Aims: Endophytic bacteria (EB) living inside plant tissues possess different beneficial traits including siderophore production and other plant growth-promoting (PGP) activities. Siderophore-producing EB promote host plant growth by secreting ferrum in iron-deficient conditions. This study screened 19 siderophore producers in vitro, isolated from upland rice roots grown in mountain farms of Tung Village, Nậm Có Commune, Mù Cang Chải District, Yên Bái Province, Vietnam, for PGP traits, including phosphate solubilisation, indole-3-acetic acid (IAA), ammonia, gelatinase, amylase and catalase production. Methodology and results: The bacteria were identified by Matrix assisted Laser Desorption Ionization Time of Flight mass spectrometry (MALDI-TOF MS). All 19 isolates were identified as genera Pseudomonas, Enterobacter, Pantoe, Bacillus, Burkholderia, Staphylococcus, Ralstonia and Cronotacter. The isolates produced catalase and ammonia. The amount of ammonia ranged from 60.74 ± 0.14 to 466.72 ± 0.18 mg/L. Out of the 19 siderophore producers, 17 (89.47%) were able to solubilise phosphate with solubilisation index (PSI) ranging from 1.12 ± 0.07 to 2.14 ± 0.15. The qualitative assays identified 12 isolates (63.15%) positive for IAA production with a tryptophan concentration of 5 mM, whereas 15 (78.94%) and 17 (89.47%) isolates were positive for gelatin and starch hydrolysis, respectively. Especially, 7 isolates were found to be positive for all tested assays in vitro including Pseudomonas rhodesiae (NC2), Enterobacter asburiae (NC50), Pantoea ananatis (NC63), Bacillus cereus (NC64), Burkholderia cenocepacia (NC110), Staphylococcus sciuri (NC112) and Ralstonia pickettii (NC122). Conclusion, significance and impact of study This study serves as crucial findings of multi-trait plant growth-promoting endophytic bacteria isolated from upland rice root in north-western Vietnam. The seven potential isolates positive for all tested assays could be effective PGP bacteria for bio-inoculants.
Oryza--microbiology ; Siderophores ; Plant Growth Regulators ; Vietnam

Staphylococcus aureus is able to utilize efficiently transferrin-bound iron as an iron source, whereas other staphylococci are not. The reason for this difference remains unclear. We compared the activity of siderophore-mediated iron-uptake systems among S. aureus, S. epidermidis, and S. saprophyticus. S. aureus was more susceptible to streptonigrin than the other two staphylococci. S. aureus was able to utilize efficiently transferrin-bound iron in proportion to the level of iron-saturation and produced siderophores in an inverse relation to iron-saturation. In contrast to S. aureus, S. epidermidis and S. saprophyticus were able to utilize only holotransferrin (HT; about 80% iron- saturated) and produced siderophores only in media containing HT. Moreover, they utilized HT less efficiently than S. aureus, though they produced greater amount of siderophores than S. aureus in media containing HT. The ability of the equivalent siderophores per se to capture iron from HT was not significantly different among the three species. Nevertheless, the siderophores from S. aureus stimulated the growth of the staphylococci to a greater degree than did the siderophores from S. epidermidis and S. saprophyticus. The siderophores from S. epidermidis and S. saprophyticus also stimulated the growth of S. aureus to a greater degree than those of the original bacteria which produced them. This indicates that S. aureus possesses a greater ability to produce more-efficient siderophores responding to very low iron-availability, as well as a greater ability to utilize iron-siderophore complexes, than the other two staphylococci. This explains in part the higher virulence of S. aureus compared to other staphylococci.
Bacteria ; Iron* ; Siderophores ; Staphylococcus aureus ; Streptonigrin ; Transferrin ; Virulence

