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Background: Infection remains a major cause of morbidity and mortality, regardless of advances in antimicrobial therapy and improved knowledge of microorganisms. With the major global threat posed by antimicrobial resistance, fast and accurate diagnosis of infections, and the reliable identification of intractable infection, are becoming more crucial for effective treatment and the application of antibiotic stewardship. Molecular imaging with the use of nuclear medicine allows early detection and localisation of infection and inflammatory processes, as well as accurate monitoring of treatment response. There has been a continuous search for more specific radiopharmaceuticals to be utilised for infection imaging. This review summarises the most prominent discoveries in specifically bacterial infection imaging agents over the last five years, since 2019. Main body: Some promising new radiopharmaceuticals evaluated in patient studies are reported here, including radiolabelled bacterial siderophores like [68Ga]Ga-DFO-B, radiolabelled antimicrobial peptide/peptide fragments like [68Ga]Ga-NOTA-UBI29-41, and agents that target bacterial synthesis pathways (folic acid and peptidoglycan) like [11C]para-aminobenzoic acid and D-methyl-[11C]-methionine, with clinical trials underway for [18F]fluorodeoxy-sorbitol, as well as for 11C- and 18F-labelled trimethoprim. Conclusion: It is evident that a great deal of effort has gone into the development of new radiopharmaceuticals for infection imaging over the last few years, with remarkable progress in preclinical investigations. However, translation to clinical trials, and eventually clinical Nuclear Medicine practice, is apparently slow. It is the authors' opinion that a more structured and harmonised preclinical setting and well-designed clinical investigations are the key to reliably evaluate the true potential of the newly proposed infection imaging agents. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract is densely colonized by a polymicrobial community known as the microbiota which serves as primary line of defence against pathogen invasion. The microbiota can limit gut-luminal pathogen growth at different stages of infection. This can be traced to specific commensal strains exhibiting direct or indirect protective functions. Although these mechanisms hold the potential to develop new approaches to combat enteric pathogens, they remain far from being completely described. In this study, we investigated how a mouse commensal Escherichia coli can outcompete Salmonella enterica serovar Typhimurium (S. Tm). Using a salmonellosis mouse model, we found that the commensal E. coli 8178 strain relies on a trojan horse trap strategy to limit S. Tm expansion in the inflamed gut. Combining mutants and reporter tools, we demonstrated that inflammation triggers the expression of the E. coli 8178 antimicrobial microcin H47 toxin which, when fused to salmochelin siderophores, can specifically alter S. Tm growth. This protective function was compromised upon disruption of the E. coli 8178 tonB-dependent catecholate siderophore uptake system, highlighting a previously unappreciated crosstalk between iron intake and microcin H47 activity. By identifying the genetic determinants mediating S. Tm competition, our work not only provides a better mechanistic understanding of the protective function displayed by members of the gut microbiota but also further expands the general contribution of microcins in bacterial antagonistic relationships. Ultimately, such insights can open new avenues for developing microbiota-based approaches to better control intestinal infections. The microbiota serves as the first line of defence against pathogen invasion in the gut. This study shows that, in a mouse model of salmonellosis, commensal E. coli 8178 uses a trojan horse strategy to limit the expansion of Salmonella in the inflamed gut, using microcin H47 fused to salmochelin siderophores. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Covering: 2005 to August, 2023 Polyamine-containing natural products (NPs) have been isolated from a wide range of terrestrial and marine organisms and most of them exhibit remarkable and diverse activities, including antimicrobial, antiprotozoal, antiangiogenic, antitumor, antiviral, iron-chelating, anti-depressive, anti-inflammatory, insecticidal, antiobesity, and antioxidant properties. Their extraordinary activities and potential applications in human health and agriculture attract increasing numbers of studies on polyamine-containing NPs. In this review, we summarized the source, structure, classification, bioactivities and biosynthesis of polyamine-containing NPs, focusing on the biosynthetic mechanism of polyamine itself and representative polyamine alkaloids, polyamine-containing siderophores with catechol/hydroxamate/hydroxycarboxylate groups, nonribosomal peptide-(polyketide)-polyamine (NRP-(PK)-PA), and NRP-PK-long chain poly-fatty amine (lcPFAN) hybrid molecules. [ABSTRACT FROM AUTHOR]

Many countries banned asbestos due to its toxicity, but considering its colossal use, especially in the 1960s and 1970s, disposing of waste containing asbestos is the current problem. Today, many asbestos disposal technologies are known, but they usually involve colossal investment and operating expenses, and the end- and by-products of these methods negatively impact the environment. This paper identifies a unique modern direction in detoxifying asbestos minerals, which involves using microorganisms and plants and their metabolites. The work comprehensively focuses on the interactions between asbestos and plants, bacteria and fungi, including lichens and, for the first time, yeast. Biological treatment is a prospect for in situ land reclamation and under industrial conditions, which can be a viable alternative to landfilling and an environmentally friendly substitute or supplement to thermal, mechanical, and chemical methods, often characterized by high cost intensity. Plant and microbial metabolism products are part of the green chemistry trend, a central strategic pillar of global industrial and environmental development. [ABSTRACT FROM AUTHOR]

The emergence of multidrug-resistant (MDR) microorganisms combined with the ever-draining antibiotic pipeline poses a disturbing and immensely growing public health challenge that requires a multidisciplinary approach and the application of novel therapies aimed at unconventional targets and/or applying innovative drug formulations. Hence, bacterial iron acquisition systems and bacterial Fe2+/3+-containing enzymes have been identified as a plausible target of great potential. The intriguing "Trojan horse" approach deprives microorganisms from the essential iron. Recently, gallium's potential in medicine as an iron mimicry species has attracted vast attention. Different Ga3+ formulations exhibit diverse effects upon entering the cell and thus supposedly have multiple targets. The aim of the current study is to specifically distinguish characteristics of great significance in regard to the initial gallium-based complex, allowing the alien cation to effectively compete with the native ferric ion for binding the siderophores pyochelin and pyoverdine secreted by the bacterium P. aeruginosa. Therefore, three gallium-based formulations were taken into consideration: the first-generation gallium nitrate, Ga(NO3)3, metabolized to Ga3+-hydrated forms, the second-generation gallium maltolate (tris(3-hydroxy-2-methyl-4-pyronato)gallium), and the experimentally proven Ga carrier in the bloodstream—the protein transferrin. We employed a reliable in silico approach based on DFT computations in order to understand the underlying biochemical processes that govern the Ga3+/Fe3+ rivalry for binding the two bacterial siderophores. [ABSTRACT FROM AUTHOR]

A fully enantioselective, catalytic synthesis of the algal morphogen (−)‐thallusin using polyene cyclization chemistry is reported. The synthesis features dedicated precursor design, introduction of a TMS‐substituted arene as a regioselective terminator, very high enantiomer excess (ee) on gram scale, and productive scaffold functionalization. Furthermore, an ee determination methodology of thallusin samples was developed, and the ee of biosynthesized thallusin was determined. Fe(III)‐uptake studies demonstrated that the cellular uptake of iron facilitated by thallusin derivatives was independent of their morphogenic activity, suggesting their active import via siderophore transporters as a shuttle system. [ABSTRACT FROM AUTHOR]

