Siderophores are a class of small molecules renowned for their high iron binding capacity, essential for all life forms requiring iron. This article provides a detailed review of the diverse classifications, and biosynthetic pathways of siderophores, with a particular emphasis on siderophores synthesized via nonribosomal peptide synthetase (NRPS) and non-NRPS pathways. We further explore the secretion mechanisms of siderophores in microbes and plants, and their role in regulating bioavailable iron levels. Beyond biological functions, the applications of siderophores in medicine, agriculture, and environmental sciences are extensively discussed. These applications include biological pest control, disease treatment, ecological pollution remediation, and heavy metal ion removal. Through a comprehensive analysis of the chemical properties and biological activities of siderophores, this paper demonstrates their wide prospects in scientific research and practical applications, while also highlighting current research gaps and potential future directions.

Synthetic fertilizers and pesticides are being extensively used in agriculture in order to increase food production to feed the rapidly growing world population. This has negatively affected the soil microbes thereby reducing the agricultural produce. As a safer alternative, microbial fertilizers are now being used as plant growth promoters to improve agricultural yields. A large number of studies are focused on the role of bacteria and multicellular fungi, but plant growth-promoting traits of yeasts, the unicellular fungi are little known. Hence, the present article reviewed the diverse groups of yeasts with the potential to act as plant growth promoters. Plant growth-promoting yeasts (PGPY) have been mainly isolated from the rhizosphere and phyllosphere of major crop plants such as wheat, maize, and rice. Twenty-three genera of yeasts have been reported to have the potential for plant growth promotion (PGP), most of which belong to the phylum Ascomycetes. Dominant PGPY genera include Candida spp., Rhodotorula spp., Cryptococcus spp., and Saccharomyces sp. PGPY are known to exhibit phyto-beneficial attributes viz phytohormone production, phosphate solubilization, siderophore production, improved soil fertility, aid plants to tolerate abiotic stress and also compete effectively against plant pathogens. Over and above these traits, PGPY is Generally Recognized as Safe, making it an ideal candidate to be effectively employed as part of sustainable agricultural practices to ensure food security. The review warrants a need for an in-depth study on the different sources of PGPY other than rhizosphere/phyllosphere and the genes controlling PGP traits.

The ubiquitous bacterium Staphylococcus aureus causes many diseases that sometimes can be fatal due to its high pathogenicity. The latter is caused by the ability of this pathogen to secrete secondary metabolites, enabling it to colonize inside the host causing infection through various processes. Metallophores are secondary metabolites that enable bacteria to sequester metal ions from the surrounding environment since the availability of metal ions is crucial for bacterial metabolism and virulence. The uptake of iron and other metal ions such as nickel and zinc is one of these essential mechanisms that gives this germ its virulence properties and allow it to overcome the host immune system. Additionally, extensive interactions occur between this pathogen and other bacteria as they compete for resources. Staphylococcus aureus has high-affinity metal import pathways including metal ions acquisition, recruitment and metal-chelate complex import. These characteristics give this bacterium the ability to intake metallophores synthesized by other bacteria, thus enabling it to compete with other microorganisms for the limited nutrients. In scarce host conditions, free metal ions are extremely low because they are confined to storage and metabolic molecules, so metal ions are sequestered by metallophores produced by this bacterium. Both siderophores (iron chelating molecules) and staphylopine (wide- spectrum metallophore) are secreted by Staphylococcus aureus giving it infectious properties. The genetic regulation of the synthesis and export together with the import of metal loaded metallophores are well established and are all covered in this review.

Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is responsible for the production of sweat, digestive fluids, and mucus, and any mutation in this would lead to the thickening of these secretions. Cystic fibrosis is a multi-organ disorder, but 80% of patients suffer from respiratory problems due to chronic infections most commonly caused by Pseudomonas aeruginosa (P. aeruginosa). Eradication of these infections has become a challenge as P. aeruginosa has developed resistance to multiple antibiotics. In several studies, iron has been shown to play an integral role in biofilm formation, which is the predominant resistance mechanism used by P. aeruginosa to combat antibiotics. The increased iron content in cystic fibrosis patients\' sputum samples explains their increased susceptibility to Pseudomonas infections. Hence in this review article, we have used the research data available on therapeutic agents that target iron as an adjuvant treatment for chronic Pseudomonas infection. We systematically screened three databases using focused words and Medical Subject Headings (MeSH) terms for relevant articles. Further, we applied the inclusion and exclusion criteria and performed a thorough quality appraisal. Thirty shortlisted relevant studies were meticulously reviewed. In our opinion, novel therapeutic approaches targeting iron such as iron chelators, gallium, and cefiderocol have potent anti-biofilm properties. Future studies and clinical trials using these approaches in the management of chronic Pseudomonas infection might help in decreasing morbidity and mortality in patients with cystic fibrosis. Exploring these approaches might also help to combat other resistant organisms whose survival is dependent on iron.

Dyshomeostasis of trace elements have been implicated in the progression of Alzheimer\'s disease (AD), which is characterized by amyloid-β (Aβ) plaques. Trace elements are particularly associated with the Aβ plaques. Metal-protein attenuating compounds have been developed to inhibit metals from binding to Aβ proteins, which result in Aβ termination, in the hope of improving cognitive functioning. However, there are still some contradicting reports. This review aims to first establish which trace elements are increased or decreased in the brains of Alzheimer\'s patients, and secondly, to review the effectiveness of clinical trials with metal-protein attenuating compounds for AD. Studies have consistently reported unchanged or increased iron, contradicting reports for zinc, decreased copper, unchanged or decreased manganese, inconsistent results for calcium, and magnesium seems to be unaffected. However, varied results have been reported for all trace elements. Clinical trials using metal-protein attenuating compounds to treat AD have also reported varied results. Copper chelators have repeatedly been used in clinical trials, even though few studies report increased brain copper levels in AD patients. Homeostasis of copper levels is important since copper has a vital role in several enzymes, such as cytochrome c, Cu/Zn superoxide dismutase and ceruloplasmin. Dyshomeostasis of copper levels can lead to increased oxidative stress and neuronal loss. Future studies should assess a variety of trace element levels in moderately and severely affected AD patients since there are contradicting reports. This review thus provides some insight into trace element alterations in the brains of individuals with AD.

Asbestos, silicate minerals present in soil and used for building constructions for many years, are highly toxic due primarily to the presence of high concentrations of the transition metal iron. Microbial weathering of asbestos occurs through various alteration mechanisms. Siderophores, complex agents specialized in metal chelation, are common mechanisms described in mineral alteration. Solubilized metals from the fiber can serve as micronutrients for telluric microorganisms. The review focuses on the bioweathering of asbestos fibers, found in soil or manufactured by humans with gypsum (asbestos flocking) or cement, by siderophore-producing Pseudomonas. A better understanding of the interactions between asbestos and bacteria will give a perspective of a detoxification process inhibiting asbestos toxicity.

New eco-friendly approaches are required to improve plant biomass production. Beneficial plant growth-promoting (PGP) bacteria may be exploited as excellent and efficient biotechnological tools to improve plant growth in various - including stressful - environments. We present an overview of bacterial mechanisms which contribute to plant health, growth, and development. Plant growth promoting rhizobacteria (PGPR) can interact with plants directly by increasing the availability of essential nutrients (e.g. nitrogen, phosphorus, iron), production and regulation of compounds involved in plant growth (e.g. phytohormones), and stress hormonal status (e.g. ethylene levels by ACC-deaminase). They can also indirectly affect plants by protecting them against diseases via competition with pathogens for highly limited nutrients, biocontrol of pathogens through production of aseptic-activity compounds, synthesis of fungal cell wall lysing enzymes, and induction of systemic responses in host plants. The potential of PGPR to facilitate plant growth is of fundamental importance, especially in case of abiotic stress, where bacteria can support plant fitness, stress tolerance, and/or even assist in remediation of pollutants. Providing additional evidence and better understanding of bacterial traits underlying plant growth-promotion can inspire and stir up the development of innovative solutions exploiting PGPR in times of highly variable environmental and climatological conditions.

