; demonstrating production and iron-chelating activity for both siderophores. These findings clearly show that proteobactin and the yersiniabactin-related siderophore function as iron acquisition systems. Despite the activity of both siderophores, only mutants lacking the yersiniabactinrelated siderophore have reduced fitness in vivo. The fitness requirement for the yersiniabactin-related siderophore during UTI shows, for the first time, the importance of siderophore production in vivo for P. mirabilis.