Background: The emergence of antimicrobial resistance in bacterial pathogens is a growing concern worldwide due to its impact on the treatment of bacterial infections. The "Trojan Horse" strategy has been proposed as a potential solution to overcome drug resistance caused by permeability issues. Objective: The objective of our research was to investigate the bactericidal activity and mechanism of action of the "Trojan Horse" strategy using enterobactin conjugated with Ciprofloxacin and Fosfomycin against the antibiotic-resistant Escherichia coli strain OQ866153. Methodology: Enterobactin, a mixed ligand of E. coli OQ866153, was conjugated with Ciprofloxacin and Fosfomycin individually to aid active absorption via specific enterobactin binding proteins (FepABCDG). The effectiveness of the conjugates was assessed by measuring their bactericidal activity against E. coli OQ866153, as well as their ability to inhibit DNA gyrase enzyme and biofilm formation. Results: The Fe+3-enterobactin-Ciprofloxacin conjugate effectively inhibited the DNA gyrase enzyme (Docking score = -8.597 kcal/mol) and resulted in a lower concentration (25 μg/ml) required to eliminate supercoiled DNA plasmids compared to the parent drug (35 μg/ml; Docking score = -6.264 kcal/mol). The Fe+3-Enterobactin-Fosfomycin conjugate showed a higher inhibition percentage (100%) of biofilm formation compared to Fosfomycin (21.58%) at a concentration of 2 mg/ml, with docking scores of -5.481 and -3.756 kcal/mol against UDP-N acetylglucosamine 1-carboxyvinyltransferase MurA. Conclusion: The findings of this study suggest that the "Trojan Horse" strategy using enterobactin conjugated with Ciprofloxacin and Fosfomycin can effectively overcome permeability issues caused by efflux proteins and enhance the bactericidal activity of these drugs against antibiotic-resistant strains of E. coli. [ABSTRACT FROM AUTHOR]

Actinobacteria are one of the predominant groups that successfully colonize and survive in various aquatic, terrestrial and rhizhospheric ecosystems. Among actinobacteria, Nocardia is one of the most important agricultural and industrial bacteria. Screening and isolation of Nocardia related bacteria from extreme habitats such as endolithic environments are beneficial for practical applications in agricultural and environmental biotechnology. In this work, bioinformatics analysis revealed that a novel strain Nocardia mangyaensis NH1 has the capacity to produce structurally varied bioactive compounds, which encoded by non-ribosomal peptide synthases (NRPS), polyketide synthase (PKS), and post-translationally modified peptides (RiPPs). Among NRPS, five gene clusters have a sequence homology with clusters encoding for siderophore synthesis. We also show that N. mangyaensis NH1 accumulates both catechol- and hydroxamate-type siderophores simultaneously under iron-deficient conditions. Untargeted LC–MS/MS analysis revealed a variety of metabolites, including siderophores, lipopeptides, cyclic peptides, and indole-3-acetic acid (IAA) in the culture medium of N. mangyaensis NH1 grown under iron deficiency. We demonstrate that four CAS (chrome azurol S)-positive fractions display variable affinity to metals, with a high Fe3+ chelating capability. Additionally, three of these fractions exhibit antioxidant activity. A combination of iron scavenging metabolites produced by N. mangyaensis NH1 showed antifungal activity against several plant pathogenic fungi. We have shown that the pure culture of N. mangyaensis NH1 and its metabolites have no adverse impact on Arabidopsis seedlings. The ability of N. mangyaensis NH1 to produce siderophores with antifungal, metal-chelating, and antioxidant properties, when supplemented with phytohormones, has the potential to improve the release of macro- and micronutrients, increase soil fertility, promote plant growth and development, and enable the production of biofertilizers across diverse soil systems. [ABSTRACT FROM AUTHOR]

Background: Siderophores are small iron-binding molecules produced by microorganisms to facilitate iron acquisition from the environment. Radiolabelled siderophores offer a promising solution for infection imaging, as they can specifically target the pathophysiological mechanisms of pathogens. Gallium-68 can replace the iron in siderophores, enabling molecular imaging with positron emission tomography (PET). Stereospecific interactions play a crucial role in the recognition of receptors, transporters, and iron utilisation. Furthermore, these interactions have an impact on the host environment, affecting pharmacokinetics and biodistribution. This study examines the influence of siderophore stereoisomerism on imaging properties, with a focus on ferrirubin (FR) and ferrirhodin (FRH), two cis–trans isomeric siderophores of the ferrichrome type. Results: Tested siderophores were labelled with gallium-68 with high radiochemical purity. The resulting complexes differed in their in vitro characteristics. [68Ga]Ga-FRH showed less hydrophilic properties and higher protein binding values than [68Ga]Ga-FR. The stability studies confirmed the high radiochemical stability of both [68Ga]Ga-siderophores in all examined media. Both siderophores were found to be taken up by S. aureus, K. pneumoniae and P. aeruginosa with similar efficacy. The biodistribution tested in normal mice showed rapid renal clearance with low blood pool retention and fast clearance from examined organs for [68Ga]Ga-FR, whereas [68Ga]Ga-FRH showed moderate retention in blood, resulting in slower pharmacokinetics. PET/CT imaging of mice injected with [68Ga]Ga-FR and [68Ga]Ga-FRH confirmed findings from ex vivo biodistribution studies. In a mouse model of S. aureus myositis, both radiolabeled siderophores showed radiotracer accumulation at the site of infection. Conclusions: The 68Ga-complexes of stereoisomers ferrirubin and ferrirhodin revealed different pharmacokinetic profiles. In vitro uptake was not affected by isomerism. Both compounds had uptake with the same bacterial culture with similar efficacy. PET/CT imaging showed that the [68Ga]Ga-complexes accumulate at the site of S. aureus infection, highlighting the potential of [68Ga]Ga-FR as a promising tool for infection imaging. In contrast, retention of the radioactivity in the blood was observed for [68Ga]Ga-FRH. In conclusion, the stereoisomerism of potential radiotracers should be considered, as even minor structural differences can influence their pharmacokinetics and, consequently, the results of PET imaging. [ABSTRACT FROM AUTHOR]

Iron is essential to many biological processes but its poor solubility in aerobic environments restricts its bioavailability. To overcome this limitation, bacteria have evolved a variety of strategies, including the production and secretion of iron-chelating siderophores. Here, we describe the discovery of four series of siderophores from Streptomyces ambofaciens ATCC23877, three of which are unprecedented. MS/MS-based molecular networking revealed that one of these series corresponds to acylated desferrioxamines (acyl-DFOs) recently identified from S. coelicolor. The remaining sets include tetra- and penta-hydroxamate acyl-DFO derivatives, all of which incorporate a previously undescribed building block. Stable isotope labeling and gene deletion experiments provide evidence that biosynthesis of the acyl-DFO congeners requires unprecedented crosstalk between two separate non-ribosomal peptide synthetase (NRPS)-independent siderophore (NIS) pathways in the producing organism. Although the biological role(s) of these new derivatives remain to be elucidated, they may confer advantages in terms of metal chelation in the competitive soil environment due to the additional bidentate hydroxamic functional groups. The metabolites may also fi nd application in various fields including biotechnology, bioremediation, and immuno-PET imaging. IMPORTANCE Iron-chelating siderophores play important roles for their bacterial producers in the environment, but they have also found application in human medicine both in iron chelation therapy to prevent iron overload and in diagnostic imaging, as well as in biotechnology, including as agents for biocontrol of pathogens and bioremediation. In this study, we report the discovery of three novel series of related siderophores, whose biosynthesis depends on the interplay between two NRPS-independent (NIS) pathways in the producing organism S. ambofaciens—the first example to our knowledge of such functional cross-talk. We further reveal that two of these series correspond to acyl-desferrioxamines which incorporate four or five hydroxamate units. Although the biological importance of these novel derivatives is unknown, the increased chelating capacity of these metabolites may find utility in diagnostic imaging (for instance, 89Zr-based immuno-PET imaging) and other applications of metal chelators. [ABSTRACT FROM AUTHOR]

Conventional agriculture practice has heavily relied on chemical fertilizers to increase crop yield. However, long-term application of chemical fertilizers carries tremendous negative impact on the environment and is unsustainable. Hence, the search for an alternative source of fertilizers is required. Orchids are flowers and can be found in tropical countries. The growth and development of orchids are closely tied to the presence of plant growth promoting endophytic microorganisms (PGPM). PGPM harbours various beneficial traits such as potassium and phosphorus solubilization and indole acetic acid and siderophore production which enhance and support plant growth and development. This review article showed that PGPM isolated from orchids could be utilized in conventional agriculture to reduce dependency on chemical fertilizer. [ABSTRACT FROM AUTHOR]