Background and Objectives: Iron is an essential element that plays a vital role in a wide variety of cellular processes. But when present in excess concentration in organs, it may increase the risk for liver disease, heart failure, and diabetes. Recently, siderophores, which are iron-chelating agents produced by microorganisms, have attracted tremendous attention because of their strong binding and high selectivity to the ferric form of iron. Thus, the use of siderophore in sequestering excess iron in the body as a form of therapy is very attractive. This study determined the effects of commercially available siderophore in sequestering excess iron in organs such as liver, heart, and pancreas under excess iron conditions. Methodology: First, iron-overload was induced by injecting iron dextran (20 mg) into male ICR mice for three consecutive days. The effects of iron to the liver, heart, and pancreas and the possible sequestration by siderophore were determined by scoring histological sections. The liver iron concentration was also assessed by atomic absorption spectroscopy (AAS). Results and Conclusion The study showed that iron-overloaded mice exhibited skin hyperpigmentation and hemosiderosis in liver, heart, and pancreas. Significant changes in the liver include hepatomegaly and development of tumor. Iron-overloaded mice had 2,935% increase in liver iron content compared to the salinetreated mice. However, when iron-overloaded mice were treated with either 100 µg or 200 µg siderophore, there was a 77% and 84% decrease in liver iron content, respectively. Moreover, the treatment of ironoverloaded mice with siderophore prevented the development of hemosiderosis, tumor, and structural changes in the tissues studied. The results showed that siderophore can effectively reduce excess iron and organ damage in iron-overloaded mice and can be potentially employed in chelation therapy of iron-overload diseases. Further studies on the possible mechanisms of siderophore aside from decreasing iron excess and lowering organ dysfunction are recommended.
Siderophores ; Iron Overload ; Iron Chelating Agents ; Hemosiderosis ; Hepatomegaly

Pathogenic bacteria survive in iron-limited host environments by using several iron acquisition mechanisms. Acinetobacter baumannii, causing serious infections in compromised patients, produces an iron-chelating molecule, called acinetobactin, which is composed of equimolar quantities of 2,3-dihydroxybenzoic acid (DHBA), L-threonine, and N-hydroxyhistamine, to compete with host cells for iron. Genes that are involved in the production and transport of acinetobactin are clustered within the genome of A. baumannii. A recent study showed that entA, located outside of the acinetobactin gene cluster, plays important roles in the biosynthesis of the acinetobactin precursor DHBA and in bacterial pathogenesis. Therefore, understanding the genes that are associated with the biosynthesis and transport of acinetobactin in the bacterial genome is required. This review is intended to provide a general overview of the genes in the genome of A. baumannii that are required for acinetobactin biosynthesis and transport.
Acinetobacter baumannii* ; Bacteria ; Genome ; Genome, Bacterial ; Humans ; Iron ; Multigene Family ; Siderophores ; Threonine

To elucidate iron utilization patterns of Staphylococcus aureus according to the growth, we checked the residual iron concentration and the production of siderophores at the indicated times while culturing S. aureus ATCC 6538 and 25923 strains in brain heart infusion broth. By using streptonigrin susceptibility test and investigating growth curves in three culture media of which iron concentration is 0.2, 20, 45 uM, respectively, we found out that iron metabolism of 6538 strain was more active than that of 25923 strain. In point of tendency of iron consumption, 6538 strain steeply consumed iron just before the onset of stationary phase, but 25923 strain did gradually iron throughout the growth phase. Nevertheless, total amount of iron consumed by each strain during the growth was almost no difference between the strains. CAS diffusion assay in detecting siderophores showed that siderophore production followed iron consumption. These results suggest that the siderophores play significant role in iron utilization in vitro.
Brain ; Culture Media ; Diffusion ; Heart ; Iron* ; Metabolism ; Siderophores ; Staphylococcus aureus* ; Staphylococcus* ; Streptonigrin

BACKGROUND: Staphylococcus epidermidis is the most common pathogen of chronic ambulatory peritoneal dialysis peritonitis. It has been believed that the activity of iron-uptake system (IUS) may play an important role in the growth of S. epidermidis in human peritoneal dialysate (HPD) solution, but there is no report using mutants with defective IUS. A streptonigrin-resistant S. epidermidis (SRSE) strain was isolated from S. epidermidis KCTC 1917 and functionally characterized. MATERIALS AND METHODS: Bacterial growth was monitored by measuring the optical densities of culture fluids obtained at appropriate intervals at a wavelength of 600 nm. CAS agar diffusion assay was used for the comparison of siderophore production, 6 M urea-gel electrophoresis for the comparison of the ability to capture iron from transferrin, and bioassay for the observation of the ability to utilize iron-siderophore complexes. RESULTS: The SRSE strain ineffectively utilized transferrin-bound iron for growth despite its ability to produce considerably larger amount of siderophores than its parental strain. The growth of the parental strain, but not the SRSE strain, was stimulated on transferrin-bound iron by its own siderophores each. The growth of the SRSE strain in the HPD solution was retarded compared to that of the parental strain. CONCLUSION: These results indicate that the SRSE strain is defective in its ability to utilize the iron-siderophore complexes, rather than its ability to produce siderophores, and that the siderophore-mediated IUS plays an important role in the growth of S. epidermidis in HPD solution.
Agar ; Biological Assay ; Diffusion ; Electrophoresis ; Humans* ; Iron ; Parents ; Peritoneal Dialysis ; Peritonitis ; Siderophores ; Staphylococcus epidermidis* ; Staphylococcus* ; Transferrin