Pseudomonas aeruginosa is one of the most prominent opportunistic bacteria in airways of cystic fibrosis patients and in immunocompromised patients. These bacteria share the same polymicrobial niche with other microbes, such as the opportunistic fungus Aspergillus fumigatus. Their inter-kingdom interactions and diverse exchange of secreted metabolites are responsible for how they both fare in competition for ecological niches. The outcomes of their contests likely determine persistent damage and degeneration of lung function. With a myriad of virulence factors and metabolites of promising antifungal activity, P. aeruginosa products or their derivatives may prove useful in prophylaxis and therapy against A. fumigatus. Quorum sensing underlies the primary virulence strategy of P. aeruginosa, which serves as cell-cell communication and ultimately leads to the production of multiple virulence factors. Understanding the quorum-sensing-related pathogenic mechanisms of P. aeruginosa is a first step for understanding intermicrobial competition. In this review, we provide a basic overview of some of the central virulence factors of P. aeruginosa that are regulated by quorum-sensing response pathways and briefly discuss the hitherto known antifungal properties of these virulence factors. This review also addresses the role of the bacterial secretion machinery regarding virulence factor secretion and maintenance of cell-cell communication.

The bacterial infection is one of the major health issues throughout the world. To protect humans from the infection and infectious agents, it is important to understand the mechanism of interaction of pathogens along with their susceptible hosts. This will help us to develop a novel strategy for designing effective new drugs or vaccines. As iron is an essential metal ion required for all the living systems for their growth, as well, it is needed by pathogenic bacterial cells for their growth and development inside host tissues. To get iron from the host tissues, microbes developed an iron-chelating system called siderophore and also corresponding receptors. Siderophores are low molecular weight organic complex produced by different strains of bacteria for the procurement of iron from the environment or host body under the iron deficient-conditions. Mostly in the environment at physiological pH, the iron is present in the ferric ionic form (Fe3+), which is water- insoluble and thus inaccessible for them. Such a condition promotes the generation of siderophores. These siderophores have been used in different areas such as agriculture, treatment of diseases, culture the unculturable strains of bacteria, promotion of plant growth, controlling phytopathogens, detoxification of heavy metal contamination, etc. In the medical field, siderophores can be used as \"Trojan Horse Strategy\", which forms a complex with antibiotics and also delivers these antibiotics to the desired locations, especially in antibiotic-resistant bacteria. The promising application of siderophore-based use of antibiotics for the management of bacterial resistance can be strategies to be used.

The rapid increase in world population has generated the issues of hunger, poverty, food insecurity and malnutrition. To meet the challenge of increased food production of better quality, the farmers were compelled to use more chemical fertilizers, especially in developing countries. The higher use of chemical fertilizers interrupts the food chain through eutrophication, the polluting air and soil by incorporating metals. Trace metals have a deleterious effect on soil microbial and plant growth. To minimize metal toxicity and maximize the production of food, there are different approaches that can lead to lessen the use of chemical fertilizers. Plant growth promoting rhizobacteria (PGPR) are capable to enhance the plant growth and can remediate metal contaminated soils. PGPR has the ability to improve food production with diverse attributes e.g. producing siderophores that promote rhizosphere trace metal sequestration and production of organic and inorganic acids thus affecting trace metal bioavailability and plant induced systemic tolerance (IST) to limit the crop metal accumulation. In this review paper, we have discussed the biological approach which is environmentally friendly and cost-effective mean for metal polluted soils and gives some new insights for safety use of PGPR in trace metal contaminated fields.