Phyllosphere colonizing antagonistic bacterial isolates were evaluated for managing major rice foliar diseases, namely brown spot caused by Bipolaris oryzae and sheath rot caused by Sarocladium oryzae. Among these various isolates, Pseudomonas aeruginosa isolate 1 effectively inhibited the mycelial growth of B. oryzae and S. oryzae. The volatile compounds of Bacillus subtilis isolates effectively inhibited the mycelial growth of S. oryzae and B. oryzae. Non‐volatile compounds of P. aeruginosa isolate 2 and B. subtilis isolate 1 recorded the maximum inhibition of mycelial growth of B. oryzae and S. oryzae, respectively. P. aeruginosa isolates produced fluorescent pigments and hydrogen cyanide (HCN), whereas isolates of Bacillus spp. did not. All the isolates of P. aeruginosa and Bacillus spp. produced protease enzymes. P. aeruginosa isolates solubilized phosphate, whereas isolates of Bacillus spp. did not. Rice seeds treated with these bacterial suspensions showed improvement in plant growth parameters. The foliar application of two bacterial strains, namely P. aeruginosa isolate 1 + B. subtilis isolate 1 recorded the minimum brown spot and sheath rot disease incidence. Thus, the present showed that phyllosphere colonizing P. aeruginosa and B. subtilis have the potential application for managing foliar fungal diseases of rice plants. [ABSTRACT FROM AUTHOR]

Extended organic polymers such as amorphous Covalent Organic Polymers (COPs) and crystalline Covalent Organic Frameworks (COFs) are emerging functional polymeric materials that have recently been shown promises as luminescent materials for chemosensing applications. A wide variety of luminescence COPs and COFs have been synthesized and successfully used as fluorescence-sensing materials for hazardous environmental pollutants and toxic contaminants. This review exemplifies various COPs and COFs-based fluorescence sensors for selective sensing of Fe(III) ions. The fluorescence sensors are sorted according to their structural features and each section provides a detailed discussion on the synthesis and fluorescence sensing ability of different COPs and COFs towards Fe(III) ions. Also, this review highlights the limitations of the existing organic polymer-based chemosensors and future perspectives on translating COPs and COFs-based fluorescence sensors for the practical detection of Fe(III) ions. [ABSTRACT FROM AUTHOR]

Organic complexation of iron plays a crucial role in preventing its precipitation, facilitating its transport, and modulating its reactivity and bioavailability in natural waters. Although humic substances (HS) complexes serve as the primary source of terrestrial iron reaching ocean waters, the transition from Fe-HS species to other forms of organic complexation with ocean autochthonous ligands has not yet been properly described. Taking advantage of the electrolability of Fe-HS complexes, we monitored the ligand exchange of iron-saturated Suwannee River fulvic and humic acids (SRFA and SRHA) after the addition of desferrioxamine B (DFOB) and other ligands for comparison. We observed that Fe-HS concentrations gradually decreased until reaching an apparent steady state, typical of a reversible reaction within 1 to 15 h. The dissociation kinetics and species partitioning of Fe-SRHS complexes at the equilibrium showed some features contrary to the current paradigm of HS iron complexation. The affinity of SRFA to bind iron is close to that of DFOB and for SRHA is even higher. The heterogeneity of the HS iron binding groups was confirmed, although experiments in NaCl solutions revealed that in seawater it is substantially caused by the interaction of major divalent ions. The different dissociation kinetics of Fe-SRHS complexes obtained with different competing ligands and the absence of Fe-DFOB dissociation in the presence of iron-free SRFA indicate an intimate associative mechanism of ligand exchange, with the presence of a ternary complex (SRHS-Fe-DFOB) that does not form if the departing complex is Fe-DFOB. We hypothesize that at the concentrations of HS and siderophores found in the open ocean, iron ligand exchange is limited and organic iron speciation will be close to being regulated on a "first come, first served" basis. Experiments conducted under saturation of all iron complexes support the formation of a permanent concentration of a ternary complex. Our findings show the real complexity of cation-ligand interactions in seawater, with implications for the interpretation of recent chromatographic and electrochemical measurements and for the understanding of iron partitioning in the presence of ubiquitous HS. [ABSTRACT FROM AUTHOR]

The objective of this paper is to explore the function of the AOL-s00215g415 (Aog415) gene, which encodes for the synthesis of siderophore in the nematode trapping fungal model strain A. oligospora, in order to understand the relationship between siderophore biosynthesis and nematode trapping activity. After a through sequence analysis, it was determined that Aog415 is a siderophore-synthesizing NRPS. The product of this gene was then identified to be the hydroxamate siderophore desferriferrichrome, using mass spectrometry analysis. When compared to the WT strains, the Aog415 knockout strain exhibited a 60% decrease in siderophore content in fermentation broth. Additionally, the number of predatory rings of decreased by 23.21%, while the spore yield increased by 37.34%. The deletion of Aog415 did not affect the growth of A. oligospora in diverse nutrient medium. Lipid metabolism-related pathways were the primary targets of Aog415 disruption as revealed by the metabolomic analysis. In comparison to the WT, a significant reduction in the levels of glycerophospholipids, and glycolipids was observed in the mutation. The metabolic alteration in fatty acyls and amino acid-like molecules were significantly disrupted. The knockout of Aog415 impaired the biosynthesis of the hydroxamate siderophore desferriferrichrome, remodeled the flow of fatty acid in A. oligospora, and mainly reprogrammed the membrane lipid metabolism in cells. Desferriferrichrome, a hydroxamate siderophore affects the growth, metabolism and nematode trapping ability of A. oligospora by regulating iron intake and cell membrane homeostasis. Our study uncovered the significant contribution of siderophores to the growth and nematode trapping ability and constructed the relationship among siderophores biosynthesis, lipid metabolism and nematode trapping activity of A. oligospora, which provides a new insight for the development of nematode biocontrol agents based on nematode trapping fungi. [ABSTRACT FROM AUTHOR]

Simple Summary: Numerous diseases, such as liver abscesses, bacteremias, pneumonia, and urinary tract infections, are caused by Klebsiella pneumonia (K. pneumonia). Historically, immunocompromised patients have been the main target of serious infections induced by K. pneumoniae. However, with the recent appearance and dissemination of hypervirulent strains, healthy individuals have also become susceptible to infection. Moreover, treating K. pneumoniae infections is extremely difficult due to the strains' increased antibiotic resistance. This review summarizes the various virulence factors of this bacterium, especially metallophores. The bacteriology, pathology, and epidemiology of K. pneumonia are also included in this review. The opportunistic pathogen Klebsiella pneumoniae (K. pneumoniae) can colonize mucosal surfaces and spread from mucosae to other tissues, causing fatal infections. Medical equipment and the healthcare setting can become colonized by Klebsiella species, which are widely distributed in nature and can be found in water, soil, and animals. Moreover, a substantial number of community-acquired illnesses are also caused by this organism worldwide. These infections are characterized by a high rate of morbidity and mortality as well as the capacity to spread metastatically. Hypervirulent Klebsiella strains are thought to be connected to these infections. Four components are critical to this bacterium's pathogenicity—the capsule, lipopolysaccharide, fimbriae, and siderophores. Siderophores are secondary metabolites that allow iron to sequester from the surrounding medium and transport it to the intracellular compartment of the bacteria. A number of variables may lead to K. pneumoniae colonization in a specific area. Risk factors for infection include local healthcare practices, antibiotic use and misuse, infection control procedures, nutrition, gender, and age. [ABSTRACT FROM AUTHOR]

The minimal levels of biological-available iron in the environment impose growth limitation on all living organisms. Microbes often secrete high iron-binding- affinity siderophores at high concentrations for scavenging iron from the iron-limited habitats. However, the high prevalence of siderophores released by bacteria into the environment raises an intriguing question whether this chemical cue can be detected by bacterivorous predators. Here, we show that the bacterivorous Caenorhabditis elegans nematode could employ its chemosensory receptor Odr-10 to detect pyoverdine, an iron siderophore secreted by an environmental bacterium, Pseudomonas aeruginosa. This enabled the nematode predator to migrate toward the prey. Our soil microcosm study showed that the detection of pyoverdine and subsequent feeding of P. aeruginosa prey by C. elegans could lead to the expansion of its population. These results showed that siderophores are a prey chemical cue by predators, with key implications in predator-prey interactions. [ABSTRACT FROM AUTHOR]