BACKGROUND: Staphylococcus epidermidis is the most common pathogen of chronic ambulatory peritoneal dialysis peritonitis. It has been believed that the activity of iron-uptake system (IUS) may play an important role in the growth of S. epidermidis in human peritoneal dialysate (HPD) solution, but there is no report using mutants with defective IUS. A streptonigrin-resistant S. epidermidis (SRSE) strain was isolated from S. epidermidis KCTC 1917 and functionally characterized. MATERIALS AND METHODS: Bacterial growth was monitored by measuring the optical densities of culture fluids obtained at appropriate intervals at a wavelength of 600 nm. CAS agar diffusion assay was used for the comparison of siderophore production, 6 M urea-gel electrophoresis for the comparison of the ability to capture iron from transferrin, and bioassay for the observation of the ability to utilize iron-siderophore complexes. RESULTS: The SRSE strain ineffectively utilized transferrin-bound iron for growth despite its ability to produce considerably larger amount of siderophores than its parental strain. The growth of the parental strain, but not the SRSE strain, was stimulated on transferrin-bound iron by its own siderophores each. The growth of the SRSE strain in the HPD solution was retarded compared to that of the parental strain. CONCLUSION: These results indicate that the SRSE strain is defective in its ability to utilize the iron-siderophore complexes, rather than its ability to produce siderophores, and that the siderophore-mediated IUS plays an important role in the growth of S. epidermidis in HPD solution.
Agar ; Biological Assay ; Diffusion ; Electrophoresis ; Humans* ; Iron ; Parents ; Peritoneal Dialysis ; Peritonitis ; Siderophores ; Staphylococcus epidermidis* ; Staphylococcus* ; Transferrin

Antimicrobial resistance is one of the critical public health issues in the world. There is an urgent need to develop effective broad-spectrum antibiotics to treat the infection of multi-drug resistant Gram-negative bacilli. Cefiderocol, developed by the Shionogi Inc. in Japan, is a new type of iron carrier cephalosporin antibiotics, which overcomes the drug resistance of Gram-negative bacilli due to the down-regulation of outer membrane pore protein and the up-regulation of efflux pump, and has good stability to serine- and metallo-carbapenemases. This drug has a broad spectrum and strong antibacterial activity against carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Cefiderocol can be used to treat complex urinary tract infections (including pyelonephritis), hospital-acquired pneumonia, and ventilator-associated pneumonia. By summarizing the chemical structure, antibacterial mechanism, in vitro antibacterial activity, pharmacokinetics, pharmacodynamics, and clinical treatment of cefiderocol, this review shows the application potential of cefiderocol as a new iron carrier cephalosporin in the treatment of multi-drug resistant Gram-negative bacilli infections.
Cephalosporins/therapeutic use* ; Gram-Negative Bacteria ; Microbial Sensitivity Tests ; Siderophores/pharmacology*

Iron is an essential trace element for both humans and bacteria. It plays a vital role in life, such as in redox reactions and electron transport. Strict regulatory mechanisms are necessary to maintain iron homeostasis because both excess and insufficient iron are harmful to life. Competition for iron is a war between humans and bacteria. To grow, reproduce, colonize, and successfully cause infection, pathogens have evolved various mechanisms for iron uptake from humans, principally Fe 3+ -siderophore and Fe 2+ -heme transport systems. Humans have many innate immune mechanisms that regulate the distribution of iron and inhibit bacterial iron uptake to help resist bacterial invasion and colonization. Meanwhile, researchers have invented detection test strips and coupled antibiotics with siderophores to create tools that take advantage of this battle for iron, to help eliminate pathogens. In this review, we summarize bacterial and human iron metabolism, competition for iron between humans and bacteria, siderophore sensors, antibiotics coupled with siderophores, and related phenomena. We also discuss how competition for iron can be used for diagnosis and treatment of infection in the future.
Humans ; Siderophores/metabolism* ; Iron/metabolism* ; Bacteria ; Anti-Bacterial Agents/pharmacology* ; Biological Transport

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters