The Purified Siderophore from Streptomyces tricolor HM10 Accelerates Recovery from Iron-Deficiency-Induced Anemia in Rats

Abstract

Iron-deficiency-induced anemia is associated with poor neurological development, including decreased learning ability, altered motor functions, and numerous pathologies. Siderophores are iron chelators with low molecular weight secreted by microorganisms. The proposed catechol-type pathway was identified based on whole-genome sequences and bioinformatics tools. The intended pathway consists of five genes involved in the biosynthesis process. Therefore, the isolated catechol-type siderophore (Sid) from Streptomyces tricolor HM10 was evaluated through an anemia-induced rat model to study its potential to accelerate recovery from anemia. Rats were subjected to an iron-deficient diet (IDD) for 42 days. Anemic rats (ARs) were then divided into six groups, and normal rats (NRs) fed a standard diet (SD) were used as a positive control group. For the recovery experiment, ARs were treated as a group I; fed an IDD (AR), group II; fed an SD (AR + SD), group III, and IV, fed an SD with an intraperitoneal injection of 1 μg Sid Kg−1 (AR + SD + Sid1) and 5 μg Sid Kg−1 (AR + SD + Sid5) twice per week. Group V and VI were fed an iron-enriched diet (IED) with an intraperitoneal injection of 1 μg Sid Kg−1 (AR + IED + Sid1) and 5 μg Sid Kg−1 (AR + IED + Sid5) twice per week, respectively. Weight gain, food intake, food efficiency ratio, organ weight, liver iron concentration (LIC) and plasma (PIC), and hematological parameters were investigated. The results showed that ~50–60 mg Sid L−1 medium could be producible, providing ~25–30 mg L−1 purified Sid under optimal conditions. Remarkably, the AR group fed an SD with 5 μg Sid Kg−1 showed the highest weight gain. The highest feed efficiency was observed in the AR + SD + Sid5 group, which did not significantly differ from the SD group. Liver, kidneys, and spleen weight indicated that diet and Sid concentration were related to weight recovery in a dose-dependent manner. Liver iron concentration (LIC) in the AR + IED + Sid1 and AR + IED + Sid5 groups was considerably higher than in the AR + SD + Sid1 AR + SD + Sid5 groups or the AR + SD group compared to the AR group. All hematological parameters in the treated groups were significantly closely attenuated to SD groups after 28 days, confirming the efficiency of the anemia recovery treatments. Significant increases were obtained in the AR + SD + Sid5 and AR + IED + Sid5 groups on day 14 and day 28 compared to the values for the AR + SD + Sid1 and AR + IED + Sid1 groups. The transferrin saturation % (TSAT) and ferritin concentration (FC) were significantly increased with time progression in the treated groups associatively with PIC. In comparison, the highest significant increases were noticed in ARs fed IEDs with 5 μg Kg−1 Sid on days 14 and 28. In conclusion, this study indicated that Sid derived from S. tricolor HM10 could be a practical and feasible iron-nutritive fortifier when treating iron-deficiency-induced anemia (IDA). Further investigation focusing on its mechanism and kinetics is needed.

Optimization of Siderophore Production in Three Marine Bacterial Isolates along with Their Heavy-Metal Chelation and Seed Germination Potential Determination

“…Under Fe +3 -deficient growth conditions, the hydrophobicity of the microbial surface is greatly decreased, leading to changes in the composition of surface proteins followed by limitation of biofilm formation, which then ultimately results in microbial death [16]. Therefore, during the low bioavailability of Fe +3 in the surrounding habitat, siderophores are produced and secreted by the microbes; to date, it is one of the evolutionary coping mechanisms developed by microbes to survive in a Fe-deficient habitat [16]. With the help of siderophores, microbes can uptake Fe in the form of Fe +3 -siderophore complexes, and then, in the cytosol, Fe is reduced and released as Fe +2 [3].…”

“…Depending on membrane affinity and length, siderophores could anchor a particular gradient outside the microbial membrane, thereby increasing the efficiency of siderophores in chelating Fe +3 from the environment [16]. On the other hand, Fe +3 acquisition is closely regulated by the microbes, as the occurrence of intracellular Fe +3 in excess amounts will result in oxidative stress, leading to microbial death.…”

“…In this regard, siderophores also act as key regulators in microbial Fe homeostasis [8]. In comparison with other metal ions, Fe +3 is preferentially chelated by siderophores [16,18]. Siderophores can be further classified into carboxylates, catecholates, hydroxamates, and mixed-types siderophores depending on the primary oxygen-donating ligands, which bind with Fe +3 [2].…”

Special Issue—“Isolation, Structure Elucidation and Biological Activity of Natural Products”

“…Bacteria and fungi are also important producers of bioactive metabolites. The purification of a catechol-type siderophore from Streptomyces tricolor was studied with the aim of inducing recovery from iron-deficiency-induced anemia in in vivo rat model (Barakat et al, 2022) [ 11 ]. Siderophores are low-molecular-weight natural compounds secreted by microorganisms that act as iron chelators.…”

“…Iron chelators are also useful in cancer therapy because cancer cells have higher requirements of iron when compared to healthy cells. Barakat et al (2022) focused on applications related to the damages caused by iron-deficiency-induced anemia, showing that sidereophores improved weight gain and were effective during recovery from anemia [ 11 ]. The results led the authors to propose some hypotheses and created opportunities to delineate the detailed mechanism of the changes observed and elucidate iron pathways.…”