The gram-negative bacterium Bradyrhizobium japonicum can take up structurally dissimilar ferric siderophores from the environment (xenosiderophores) to meet its nutritional iron requirements. Siderophore-bound iron transported into the periplasm is reduced to the ferrous form by FsrB, dissociated from the siderophore and the free ion is then transported into the cytoplasm by the ferrous iron transporter FeoAB. Here, we identified the RND family exporter genes exsFG and exsH in a selection for secondary site suppressor mutants that restore growth of an fsrB mutant on the siderophores ferrichrome or ferrioxamine. The low level of radiolabel accumulation from 55Fe-labeled ferrichrome or ferrioxamine observed in the fsrB mutant was restored to wild type levels in the fsrB exsG mutant. Moreover, the exsG mutant accumulated more radiolabel from the 55Fe-labeled siderophores than the wild type, but radiolabel accumulation from inorganic 55Fe was similar in the two strains. Thus, ExsFGH exports siderophore-bound iron, but not inorganic iron. The rescued fsrB exsG mutant required feoB for growth, indicating that ExsFGH acts on those siderophores in the periplasm. The exsG mutant was more sensitive to the siderophore antibiotic albomycin than the wild type, whereas the fsrB mutant was more resistant. This suggests ExsFGH normally exports ferrated albomycin. B. japonicum is naturally resistant to many antibiotics. The exsG strain was very sensitive to tetracycline, but not to six other antibiotics tested. We conclude that ExsFGH is a broad substrate exporter that is needed to maintain siderophore homeostasis in the periplasm. [ABSTRACT FROM AUTHOR]

Fungi are important contaminants of historic canvas paintings worldwide. They can grow on both sides of the canvas and decompose various components of the paintings. They excrete pigments and acids that change the visual appearance of the paintings and weaken their structure, leading to flaking and cracking. With the aim of recognizing the most dangerous fungal species to the integrity and stability of paintings, we studied 55 recently isolated and identified strains from historic paintings or depositories, including 46 species from 16 genera. The fungi were categorized as xero/halotolerant or xero/halophilic based on their preference for solutes (glycerol or NaCl) that lower the water activity (aw) of the medium. Accordingly, the aw value of all further test media had to be adjusted to allow the growth of xero/halophilic species. The isolates were tested for growth at 15, 24 °C and 37 °C. The biodeterioration potential of the fungi was evaluated by screening their acidification properties, their ability to excrete pigments and their enzymatic activities, which were selected based on the available nutrients in paintings on canvas. A DNase test was performed to determine whether the selected fungi could utilize DNA of dead microbial cells that may be covering surfaces of the painting. The sequestration of Fe, which is made available through the production of siderophores, was also tested. The ability to degrade aromatic and aliphatic substrates was investigated to consider the potential degradation of synthetic restoration materials. Xerotolerant and moderately xerophilic species showed a broader spectrum of enzymatic activities than obligate xerophilic species: urease, β-glucosidase, and esterase predominated, while obligate xerophiles mostly exhibited β-glucosidase, DNase, and urease activity. Xerotolerant and moderately xerophilic species with the highest degradation potential belong to the genus Penicillium, while Aspergillus penicillioides and A. salinicola represent obligately xerophilic species with the most diverse degradation potential in low aw environments. [ABSTRACT FROM AUTHOR]

Under iron‐limiting conditions, fluorescent pseudomonads acquire iron from the environment by secreting strain‐specific, iron‐chelating siderophores termed pyoverdines (PVD). The rhizosphere bacterium Pseudomonas protegens Pf‐5 produces its own PVD but also can cross‐feed on PVDs produced by other species. Previous work has found that Pf‐5 continues to produce its own PVD when allowed to cross‐feed, raising questions about the benefit of heterologous PVD utilisation. Here, we investigate this question using a defined, unidirectional P. protegens Pf‐5/Pseudomonas aeruginosa PAO1 cross‐feeding model. Quantifying the production of PVD in the presence of heterologous PVD produced by PAO1, we show that cross‐feeding Pf‐5 strains reduce the production of their own PVD, while non‐cross‐feeding Pf‐5 strains increase the production of PVD. Measuring the fitness of cross‐feeding and non‐cross‐feeding Pf‐5 strains in triple coculture with PAO1, we find that cross‐feeding provides a fitness benefit to Pf‐5 when the availability of heterologous PVD is high. We conclude that cross‐feeding can reduce the costs of self‐PVD production and may thus aid in the colonisation of iron‐limited environments that contain compatible siderophores produced by other resident microbes. Taken together, these results expand our understanding of the mechanisms of interspecific competition for iron in microbial communities. [ABSTRACT FROM AUTHOR]

Uropathogenic Escherichia coli (UPEC) secrete multiple siderophore types to scavenge extracellular iron(III) ions during clinical urinary tract infections, despite the metabolic costs of biosynthesis. Here, we find the siderophore enterobactin (Ent) and its related products to be prominent components of the iron-responsive extracellular metabolome of a model UPEC strain. Using defined Ent biosynthesis and import mutants, we identify lower molecular weight dimeric exometabolites as products of incomplete siderophore catabolism, rather than prematurely released biosynthetic intermediates. In E. coli, iron acquisition from iron(III)-Ent complexes requires intracellular esterases that hydrolyze the siderophore. Although UPEC are equipped to consume the products of completely hydrolyzed Ent, we find that Ent and its derivatives may be incompletely hydrolyzed to yield products with retained siderophore activity. These results are consistent with catabolic inefficiency as means to obtain more than one iron ion per siderophore molecule. This is compatible with an evolved UPEC strategy to maximize the nutritional returns from metabolic investments in siderophore biosynthesis. [ABSTRACT FROM AUTHOR]

Discarded electronic materials (e-waste) contain economically valuable metals that can be hazardous to people and the environment. Current e-waste recycling approaches involve either energy-intensive smelting or bioleaching processes that capture metals in their dissolved forms. Our study aimed to use Mn oxidizing fungi for recovering metals from e-waste that could potentially transform recycled metals directly into solid forms. We hypothesized that Mn oxidizing fungi can extract metals through chelation by siderophores and subsequent metal (or metal-chelate) adsorption to Mn oxides produced by fungi. Pure cultures of the three fungal species examined were grown on solidified Leptothrix medium with or without ground lithium ion batteries and incubated under ambient room temperature. The results showed Mn and Co were recovered at the highest concentrations of 8.45% and 1.75%, respectively, when grown with Paraconiothyrium brasiliensis, whereas the greatest concentration of Cu was extracted by Paraphaeosphaeria sporulosa at 20.6% per weight of e-waste-derived metals. Although metal-siderophore complexes were detected in the fungal growth medium, metal speciation data suggested that these complexes only occurred with Fe. This observation suggests that reactions other than complexation with siderophores likely solubilized e-waste metals. Elemental mapping, particularly of P. brasiliensis structures, showed a close association between Mn and Co, suggesting potential adsorption or (co)precipitation of these two metals near fungal mycelium. These findings provide experimental evidence for the potential use of Mn oxidizing fungi in recycling and transforming e-waste metals into solid biominerals. However, optimizing fungal growth conditions with e-waste is needed to improve the efficiency of metal recovery. [ABSTRACT FROM AUTHOR]

