Plants, Microorganisms and Their Metabolites in Supporting Asbestos Detoxification-A Biological Perspective in Asbestos Treatment.

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.

Genomic insights and anti-phytopathogenic potential of siderophore metabolome of endolithic Nocardia mangyaensis NH1.

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.

Rhodotorulic Acid and its Derivatives: Synthesis, Properties, and Applications.

Siderophores are low molecular weight compounds produced by microorganisms to scavenge iron in iron-deficient environments. Rhodotorulic acid, a natural hydroxamate siderophore, plays a vital role in iron acquisition for fungi and bacteria. As the simplest natural hydroxamate siderophore, it exhibits a high affinity for ferric ions, enabling it to form stable complexes that facilitate iron uptake and transport within microorganisms. This article provides a comprehensive analysis of this hydroxamate siderophore, rhodotorulic acid, its synthesis, physicochemical properties, and biological significance. It also explores its applications in antifungal and plant protection strategies. Insights into RA derivatives reveal distinct biological effects and applications with potential in various fields, from antioxidants to antifungals. Rhodotorulic acid and its derivatives show promise for novel therapies, plant protection strategies, and iron supplementation in agriculture. Understanding their properties could advance science and medicine with sustainable practices.

The emergence of cefiderocol resistance in Pseudomonas aeruginosa from a heteroresistant isolate during prolonged therapy.

Cefiderocol is a siderophore cephalosporin designed to target multi-drug-resistant Gram-negative bacteria. Previously, the emergence of cefiderocol non-susceptibility has been associated with mutations in the chromosomal cephalosporinase (PDC) along with mutations in the PirA and PiuA/D TonB-dependent receptor pathways. Here, we report a clinical case of cefiderocol-resistant P. aeruginosa that emerged in a patient during treatment. This resistance was associated with mutations not previously reported, suggesting potential novel pathways to cefiderocol resistance.

In vitro phenotypic evidence for the utilization of iron from different sources and siderophores production in the fish pathogen Tenacibaculum dicentrarchi.

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.

Plant Growth-Promoting Rhizobacteria for Sustainable Agricultural Production.

Rhizosheric bacteria with several abilities related to plant growth and health have been denominated Plant Growth-Promoting Rhizobacteria (PGPR). PGPR promote plant growth through several modes of action, be it directly or indirectly. The benefits provided by these bacteria can include increased nutrient availability, phytohormone production, shoot and root development, protection against several phytopathogens, and reduced diseases. Additionally, PGPR can help plants to withstand abiotic stresses such as salinity and drought and produce enzymes that detoxify plants from heavy metals. PGPR have become an important strategy in sustainable agriculture due to the possibility of reducing synthetic fertilizers and pesticides, promoting plant growth and health, and enhancing soil quality. There are many studies related to PGPR in the literature. However, this review highlights the studies that used PGPR for sustainable production in a practical way, making it possible to reduce the use of fertilizers such as phosphorus and nitrogen and fungicides, and to improve nutrient uptake. This review addresses topics such as unconventional fertilizers, seed microbiome for rhizospheric colonization, rhizospheric microorganisms, nitrogen fixation for reducing chemical fertilizers, phosphorus solubilizing and mineralizing, and siderophore and phytohormone production for reducing the use of fungicides and pesticides for sustainable agriculture.

Bacillibactin class siderophores produced by the endophyte Bacillus subtilis NPROOT3 as antimycobacterial agents.

The bacterial endophytes isolated from the halophyte Salicornia brachiata were explored for the antimicrobial potential to discover novel microbial inhibitors that combat multidrug resistance. Upon investigation, ethyl acetate extract of the endophyte Bacillus subtilis NPROOT3 displayed significant potency against Mycobacterium smegmatis MTCC6 as well as Mycobacterium tuberculosis H37Rv strain. Further investigation of ethyl acetate crude extract by repeated chromatographic separations followed by characterization using UV, HR-ESI-MS, MALDI-MS, MALDI-MS/MS, CD, and NMR spectroscopy yielded a series of five known siderophores, namely, SVK21 (1), bacillibactin C (2), bacillibactin B (3), tribenglthin A (4), and bacillibactin (5). A total of two out of five compounds, 4 (MIC 38.66 µM) and 5 (MIC 22.15 µM) exhibited significant inhibition against the strain M. smegmatis MTCC6 comparable with positive control rifampicin (MIC 12.15 µM). None of these five bacillibactin molecules are previously reported to exhibit bioactivity against Mycobacterium sp. Herein for the first time, all the compounds were screened for their antibacterial activities against a panel of bacterial pathogens of humans. Furthermore, the probable mechanism of action of bacillibactin compounds for their antimycobacterial activity is also discussed. The findings of this study open up a new chemotype for inhibition of the Mycobacterium sp. and other multidrug-resistant pathogens.

Siderophore-Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells.

Due to rising resistance, new antibacterial strategies are needed, including methods for targeted antibiotic release. As targeting vectors, chelating molecules called siderophores that are released by bacteria to acquire iron have been investigated for conjugation to antibacterials, leading to the clinically approved drug cefiderocol. The use of small-molecule catalysts for prodrug activation within cells has shown promise in recent years, and here we investigate siderophore-linked ruthenium catalysts for the activation of antibacterial prodrugs within cells. Moxifloxacin-based prodrugs were synthesised, and their catalyst-mediated activation was demonstrated under anaerobic, biologically relevant conditions. In the absence of catalyst, decreased antibacterial activities were observed compared to moxifloxacin versus Escherichia coli K12 (BW25113). A series of siderophore-linked ruthenium catalysts were investigated for prodrug activation, all of which displayed a combinative antibacterial effect with the prodrug, whereas a representative example displayed little toxicity against mammalian cell lines. By employing complementary bacterial growth assays, conjugates containing siderophore units based on catechol and azotochelin were found to be most promising for intracellular prodrug activation.

In vivo localization of iron starvation induced proteins under variable iron supplementation regimes in Phaeodactylum tricornutum.

The model pennate diatom Phaeodactylum tricornutum is able to assimilate a range of iron sources. It therefore provides a platform to study different mechanisms of iron processing concomitantly in the same cell. In this study, we follow the localization of three iron starvation induced proteins (ISIPs) in vivo, driven by their native promoters and tagged by fluorophores in an engineered line of P. tricornutum. We find that the localization patterns of ISIPs are dynamic and variable depending on the overall iron status of the cell and the source of iron it is exposed to. Notwithstanding, a shared destination of the three ISIPs both under ferric iron and siderophore-bound iron supplementation is a globular compartment in the vicinity of the chloroplast. In a proteomic analysis, we identify that the cell engages endocytosis machinery involved in the vesicular trafficking as a response to siderophore molecules, even when these are not bound to iron. Our results suggest that there may be a direct vesicle traffic connection between the diatom cell membrane and the periplastidial compartment (PPC) that co-opts clathrin-mediated endocytosis and the "cytoplasm to vacuole" (Cvt) pathway, for proteins involved in iron assimilation. Proteomics data are available via ProteomeXchange with identifier PXD021172. Highlight: The marine diatom P. tricornutum engages a vesicular network to traffic siderophores and phytotransferrin from the cell membrane directly to a putative iron processing site in the vicinity of the chloroplast.

Siderophore Immunization Restricted Colonization of Adherent-Invasive Escherichia coli and Ameliorated Experimental Colitis.

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal tract and profound alterations to the gut microbiome. Adherent-invasive Escherichia coli (AIEC) is a mucosa-associated pathobiont that colonizes the gut of patients with Crohn's disease, a form of IBD. Because AIEC exacerbates gut inflammation, strategies to reduce the AIEC bloom during colitis are highly desirable. To thrive in the inflamed gut, Enterobacteriaceae acquire the essential metal nutrient iron by producing and releasing siderophores. Here, we implemented an immunization-based strategy to target the siderophores enterobactin and its glucosylated derivative salmochelin to reduce the AIEC bloom in the inflamed gut. Using chemical (dextran sulfate sodium) and genetic (Il10-/- mice) IBD mouse models, we showed that immunization with enterobactin conjugated to the mucosal adjuvant cholera toxin subunit B potently elicited mucosal and serum antibodies against these siderophores. Siderophore-immunized mice exhibited lower AIEC gut colonization, diminished AIEC association with the gut mucosa, and reduced colitis severity. Moreover, Peyer's patches and the colonic lamina propria harbored enterobactin-specific B cells that could be identified by flow cytometry. The beneficial effect of siderophore immunization was primarily B cell-dependent because immunized muMT-/- mice, which lack mature B lymphocytes, were not protected during AIEC infection. Collectively, our study identified siderophores as a potential therapeutic target to reduce AIEC colonization and its association with the gut mucosa, which ultimately may reduce colitis exacerbation. Moreover, this work provides the foundation for developing monoclonal antibodies against siderophores, which could provide a narrow-spectrum strategy to target the AIEC bloom in Crohn's disease patients. IMPORTANCE Adherent-invasive Escherichia coli (AIEC) is abnormally prevalent in patients with ileal Crohn's disease and exacerbates intestinal inflammation, but treatment strategies that selectively target AIEC are unavailable. Iron is an essential micronutrient for most living organisms, and bacterial pathogens have evolved sophisticated strategies to capture iron from the host environment. AIEC produces siderophores, small, secreted molecules with a high affinity for iron. Here, we showed that immunization to elicit antibodies against siderophores promoted a reduction of the AIEC bloom, interfered with AIEC association with the mucosa, and mitigated colitis in experimental mouse models. We also established a flow cytometry-based approach to visualize and isolate siderophore-specific B cells, a prerequisite for engineering monoclonal antibodies against these molecules. Together, this work could lead to a more selective and antibiotic-sparing strategy to target AIEC in Crohn's disease patients.

Physiological and Transcriptome Analyses Revealed the Mechanism by Which Deferoxamine Promotes Iron Absorption in Cinnamomum camphora.

Iron deficiency causes chlorosis and growth inhibition in Cinnamomum camphora, an important landscaping tree species. Siderophores produced by plant growth-promoting rhizobacteria have been widely reported to play an indispensable role in plant iron nutrition. However, little to date has been determined about how microbial siderophores promote plant iron absorption. In this study, multidisciplinary approaches, including physiological, biochemical and transcriptome methods, were used to investigate the role of deferoxamine (DFO) in regulating Fe availability in C. camphora seedlings. Our results showed that DFO supplementation significantly increased the Fe2+ content, SPAD value and ferric-chelate reductase (FCR) activity in plants, suggesting its beneficial effect under Fe deficiency. This DFO-driven amelioration of Fe deficiency was further supported by the improvement of photosynthesis. Intriguingly, DFO treatment activated the metabolic pathway of glutathione (GSH) synthesis, and exogenous spraying reduced glutathione and also alleviated chlorosis in C. camphora. In addition, the expression of some Fe acquisition and transport-related genes, including CcbHLH, CcFRO6, CcIRT2, CcNramp5, CcOPT3 and CcVIT4, was significantly upregulated by DFO treatment. Collectively, our data demonstrated an effective, economical and feasible organic iron-complexing agent for iron-deficient camphor trees and provided new insights into the mechanism by which siderophores promote iron absorption in plants.

De novo synthesis of ferrichrome by Fusarium oxysporum f. sp. cubense TR4 in response to iron starvation.

Manipulation of iron bioavailability in the banana rhizosphere may suppress Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc). However, iron starvation induced by application of synthetic iron chelators does not effectively suppress Fusarium wilt. It is unclear whether Foc can subvert iron chelators and thereby evade iron starvation through the synthesis of iron-scavenging secondary metabolites, called siderophores. In vitro studies were conducted using iron-deficient growth medium and medium supplemented with a synthetic iron chelator, 2,2'-dipyridyl, to mimic iron starvation in Foc Tropical Race 4 (Foc TR4). Concentration of extracellular siderophores increased three-fold (p < 0.05) in the absence of iron. Liquid chromatography-mass spectrometry analysis detected the hydroxamate siderophore, ferrichrome, only in the mycelia of iron-starved cultures. Moreover, iron-starved cultures exhibited a reduction in total cellular protein concentration. In contrast, out of the 20 proteinogenic amino acids, only arginine increased (p < 0.05) under iron starvation. Our findings suggest that iron starvation does not cause a remodelling of amino acid metabolism in Foc TR4, except for arginine, which is required for biosynthesis of ornithine, the precursor for siderophore biosynthesis. Collectively, our findings suggest that biosynthesis of siderophores, particularly ferrichrome, could be a counteractive mechanism for Foc TR4 to evade iron starvation.

Plant-Derived Catechols Are Substrates of TonB-Dependent Transporters and Sensitize Pseudomonas aeruginosa to Siderophore-Drug Conjugates.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for acute and chronic infections in immunocompromised hosts. This organism is known to compete efficiently against coinfecting microorganisms, due in part to the secretion of antimicrobial molecules and the synthesis of siderophore molecules with high affinity for iron. P. aeruginosa possess a large repertoire of TonB-dependent transporters for the uptake of its own, as well as xenosiderophores released from other bacteria or fungi. Here, we show that P. aeruginosa is also capable of utilizing plant-derived polyphenols as an iron source. We found that exclusively plant-derived phenols containing a catechol group (i.e., chlorogenic acid, caffeic acid, quercetin, luteolin) induce the expression of the TonB-dependent transporters PiuA or PirA. This induction requires the two-component system PirR-PirS. Chlorogenic acid in its Fe(III)-loaded form was actively transported by PiuA and PirA and supported growth under iron-limiting conditions. Coincidentally, PiuA and PirA are also the main TonB transporters for the recently approved siderophore-drug conjugate cefiderocol. Surprisingly, quercetin supplementation increased the susceptibility of P. aeruginosa to siderophore-drug conjugates, due to induction of piuA and pirA expression mediated by the PirR-PirS two-component system. These findings suggest a potential novel therapeutic application for these biologically active dietary polyphenols. IMPORTANCE Iron is an essential element for living organisms. Most bacteria synthesize species-specific iron chelators, called siderophores, able to capture iron from their host or the environment. Pseudomonas aeruginosa, an opportunistic pathogen, produces two endogenous siderophores but is able to acquire iron also via xenosiderophores, produced by other bacteria or fungi, using a set of conserved TonB transporters. Here, we show that P. aeruginosa is also able to use plant metabolites, like quercetin and chlorogenic acid, as siderophores. These metabolites possess an iron-chelating catechol group and are recognized and transported by the TonB transporters PirA and PiuA. Since these transporters also promote the specific uptake of siderophore-drug conjugates, P. aeruginosa exposed to these plant catechols becomes hypersusceptible to this novel class of antibiotics. This unexpected finding suggests a potential therapeutic application for quercetin and chlorogenic acid, which were mainly investigated for their antioxidant and anti-inflammatory properties.

Iron-Deficiency in Atopic Diseases: Innate Immune Priming by Allergens and Siderophores.

Although iron is one of the most abundant elements on earth, about a third of the world's population are affected by iron deficiency. Main drivers of iron deficiency are beside the chronic lack of dietary iron, a hampered uptake machinery as a result of immune activation. Macrophages are the principal cells distributing iron in the human body with their iron restriction skewing these cells to a more pro-inflammatory state. Consequently, iron deficiency has a pronounced impact on immune cells, favoring Th2-cell survival, immunoglobulin class switching and primes mast cells for degranulation. Iron deficiency during pregnancy increases the risk of atopic diseases in children, while both children and adults with allergy are more likely to have anemia. In contrast, an improved iron status seems to protect against allergy development. Here, the most important interconnections between iron metabolism and allergies, the effect of iron deprivation on distinct immune cell types, as well as the pathophysiology in atopic diseases are summarized. Although the main focus will be humans, we also compare them with innate defense and iron sequestration strategies of microbes, given, particularly, attention to catechol-siderophores. Similarly, the defense and nutritional strategies in plants with their inducible systemic acquired resistance by salicylic acid, which further leads to synthesis of flavonoids as well as pathogenesis-related proteins, will be elaborated as both are very important for understanding the etiology of allergic diseases. Many allergens, such as lipocalins and the pathogenesis-related proteins, are able to bind iron and either deprive or supply iron to immune cells. Thus, a locally induced iron deficiency will result in immune activation and allergic sensitization. However, the same proteins such as the whey protein beta-lactoglobulin can also transport this precious micronutrient to the host immune cells (holoBLG) and hinder their activation, promoting tolerance and protecting against allergy. Since 2019, several clinical trials have also been conducted in allergic subjects using holoBLG as a food for special medical purposes, leading to a reduction in the allergic symptom burden. Supplementation with nutrient-carrying lipocalin proteins can circumvent the mucosal block and nourish selectively immune cells, therefore representing a new dietary and causative approach to compensate for functional iron deficiency in allergy sufferers.