Iron is a ubiquitous element on Earth, but despite its abundance in the environment, it remains unavailable to many organisms. An antagonistic bacterium P. brenneri 3.5.1 was screened for the production of siderophores—iron-binding compounds on CAS agar and showed halo zones around the colonies. Bacteria secrete catechol-type siderophores at the concentration of 104 μM after 24 h of cultivation. The production of hydroxamate-type siderophores by P. brenneri 3.5.1 was not detected. The siderophore-containing metabolite fraction of P. brenneri 3.5.1 was extracted and purified. In an antagonistic plate assay, it inhibited the growth of Fusarium oxysporum mycelia in the absence of FeCl3. A complete cluster, containing 17 open reading frames, responsible for the production and export of an enterobactin-like siderophore, is present in the genome of P. brenneri 3.5.1. No other siderophore production genes or their homologues were found in the P. brenneri 3.5.1 genome. Therefore, taking together multiple PGP properties of P. brenneri 3.5.1 and after careful assessment of the biosafety of the strain, it could be considered as a biofungicide against Fusarium oxysporum. [ABSTRACT FROM AUTHOR]

This work is dedicated to the evaluation of the PGP (plant growth promoting) properties of Bacillus pumilus strain 3-19. This strain is a derivative of Bacillus pumilus 7P, a soil isolate that has developed resistance to streptomycin and increased production of certain extracellular hydrolases. The investigation demonstrated that B. pumilus 3-19 proficiently developed biofilms when cultured in liquid medium at 37°C. Siderophore production by strain 3-19 was identified on the Chrome Azurol S (CAS) agar plate, however, not in the liquid medium. The ability of B. pumilus strain 3-19 to accumulate of biosurfactants on different liquid media was investigated. The strain also demonstrated antimicrobial activity against phytopathogenic bacteria Pectobacterium atrosepticum SCRI1043 and Xanthomonas vesicatoria DSM22252. However, no antagonistic activity was found against the phytopathogenic micromycetes Fusarium oxysporum DR57 and Alternaria solani 12RKL15 was found. Therefore, it is important to investigate the plant growth promoting properties of Bacillus pumilus 3-19 when considering using the strain for crop protection, biofertilisers and biopesticides. [ABSTRACT FROM AUTHOR]

Iron participates in various crucial metabolic processes as an essential cofactor of many enzymes, which are vital to the survival of plants and their pathogens. However, excessive iron is toxic to the cells of plants and pathogens. Iron plays a complex role in the interactions between plants and pathogens. Plants and pathogens have evolved sophisticated mechanisms to modulate iron status at a moderate level for maintaining fitness. Iron competition extensively exists on both sides of plants and pathogens during infection. Plants employ iron withholding, local iron accumulation, or iron deficiency to trigger resistance against pathogens. Pathogens counteract host-derived iron stress or interfere with plant iron homeostasis to ensure virulence during infection. This review focuses on the recent progress in understanding the roles of iron in plant-pathogen interactions and proposes prospects for future studies. [ABSTRACT FROM AUTHOR]

Research into marine iron cycles and biogeochemistry has commonly relied on the use of chelators (including siderophores) to manipulate iron bioavailability. To test whether a commonly used chelator, desferrioxamine B (DFB) caused effects beyond changing the iron-status of cells, cultures of the environmentally relevant marine heterotrophic bacterium, Ruegeria pomeroyii, were grown in media with different concentrations of iron and/or DFB, resulting in a gradient of iron availability. To determine how cells responded, transcriptomes were generated for cells from the different treatments and analyzed to determine how cells reacted to these to perturbations. Analyses were also performed to look for cellular responses specific to the presence of DFB in the culture medium. As expected, cells experiencing different levels of iron availability had different transcriptomic profiles. While many genes related to iron acquisition were differentially expressed between treatments, there were many other genes that were also differentially expressed between different sample types, including those related to the uptake and metabolism of other metals as well as genes related to metabolism of other types of molecules like amino acids and carbohydrates. We conclude that while DFB certainly altered iron availability to cells, it also appears to have had a general effect on the homeostasis of other metals as well as influenced metabolic processes outside of metal acquisition. [ABSTRACT FROM AUTHOR]

Our study focuses on hydroxamate-type siderophores from Pseudomonas putida BP25, known for chelating ferric iron and aiding microbial growth in iron-deficient environments. Confirmed through CAS-agar and tetrazolium tests, a purified siderophore extract was obtained via ion-exchange chromatography. Applying varying concentrations of this siderophore to rice seedlings demonstrated concentration-dependent effects on shoot and root phenotypes. Prophylactic application on rice leaves significantly reduced blast severity (68.7%–97.0%), surpassing curative application (47.5%–86.87%). Additionally, the siderophore treatment elevated peroxidase, polyphenol oxidase, and total phenols in rice plants. Defense-related genes linked to salicylic acid (OsPR1.1, OsNPR1 , and OsPDF2.2), and other pathways (Oshox24, OsCLE , and OsGLP3-3, OsEIN2.4 , and OsCSE) promoting blast suppression showed upregulation. However, the OsACS6 gene associated with ethylene-induced internodal elongation was significantly downregulated. Overall, our findings propose that the siderophore from P. putida BP25 induces defense gene transcription, offering potential for sustainable rice production via bio-formulation. [ABSTRACT FROM AUTHOR]

Iron is an essential nutrient for the survival and virulence of Pseudomonas aeruginosa. The pathogen expresses at least 15 different iron‐uptake pathways, the majority involving small iron chelators called siderophores. P. aeruginosa produces two siderophores, but can also use many produced by other microorganisms. This implies that the bacterium expresses appropriate TonB‐dependent transporters (TBDTs) at the outer membrane to import the ferric form of each of the siderophores used. Here, we show that the two α‐carboxylate‐type siderophores rhizoferrin‐Fe and staphyloferrin A‐Fe are transported into P. aeruginosa cells by the TBDT ActA. Among the mixed α‐carboxylate/hydroxamate‐type siderophores, we found aerobactin‐Fe to be transported by ChtA and schizokinen‐Fe and arthrobactin‐Fe by ChtA and another unidentified TBDT. Our findings enhance the understanding of the adaptability of P. aeruginosa and hold significant implications for developing novel strategies to combat antibiotic resistance. [ABSTRACT FROM AUTHOR]

The survival of living organisms depends on iron, one of the most abundant metals in the Earth's crust. Nevertheless, this micronutrient is poorly available in our aerobic atmosphere as well as inside the mammalian host. This problem is circumvented by the expression of high affinity iron uptake machineries, including the production of siderophores, in pathogenic fungi. Here we demonstrated that F. pedrosoi , the causative agent of the neglected tropical disease chromoblastomycosis, presents gene clusters for siderophore production. In addition, ten putative siderophore transporters were identified. Those genes are upregulated under iron starvation, a condition that induces the secretion of hydroxamates, as revealed by chrome azurol S assays. RP-HPLC and mass spectrometry analysis allowed the identification of ferricrocin as an intra- and extracellular siderophore. F. pedrosoi can grow in different iron sources, including the bacterial ferrioxamine B and the host proteins ferritin, hemoglobin and holotransferrin. Of note, addition of hemoglobin, lactoferrin and holotransferrin to the growth medium of macrophages infected with F. pedrosoi enhanced significantly fungal survival. The ability to produce siderophores in iron limited conditions added to the versatility to utilize different sources of iron are strategies that certainly may contribute to fungal survival inside the host. [ABSTRACT FROM AUTHOR]

Background: Currently, clinical laboratories lack an effective method to differentiate between classical Klebsiella pneumoniae (cKP) and hypervirulent Klebsiella pneumoniae (hvKP) strains, leading to delays in diagnosing and treating hvKP infections. Previous studies have identified peg-344, iroB, iucA, prmpA, prmpA2, and siderophores (SP) yields greater than 30 μg/ml as reliable markers for distinguishing hvKP from cKp strains. However, these diagnostic tests were conducted on a relatively small study population and lacked sufficient clinical data support. In this study, hvKP strains were identified by biomarker analysis and the Galleria mellonella model. Combined with in vitro and in vivo experiments, the reliability of clinical identification method of hvKP was verified, which provided an experimental basis for timely diagnosis of hvKP infection. Results: According to the clinical data, a total of 108 strains of hvKP were preliminary screened. Among them, 94 strains were further identified using PCR analysis of biomarkers and quantitative determination of SP. The high virulence of hvKP was subsequently confirmed through infection experiments on Galleria mellonella. Additionally, susceptibility testing revealed the identification of 58 carbapenem-resistant hvKP (CR-hvKP) strains and 36 carbapenem-sensitive hvKP (CS-hvKP) strains. By comparing molecular diagnostic indexes, molecular characteristics such as high SP production of CR-hvKP were found. Conclusion: The combination of clinical data and molecular diagnostic index analysis effectively enables the identification of hvKP, particularly CR-hvKP. This study provides a scientific basis for accurate clinical identification and timely treatment of hvKP. [ABSTRACT FROM AUTHOR]

The Escherichia marmotae is a bacterium of the Enterobacterales order, which was first isolated from the Himalayan marmot (Marmota himalayana). Recently E. marmotae has been shown to cause severe infections in humans. Wild animals were suggested to be a natural reservoir of this bacterium. The present study describes the first case of E. marmotae isolation from an apparently healthy wild bank vole (Myodes glareolus). Phenotype, as well as genotype-based techniques, were applied to characterize E. marmotae M-12 isolate. E. marmotae M-12 had the capsule-positive phenotype, high adhesion to human erythrocytes and HEp-2 cells as well as a low invasion into HEp-2 cells. E. marmotae M-12 was avirulent in mice. The phylogenomic analyses of E. marmotae showed dispersed phylogenetic structure among isolates of different origins. Virulome analysis of M-12 isolate revealed the presence of the following factors: siderophores, heme uptake systems, capsule synthesis, curli and type I fimbriae, flagella proteins, OmpA porin, etc. Comparative virulome analysis among available E. marmotae genomes revealed the presence of capsule K1 genes mostly in pathogenic isolates and OmpA porin presence among all strains. We assume that the K1 capsule and OmpA porin play a key role in the virulence of E. marmotae. Pathogenesis of the latter might be similar to extraintestinal pathogenic E. coli. [ABSTRACT FROM AUTHOR]

Siderophores are low-molecular-weight secondary metabolites that function as iron chelators. Under iron-deficiency conditions, they are produced by a wide variety of microbes, allowing them to increase their iron uptake. The primary function of these compounds is the environmental iron scavenging and its transport into the cytosol. Iron is then reduced to its ferrous form to operate as an enzymatic cofactor for various functions, including respiration, nitrogen fixation, photosynthesis, methanogenesis, and amino acid synthesis. Depending on their functional group, siderophores are classified into hydroxamate, catecholate, phenolate, carboxylate, and mixed types. They have achieved great importance in recent years due to their medical applications as antimicrobial, antimalarial, or anticancer drugs, vaccines, and drug-delivery agents. This review integrates current advances in specific healthcare applications of microbial siderophores, delineating new opportunities and challenges as viable therapies to fight against diseases that represent crucial public health problems in the medical field. Key points • Siderophores are low-molecular-weight secondary metabolites functioning as iron chelators. • The siderophore's properties offer viable options to face diverse clinical problems. • Siderophores are alternatives for the enhancement of antibiotic activities. [ABSTRACT FROM AUTHOR]

We, herein, report the synthesis of 13C2‐labeled natural products from the mugineic acid and avenic acid family. These phytosiderophores ("plant iron carriers") are built up from non‐proteinogenic amino acids and play a key role in micronutrient uptake in gramineous plants. In this work, two central building blocks are prepared from labeled starting materials (13C2‐bromoacetic acid, 13C2‐glycine) and further employed in our recently reported divergent, branched synthetic strategy delivering eight isotopically labeled phytosiderophores. The required labeled building blocks (13C2‐l‐allylglycine and a related hydroxylated derivative) were prepared via enantioselective phase‐transfer catalysis and enantio‐ and diastereoselective aldol condensation with a chiral auxiliary, respectively, both potentially valuable themselves for other synthetic routes toward labeled (natural) products. [ABSTRACT FROM AUTHOR]

Important bacterial pathogens such as Pseudomonas aeruginosa produce several exoproducts such as siderophores, degradative enzymes, biosurfactants, and exopolysaccharides that are used extracellularly, benefiting all members of the population, hence being public goods. Since the production of public goods is a cooperative trait, it is in principle susceptible to cheating by individuals in the population who do not invest in their production, but use their benefits, hence increasing their fitness at the expense of the cooperators' fitness. Among the most studied virulence factors susceptible to cheating are siderophores and exoproteases, with several studies in vitro and some in animal infection models. In addition to these two well-known examples, cheating with other virulence factors such as exopolysaccharides, biosurfactants, eDNA production, secretion systems, and biofilm formation has also been studied. In this review, we discuss the evidence of the susceptibility of each of those virulence factors to cheating, as well as the mechanisms that counteract this behavior and the possible consequences for bacterial virulence. [ABSTRACT FROM AUTHOR]

The co-culturing of microorganisms is a well-known strategy to study microbial interactions in the laboratory. This approach facilitates the identification of new signals and molecules produced by one species that affects other species' behavior. In this work, we have studied the effects of the interaction of nine Streptomyces species (S. albidoflavus, S. ambofaciens, S. argillaceus, S. griseus, S. lividans, S. olivaceus, S. parvulus, S. peucetius, and S. rochei) with the predator bacteria Myxococcus xanthus, five of which (S. albidoflavus, S. griseus, S. lividans, S. olivaceus, and S. argillaceus) induce mound formation of M. xanthus on complex media (Casitone Yeast extract (CYE) and Casitone tris (CTT); media on which M. xanthus does not form these aggregates under normal culture conditions. An in-depth study on S. griseus–M. xanthus interactions (the Streptomyces strain producing the strongest effect) has allowed the identification of two siderophores produced by S. griseus, demethylenenocardamine and nocardamine, responsible for this grouping effect over M. xanthus. Experiments using pure commercial nocardamine and different concentrations of FeSO4 show that iron depletion is responsible for the behavior of M. xanthus. Additionally, it was found that molecules, smaller than 3 kDa, produced by S. peucetius can induce the production of DK-xanthenes by M. xanthus. [ABSTRACT FROM AUTHOR]

Background: Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O-TRENSOX and O-TRENOX two synthetic siderophores would be good candidates for this purpose as they are hexadentate ligands based on the very versatile and efficient 8-hydroxyquinoline chelating subunit. First, the radiolabeling of O-TRENOX and O-TRENSOX with 99mTc was investigated. Different parameters such as the quantity of chelating agent, type of reducing agent, pH and temperature of the reaction mixture were adjusted in order to find the best radiolabeling conditions. Then an assessment of the partition coefficient by measuring the distribution of each radiosynthesized complex between octanol and phosphate-buffered saline was realized. The complex's charge was evaluated on three different celluloses (neutral, negatively charged P81 and positively charged DE81), and finally in vivo studies with biodistribution and SPECT imaging of [99mTc]Tc-O-TRENOX and [99mTc]Tc-O-TRENSOX were performed. Results: The radiolabeling studies showed a rapid and efficient complexation of 99mTc with both chelating agents. Using tin pyrophosphate as the reducing agent and a minimum of 100 nmol of ligand, we obtained the [99mTc]Tc-O-TRENOX complex with a radiochemical purity of more than 98% and the [99mTc]Tc-O-TRENSOX complex with one above 97% at room temperature within 5 min. [99mTc]Tc-O-TRENOX complex was lipophilic and neutral, leading to a hepatobiliary elimination in mice. On the contrary, the [99mTc]Tc-O-TRENSOX complex was found to be hydrophilic and negatively charged. This was confirmed by a predominantly renal elimination in mice. Conclusions: These encouraging results allow us to consider the O-TRENOX/99mTc and O-TRENSOX/99mTc complexes as serious candidates for SPECT imaging chelators. This study should be continued by conjugating these tris-oxine ligands to peptides or antibodies and comparing them with the other bifunctional agents used with Tc. [ABSTRACT FROM AUTHOR]

Invasive fungal infections have become a major challenge for public health, mainly due to the growing numbers of immunocompromised patients, with high morbidity and mortality. Currently, conventional imaging modalities such as computed tomography and magnetic resonance imaging contribute largely to the noninvasive diagnosis and treatment evaluation of those infections. These techniques, however, often fall short when a fast, noninvasive and specific diagnosis of fungal infection is necessary. Molecular imaging, especially using nuclear medicine-based techniques, aims to develop fungal-specific radiotracers that can be tested in preclinical models and eventually translated to human applications. In the last few decades, multiple radioligands have been developed and tested as potential fungal-specific tracers. These include radiolabeled peptides, antifungal drugs, siderophores, fungal-specific antibodies, and sugars. In this review, we provide an overview of the pros and cons of the available radiotracers. We also address the future prospects of fungal-specific imaging. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the potential of Aspergillus tubingensis in extracting metals from rocks simulating Martian regolith through biomining. The results indicated that the fungal strain produced organic acids, particularly oxalic acid, in the first five days, leading to a rapid reduction in the pH of the culture medium. This acidic medium is ideal for bioleaching, a process that employs acidolysis and complexolysis to extract metals from rocks. Additionally, the strain synthesized siderophores, molecules capable of mobilizing metals from solid matrices, as verified by the blue CAS colorimetric test. The secretion of siderophores in the culture medium proved advantageous for biomining. The siderophores facilitated the leaching of metal ions, such as manganese, from the rock matrix into the acidified water solution. In addition, the susceptibility of the Martian regolith simulant to the biomining process was assessed by determining the particle size distribution, acid composition after treatment, and geochemical composition of the rock. Although the preliminary results demonstrate successful manganese extraction, further research is required to optimize the extraction technique. To conclude, the A. tubingensis strain exhibits promising abilities in extracting metals from rocks through biomining. Its use could prove useful in future in situ mining operations and environmental remediation efforts. Further research is required to optimize the process and evaluate its feasibility on a larger scale. [ABSTRACT FROM AUTHOR]

The current study was aimed to isolate and identify Fluorescent Pseudomonads from Erbil soil and then screening for Siderophores biosynthesis genes. Soil samples were collected from different location in Erbil governorate. A total of 18 isolates of Pseudomonas fluorescens were isolated on enriched and selective King B medium and they identified using API20E, Vitek2 morphological features, cultural, biochemical characteristics, and 16S rRNA gene sequencing technique. Plant growth promoting traits of the isolates were also studied such as IAA, siderophore and HCN production. All isolates exhibited high potential of IAA, HCN and siderophore production. We selected different isolate for screen the presence of Iron solubilizing gene using specific primers with PCR technique. All isolates resolute for their iron solubilizing efficiency and all of them showed iron solubilizing activity. Isolate (Cpf3) were the most efficient isolate, while (Dpf16) were the least efficient isolates in Fe-solubilization. psiB and psiG genes were selected to screen for the presence of iron solubilizing using specific primers with PCR technique. The results showed positive reactions and all isolates contained iron solubilizing genes. [ABSTRACT FROM AUTHOR]

Calicotome villosa is a eurioic legume with broad distribution in the south of Europe. It can grow in almost any type of soil as well as in humid and dry and nutrient-deficient ecosystems. The broad distribution and eurioic nature of C. villosa may be attributed to its ability to establish endophytic associations with plant-growth-promoting (PGP) bacteria housed in the nodules and rootlets. This study examined the legume–microbe interaction of C. villosa growing in two contrasting locations: a hilltop with high sun irradiance and drought, and a valley bottom with a low level of radiation and sufficient soil humidity for plant growth. Calicotome villosa adult plants established endophytic interactions with bacteria in six genera: Pseudomonas, Stenotrophomonas, Bacillus, Paenibacillus, Brevicacterium, and Rhizobium. Plants growing on the hilltop had associated lower bacterial richness than those grown on the valley bottom. All strains were drought-tolerant and produced siderophores, IAA, HCN, and NH3 that stimulated plant performance in C. villosa plants and the other four legumes commonly present in the understory of the shrub communities. The legumes' capacity to selectively host symbiotic bacteria that enhance plant survival in harsh conditions partly accounts for the diverse partnerships between C. villosa plants and their symbionts, ultimately explaining the wide distribution of this plant species. [ABSTRACT FROM AUTHOR]

A series of new conjugates comprised from a small synthetic antimicrobial peptide (AMP) and a siderophore‐type vector component was designed and tested for activity on P. aeruginosa PAO1 and several genetically modified strains. As AMP, the well‐established arginine‐tryptophane combination K(RW)3 (P1) was chosen with an added lysine for siderophore attachment. This peptide is easy to prepare, modify, and possesses good anti‐bacterial activity. On the vector part, we examined several moieties: (i) the natural siderophore deferoxamine (DFO); (ii) bidentate iron chelators based on the hydroxamate building block (4 a–c) ; (iii) the non‐siderophore chelators deferasirox (DFX) and deferiprone‐carboxylate (DFP‐COOH). All conjugates were prepared by solid phase synthesis techniques and fully characterized by HPLC and mass spectrometry (including HR‐MS). 55Fe uptake assays indicate a receptor‐mediated uptake for 4 a–c, DFP‐COOH and DFO, which is dependent on the outer membrane transporter FoxA in the case of DFO. All conjugates showed increased antibacterial activity against P. aeruginosa compared to the parent peptide P1 alone when investigated in iron‐depleted medium. MIC values were as low as 2 μM (for P1‐DFP) on wild type P. aeruginosa. The activity of P1‐DFO and P1‐DFP was even better on genetically mutated strains unable to produce siderophores (down to 0.5 μM). Although the DFX vector on its own was not able to transport iron inside the bacterial cell as shown by 55Fe uptake studies, the P1‐DFX conjugate had excellent antibacterial activity compared to P1 (2 μM, and as low as 0.25 μM on a receptor‐deficient strain unable to produce siderophores), suggesting that the conjugates were indeed recognized and internalized by an (unknown) transporter. Control experiments with an equimolar mixture of P1 and DFX confirm that the observed activity is intrinsic to vectorization. This work thus demonstrates the power of linking small AMPs covalently to siderophores for a new class of Trojan Horse antibiotics, with P1‐DFP and P1‐DFX being the most potent conjugates. [ABSTRACT FROM AUTHOR]

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 (Fe2+) and ferric (Fe3+). These two oxidation states are interconvertible by redox reactions and form complexes with a wide range of siderophores. At neutral pH in soil, Fe2+ is highly soluble upto 100 mM but have less biological value, whereas Fe3+ is less soluble upto 10–9 M. This reduced bioavailability of Fe3+ induces competition among microorganisms. As many microorganisms need at least 10–6 M of Fe3+ form of iron for their growth, siderophores from these microbes readily withdraw Fe3+ 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. [ABSTRACT FROM AUTHOR]

Iron uptake during infection is an essential pathogenicity factor of several bacteria, including Tenacibaculum dicentrarchi, an emerging pathogen for salmonid and red conger eel (Genypterus chilensis) farms in Chile. Iron‐related protein families were recently found in eight T. dicentrarchi genomes, but biological studies have not yet confirmed functions. The investigation reported herein clearly demonstrated for the first time that T. dicentrarchi possesses different systems for iron acquisition—one involving the synthesis of siderophores and another allowing for the utilization of heme groups. Using 38 isolates of T. dicentrarchi and the type strain CECT 7612T, all strains grew in the presence of the chelating agent 2.2′‐dipyridyl (from 50 to 150 μM) and produced siderophores on chrome azurol S plates. Furthermore, 37 of the 38 T. dicentrarchi isolates used at least four of the five iron sources (i.e. ammonium iron citrate, ferrous sulfate, iron chloride hexahydrate, haemoglobin and/or hemin) when added to iron‐deficient media, although the cell yield was less when using hemin. Twelve isolates grew in the presence of hemin, and 10 of them used only 100 μM. Under iron‐supplemented or iron‐restricted conditions, whole cells of three isolates and the type strain showed at least one membrane protein induced in iron‐limiting conditions (c.a. 37.9 kDa), regardless of the isolation host. All phenotypic results were confirmed by in‐silico genomic T. dicentrarchi analysis. Future studies will aim to establish a relationship between iron uptake ability and virulence in T. dicentrarchi through in vivo assays. [ABSTRACT FROM AUTHOR]