Treatment of carbapenem-resistant Pseudomonas aeruginosa infections: a case for cefiderocol.

INTRODUCTION: Carbapenem-resistant (CR) Pseudomonas aeruginosa infections constitute a serious clinical threat globally. Patients are often critically ill and/or immunocompromised. Antibiotic options are limited and are currently centered on beta-lactam-beta-lactamase inhibitor (BL-BLI) combinations and the siderophore cephalosporin cefiderocol. AREAS COVERED: This article reviews the mechanisms of P. aeruginosa resistance and their potential impact on the activity of current treatment options, along with evidence for the clinical efficacy of BL-BLI combinations in P. aeruginosa infections, some of which specifically target infections due to CR organisms. The preclinical and clinical evidence supporting cefiderocol as a treatment option for P. aeruginosa involving infections is also reviewed. EXPERT OPINION: Cefiderocol is active against most known P. aeruginosa mechanisms mediating carbapenem resistance. It is stable against different serine- and metallo-beta-lactamases, and, due to its iron channel-dependent uptake mechanism, is not impacted by porin channel loss. Furthermore, the periplasmic level of cefiderocol is not affected by upregulated efflux pumps. The potential for on-treatment resistance development currently appears to be low, although more clinical data are required. Information from surveillance programs, real-world compassionate use, and clinical studies demonstrate that cefiderocol is an important treatment option for CR P. aeruginosa infections.

Enforced specialization fosters mutual cheating and not division of labour in the bacterium Pseudomonas aeruginosa.

A common way for bacteria to cooperate is via the secretion of beneficial public goods (proteases, siderophores, biosurfactants) that can be shared amongst individuals in a group. Bacteria often simultaneously deploy multiple public goods with complementary functions. This raises the question whether natural selection could favour division of labour where subpopulations or species specialize in the production of a single public good, whilst sharing the complementary goods at the group level. Here we use an experimental system, where we mix engineered specialists of the bacterium Pseudomonas aeruginosa that can each only produce one of the two siderophores, pyochelin or pyoverdine and explore the conditions under which specialization can lead to division of labour. When growing pyochelin and pyoverdine specialists at different mixing ratios under different levels of iron limitation, we found that specialists could only successfully complement each other in environments with moderate iron limitation and grow as good as the generalist wildtype but not better. Under more stringent iron limitation, the dynamics in specialist communities was characterized by mutual cheating and with higher proportions of pyochelin producers greatly compromising group productivity. Nonetheless, specialist communities remained stable through negative frequency-dependent selection. Our work shows that specialization in a bacterial community can be spurred by cheating and does not necessarily result in beneficial division of labour. We propose that natural selection might favour fine-tuned regulatory mechanisms in generalists over division of labour because the former enables generalists to remain flexible and adequately adjust public good investments in fluctuating environments.

Relationship between iron bioavailability and Salmonella Typhimurium fitness in raw and pasteurized liquid whole egg.

SALMONELLA: Enteritidis growth rates in liquid whole egg have been shown to be dependent on the initial inoculum dose and on the egg product's thermal history. This study's objective is to obtain further insight into the mechanisms underlying both phenomena. First we verified that Salmonella Typhimurium ATCC 14028s cells displayed the behavior already described for S. Enteritidis cells. Then, we carried out supplementation assays by adding different concentrations of egg-white antimicrobial proteins, iron, or siderophores to the egg samples (raw or pasteurized liquid whole egg, depending on the assay). These experiments revealed that addition of lysozyme (at the concentration at which it is present in liquid whole egg) did not affect Salmonella growth in pasteurized liquid whole egg, but that ovotransferrin as well as Ex-FABP caused a significant (p < 0.05) reduction in Salmonella growth rates in whole egg pasteurized at 70 °C for 1.5 min. Furthermore, we observed that the inactivation of ovotransferrin was dependent on treatment intensity within the range studied. On the other hand, addition of iron or siderophores to raw or low temperature (60 °C/3.5 min) pasteurized liquid whole egg increased the growth rate of Salmonella cells inoculated at a low initial dose. The concentration of these supplements required to reach the growth rate of cells inoculated at a high dose was lower for pasteurized than for raw egg. Finally, growth of a set of deletion mutants in genes coding for proteins related to different iron uptake systems, along with supplementation assays using spent medium revealed the key role of salmochelin in growth of S. Typhimurium in raw whole egg. In summary, our results strongly suggest that iron bioavailability determines the fitness (growth rates) of Salmonella cells in liquid whole egg. Thus, the higher the intensity of the thermal treatment applied to liquid egg, the more iron would be available, a phenomenon that would be linked to the denaturation of iron and/or siderophore binding egg proteins. Further work is still required to fully elucidate why lower Salmonella initial doses lead to lower growth rates, but it can be hypothesized that this might be related to a lower amount of siderophores being released to the medium (especially salmochelin), which would also limit iron bioavailability.

Characterization of plant growth-promoting traits of Enterobacter sp. and its ability to promote cadmium/lead accumulation in Centella asiatica L.

In the present study, we characterized the plant growth-promoting traits of Enterobacter sp. FM-1 (FM-1) and investigated its ability to promote growth and increase IAA, P, and Fe concentrations as well as Cd and Pb accumulation in Centella asiatica L. (C. asiatica L.) in upstream area (UA) soil and downstream area (DA) soil that we collected from Siding mine. The results demonstrated that FM-1 secreted IAA, produced siderophores, and had P-solubilization ability even under Cd exposure. IAA secretion reached a maximum of 108.3 ± 1.3 mg L-1 under Cd exposure at 25 mg L-1. Siderophore production reached a maximum of 0.94 ± 0.01 under Cd exposure at 50 mg L-1. Pot experiments indicated that FM-1 successfully colonized the roots of C. asiatica L. In both soils, inoculation with FM-1 decreased the pH in rhizosphere soil and increased the bioavailability of both Cd and Pb. In addition, inoculation with FM-1 increased the IAA, P, and Fe concentrations and simultaneously promoted both Cd and Pb accumulation in C. asiatica L. The Cd and Pb concentrations in leaves increased 1.73- and 1.07-fold in the UA soil and 1.25- and 1.11-fold in the DA soil, respectively. Thus, the Cd-resistant strain FM-1 presented excellent PGP traits and could facilitate Cd and Pb phytoremediation by C. asiatica L.

Hydroxypyridinones as a Very Promising Platform for Targeted Diagnostic and Therapeutic Radiopharmaceuticals.

Hydroxypyridinones (HOPOs) have been used in the chelation therapy of iron and actinide metals. Their application in metal-based radiopharmaceuticals has also been increasing in recent years. This review article focuses on how multidentate HOPOs can be used in targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals. The general structure of radiometal-based targeted radiopharmaceuticals, a brief description of siderophores, the basic structure and properties of bidentate HOPO, some representative HOPO multidentate chelating agents, radiopharmaceuticals based on HOPO multidentate bifunctional chelators for gallium-68, thorium-227 and zirconium-89, as well as the future prospects of HOPO multidentate bifunctional chelators in other metal-based radiopharmaceuticals are described and discussed in turn. The HOPO metal-based radiopharmaceuticals that have shown good prospects in clinical and preclinical studies are gallium-68, thorium-227 and zirconium-89 radiopharmaceuticals. We expect HOPO multidentate bifunctional chelators to be a very promising platform for building novel targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals.

Can Targeting Iron Help in Combating Chronic Pseudomonas Infection? A Systematic 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.