The Escherichia marmotae is a bacterium of the Enterobacterales order, which was first isolated from the Himalayan marmot (Marmota himalayana). Recently E. marmotae has been shown to cause severe infections in humans. Wild animals were suggested to be a natural reservoir of this bacterium. The present study describes the first case of E. marmotae isolation from an apparently healthy wild bank vole (Myodes glareolus). Phenotype, as well as genotype-based techniques, were applied to characterize E. marmotae M-12 isolate. E. marmotae M-12 had the capsule-positive phenotype, high adhesion to human erythrocytes and HEp-2 cells as well as a low invasion into HEp-2 cells. E. marmotae M-12 was avirulent in mice. The phylogenomic analyses of E. marmotae showed dispersed phylogenetic structure among isolates of different origins. Virulome analysis of M-12 isolate revealed the presence of the following factors: siderophores, heme uptake systems, capsule synthesis, curli and type I fimbriae, flagella proteins, OmpA porin, etc. Comparative virulome analysis among available E. marmotae genomes revealed the presence of capsule K1 genes mostly in pathogenic isolates and OmpA porin presence among all strains. We assume that the K1 capsule and OmpA porin play a key role in the virulence of E. marmotae. Pathogenesis of the latter might be similar to extraintestinal pathogenic E. coli. [ABSTRACT FROM AUTHOR]

The present work was focused on plant growth-promoting bacteria (PGPB) for the enhanced production of tomatoes. The effect of 14 indigenous PGPB isolated from the soil samples collected from Gir National forest areas (Dist. Junagadh, Gujarat, India) and the coastal region of Saurashtra (Dist. Gir-Somnath, Gujarat, India) on tomato seedlings was studied. Only 6 isolates showed positive results in in vitro biochemical and plant-growth-promoting assays such as phosphate and zinc solubilization, siderophores and HCN production and antibacterial and antifungal properties. The rest isolates were negative to one or more of the selected tests. Based on in vitro results, all PGPB were tested on tomato seedlings. Four stage screenings were used to select the best combinations. After the primary screening, 9 isolates were selected for further experiments based on the germination, height of plants and seedling vigor. Plant height, leaf count, seedling vigor and total chlorophyll were measured. Leaf anatomy was studied at the end of the quaternary trial to understand the changes at a cellular level and it revealed the anatomical changes such as increased chlorophyll at cellular level and enhanced starch production. Microbial consortia showed better results compated to single-inoculant treatment. Out of 503 different combinations tested at secondary trial, 129 were selected for tertiary trials and 24 from them were further qualified for quaternary trials. At the end of quaternary trials, total 04 combinations were selected for future experiments on field. The quaternary trial strategy helped to reduce the total 503 possible combinations to 04 combinations improving germination, height, seedling vigor, number of leaves and chlorophyll content compared to non-treated tomato plants. Further trials were carried out in field for long period of time to measure the profound effect of selected consortium in real life. [ABSTRACT FROM AUTHOR]

Infections with multidrug‐resistant Gram‐negative bacteria constitute a silent pandemic threat that is increasing globally. A major technical and scientific hurdle hampering the development of efficient antibiotics against Gram‐negative species is the low permeability of their outer membrane that prevents the entry of most small molecules into the cells. This can be overcome by targeting active iron transport systems of the pathogens in a Trojan‐Horse strategy that makes use of drug‐loaded artificial siderophores. While we utilized catechols as iron‐binding motifs in previous work, this study reports the design, synthesis and characterization of siderophores with a DOTAM scaffold that was substituted with three hydroxamate arms allowing for a hexacoordination of iron. Their iron‐chelating capabilities were shown colorimetrically, and the ability of compound 1 to deliver iron into Escherichia coli in a chelation‐specific manner was proven by a growth recovery assay. A covalent siderophore‐ciprofloxacin conjugate exerted antibiotic effects against E. coli, albeit it was less potent than the free drug. The study qualifies artificial DOTAM siderophores with hydroxamate binders as scaffolds for bacterial Trojan Horses. This contribution for honoring my mentor Helmut Schwarz echoes two motifs of my work with him: Hydroxylamin, the topic of my first paper ever, and the fascinating properties of iron ions, studied in the gas phase during my Ph.D. Thesis, became a core subject of our current chemical biology research on antiinfectives. [ABSTRACT FROM AUTHOR]

Cucumber Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerinum seriously affects the sustainable development of the cucumber industry. In order to obtain high-efficiency antagonistic Bacillus spp. against cucumber Fusarium wilt and clarify its growth-promoting effect, hte biocontrol strain with a strong antagonistic effect against F. oxysporum were screened from Bacillus with a certain resistance to Fusarium solan, and its morphological, physiological and biochemical, genetic characteristics and plant growth-promoting characteristics were evaluated. The results showed that strain N1、N3 and N6 presented significant inhibitory effects on F. oxysporum, with inhibitory rates of 77.71%, 75.94% and 74.76%, respectively. Three strains were all identified as Bacillus velezensis, all the three strains showed releasing potassium ability, and produced protease, chitinase, pectinase and siderophores. In the seedlings disease-prevention and growth-promotion test, the disease index of inoculated strain N1, N3 and N6 significantly reduced, the control efficiency was 41.93%, 20.97%, and 66.13% respectively on the 18th day after inoculation. Inoculation with N1, N3 and N6 strains effectively promoted the growths of cucumber seedlings compared with single inoculation of F. oxysporum f. sp. treatment, including plant height, stem thickness, leaf area, chlorophyll content and aboveground and subsurface fresh weight, the growth promoting effect of N6 treatment was the most significant. It increased by 21.56%, 56.13%, 47.95%, 76.18%, 222.89% and 70% respectively. Compared with the control, the growth characteristics of treated plants significantly decreased except for the fresh weight of underground parts. Under inoculation F. oxysporum f. sp., the addition of N6 significantly increased the stem thickness and aboveground fresh weight. In conclusion, N6 can be used as potential biocontrol resources to control cucumber Fusarium wilt caused by F. oxysporum f. sp. cucumerinum and promote the growth of seedlings for sustainable and efficient cucumber production. [ABSTRACT FROM AUTHOR]

Chemical communication between competing bacteria in multi‐species environments often enables both species to adapt and survive, and perhaps even thrive. P. aeruginosa and S. aureus are two bacterial pathogens found in natural biofilms, especially in the lungs of cystic fibrosis (CF) patients, where recent studies showed that there is often cooperation between the two species, leading to increased disease severity and antibiotic resistance. However, the mechanisms behind this cooperation are poorly understood. In this study, we analyzed co‐cultured biofilms in various settings, and we applied untargeted mass spectrometry‐based metabolomics analyses, combined with synthetic validation of candidate compounds. We unexpectedly discovered that S. aureus can convert pyochelin into pyochelin methyl ester, an analogue of pyochelin with reduced affinity for iron (III). This conversion allows S. aureus to coexist more readily with P. aeruginosa and unveils a mechanism underlying the formation of robust dual‐species biofilms. [ABSTRACT FROM AUTHOR]

Chemical communication between competing bacteria in multi‐species environments often enables both species to adapt and survive, and perhaps even thrive. P. aeruginosa and S. aureus are two bacterial pathogens found in natural biofilms, especially in the lungs of cystic fibrosis (CF) patients, where recent studies showed that there is often cooperation between the two species, leading to increased disease severity and antibiotic resistance. However, the mechanisms behind this cooperation are poorly understood. In this study, we analyzed co‐cultured biofilms in various settings, and we applied untargeted mass spectrometry‐based metabolomics analyses, combined with synthetic validation of candidate compounds. We unexpectedly discovered that S. aureus can convert pyochelin into pyochelin methyl ester, an analogue of pyochelin with reduced affinity for iron (III). This conversion allows S. aureus to coexist more readily with P. aeruginosa and unveils a mechanism underlying the formation of robust dual‐species biofilms. [ABSTRACT FROM AUTHOR]