# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 581 | 0 | 0.9951 | Inorganic polyphosphates and heavy metal resistance in microorganisms. The mechanisms of heavy metal resistance in microbial cells involve multiple pathways. They include the formation of complexes with specific proteins and other compounds, the excretion from the cells via plasma membrane transporters in case of procaryotes, and the compartmentalization of toxic ions in vacuoles, cell wall and other organelles in case of eukaryotes. The relationship between heavy metal tolerance and inorganic polyphosphate metabolism was demonstrated both in prokaryotic and eukaryotic microorganisms. Polyphosphates, being polyanions, are involved in detoxification of heavy metals through complex formation and compartmentalization. The bacteria and fungi cultivated in the presence of some heavy metal cations contain the enhanced levels of polyphosphate. In bacteria, polyphosphate sequesters heavy metals; some of metal cations stimulate an exopolyphosphatase activity, which releases phosphate from polyphosphates, and MeHPO(4)(-) ions are then transported out of the cells. In fungi, the overcoming of heavy metal stresses is associated with the accumulation of polyphosphates in cytoplasmic inclusions, vacuoles and cell wall and the formation of cation/polyphosphate complexes. The effects of knockout mutations and overexpression of the genes encoding polyphosphate-metabolizing enzymes on heavy metal resistance are discussed. | 2018 | 30151754 |
| 580 | 1 | 0.9950 | Acid-tolerant bacteria and prospects in industrial and environmental applications. Acid-tolerant bacteria such as Streptococcus mutans, Acidobacterium capsulatum, Escherichia coli, and Propionibacterium acidipropionici have developed several survival mechanisms to sustain themselves in various acid stress conditions. Some bacteria survive by minor changes in the environmental pH. In contrast, few others adapt different acid tolerance mechanisms, including amino acid decarboxylase acid resistance systems, mainly glutamate-dependent acid resistance (GDAR) and arginine-dependent acid resistance (ADAR) systems. The cellular mechanisms of acid tolerance include cell membrane alteration in Acidithiobacillus thioxidans, proton elimination by F(1)-F(0)-ATPase in Streptococcus pyogenes, biofilm formation in Pseudomonas aeruginosa, cytoplasmic urease activity in Streptococcus mutans, synthesis of the protective cloud of ammonia, and protection or repair of macromolecules in Bacillus caldontenax. Apart from cellular mechanisms, there are several acid-tolerant genes such as gadA, gadB, adiA, adiC, cadA, cadB, cadC, speF, and potE that help the bacteria to tolerate the acidic environment. This acid tolerance behavior provides new and broad prospects for different industrial applications and the bioremediation of environmental pollutants. The development of engineered strains with acid-tolerant genes may improve the efficiency of the transgenic bacteria in the treatment of acidic industrial effluents. KEY POINTS: • Bacteria tolerate the acidic stress by methylating unsaturated phospholipid tail • The activity of decarboxylase systems for acid tolerance depends on pH • Genetic manipulation of acid-tolerant genes improves acid tolerance by the bacteria. | 2023 | 37093306 |
| 653 | 2 | 0.9950 | Connecting Algal Polysaccharide Degradation to Formaldehyde Detoxification. Formaldehyde is a toxic metabolite that is formed in large quantities during bacterial utilization of the methoxy sugar 6-O-methyl-d-galactose, an abundant monosaccharide in the red algal polysaccharide porphyran. Marine bacteria capable of metabolizing porphyran must therefore possess suitable detoxification systems for formaldehyde. We demonstrate here that detoxification of formaldehyde in the marine Flavobacterium Zobellia galactanivorans proceeds via the ribulose monophosphate pathway. Simultaneously, we show that the genes encoding the key enzymes of this pathway are important for maintaining high formaldehyde resistance. Additionally, these genes are upregulated in the presence of porphyran, allowing us to connect porphyran degradation to the detoxification of formed formaldehyde. | 2022 | 35561127 |
| 585 | 3 | 0.9948 | Genetic susceptibility to intracellular infections: Nramp1, macrophage function and divalent cations transport. Nramp1 is one of the few host resistance genes that have been characterized at the molecular level. Nramp1 is an integral membrane protein expressed in the lysosomal compartment of macrophages and is recruited to the membrane of bacterial phagosomes where it affects intracellular microbial replication. Nramp1 is part of a very large gene family conserved from bacteria and man that codes for transporters of divalent cations transporters. We propose that Nramp1 affects the intraphagosomal microbial replication by modulating divalent cations content in this organelle. Both mammalian and bacterial transporters may compete for the same substrate in the phagosomal space. | 2000 | 10679418 |
| 124 | 4 | 0.9948 | A bacterial view of the periodic table: genes and proteins for toxic inorganic ions. Essentially all bacteria have genes for toxic metal ion resistances and these include those for Ag+, AsO2-, AsO4(3-), Cd2+ Co2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, TeO3(2-), Tl+ and Zn2+. The largest group of resistance systems functions by energy-dependent efflux of toxic ions. Fewer involve enzymatic transformations (oxidation, reduction, methylation, and demethylation) or metal-binding proteins (for example, metallothionein SmtA, chaperone CopZ and periplasmic silver binding protein SilE). Some of the efflux resistance systems are ATPases and others are chemiosmotic ion/proton exchangers. For example, Cd2+-efflux pumps of bacteria are either inner membrane P-type ATPases or three polypeptide RND chemiosmotic complexes consisting of an inner membrane pump, a periplasmic-bridging protein and an outer membrane channel. In addition to the best studied three-polypeptide chemiosmotic system, Czc (Cd2+, Zn2+, and Co2), others are known that efflux Ag+, Cu+, Ni2+, and Zn2+. Resistance to inorganic mercury, Hg2+ (and to organomercurials, such as CH3Hg+ and phenylmercury) involve a series of metal-binding and membrane transport proteins as well as the enzymes mercuric reductase and organomercurial lyase, which overall convert more toxic to less toxic forms. Arsenic resistance and metabolizing systems occur in three patterns, the widely-found ars operon that is present in most bacterial genomes and many plasmids, the more recently recognized arr genes for the periplasmic arsenate reductase that functions in anaerobic respiration as a terminal electron acceptor, and the aso genes for the periplasmic arsenite oxidase that functions as an initial electron donor in aerobic resistance to arsenite. | 2005 | 16133099 |
| 8532 | 5 | 0.9948 | Simultaneous volatile fatty acids promotion and antibiotic resistance genes reduction in fluoranthene-induced sludge alkaline fermentation: Regulation of microbial consortia and cell functions. The impact and mechanism of fluoranthene (Flr), a typical polycyclic aromatic hydrocarbon highly detected in sludge, on alkaline fermentation for volatile fatty acids (VFAs) recovery and antibiotic resistance genes (ARGs) transfer were studied. The results demonstrated that VFAs production increased from 2189 to 4272 mg COD/L with a simultaneous reduction of ARGs with Flr. The hydrolytic enzymes and genes related to glucose and amino acid metabolism were provoked. Also, Flr benefited for the enrichment of hydrolytic-acidifying consortia (i.e., Parabacteroides and Alkalibaculum) while reduced VFAs consumers (i.e., Rubrivivax) and ARGs potential hosts (i.e., Rubrivivax and Pseudomonas). Metagenomic analysis indicated that the genes related to cell wall synthesis, biofilm formation and substrate transporters to maintain high VFAs-producer activities were upregulated. Moreover, cell functions of efflux pump and Type IV secretion system were suppressed to inhibit ARGs proliferation. This study provided intrinsic mechanisms of Flr-induced VFAs promotion and ARGs reduction during alkaline fermentation. | 2024 | 38266788 |
| 8543 | 6 | 0.9948 | Soil bacteria, genes, and metabolites stimulated during sulfur cycling and cadmium mobilization under sodium sulfate stress. Sodium sulfate stress is known to improve cadmium (Cd) mobilization in soil and microbial sulfur oxidation, Cd resistance, and the accumulation of stress tolerance-associated metabolites has been correlated with increased soil Cd availability and toxicity. In this study, aerobic soil microcosms with Cd-contamination were stimulated with sodium sulfate to investigate its effects on soil microbial community structure, functional genes, and associated metabolite profiles. Metagenomic analysis revealed that sulfur oxidizing and Cd-resistant bacteria carried gene clusters encoding sox, dsr, and sqr genes, and znt, czc, and cad genes, respectively. Exposure to sodium sulfate resulted in the reprogram of soil metabolites. In particular, intensification of sulfur metabolism triggered an up-regulation in the tricarboxylic acid (TCA) cycle, which promoted the secretion of carboxylic acids and their precursors by soil bacteria. The accumulation of organic acids induced in response to high sodium sulfate dosages potentially drove an observed increase in Cd mobility. Pseudomonas and Erythrobacter spp. exhibited a high capacity for adaptation to heavy metal- or sulfur-induced stress, evident by an increased abundance of genes and metabolites for sulfur cycling and Cd resistance. These results provide valuable insights towards understanding the microbial mechanisms of sulfur transformation and Cd dissolution under saline stress. | 2021 | 34214562 |
| 579 | 7 | 0.9946 | Control of expression of a periplasmic nickel efflux pump by periplasmic nickel concentrations. There is accumulating evidence that transenvelope efflux pumps of the resistance, nodulation, cell division protein family (RND) are excreting toxic substances from the periplasm across the outer membrane directly to the outside. This would mean that resistance of Gram-negative bacteria to organic toxins and heavy metals is in fact a two-step process: one set of resistance factors control the concentration of a toxic substance in the periplasm, another one that in the cytoplasm. Efficient periplasmic detoxification requires periplasmic toxin sensing and transduction of this signal into the cytoplasm to control expression of the periplasmic detoxification system. Such a signal transduction system was analyzed using the Cnr nickel resistance system from Cupriavidus (Wautersia, Ralstonia, Alcaligenes) metallidurans strain CH34. Resistance is based on nickel efflux mediated by the CnrCBA efflux pump encoded by the cnrYHXCBAT metal resistance determinant. The products of the three genes cnrYXH transcriptionally regulate expression of cnr. CnrY and CnrX are membrane-bound proteins probably functioning as anti sigma factors while CnrH is a cnr-specific extracytoplasmic functions (ECF) sigma factors. Experimental data provided here indicate a signal transduction chain leading from nickel in the periplasm to transcription initiation at the cnr promoters cnrYp and cnrCp, which control synthesis of the nickel efflux pump CnrCBA. | 2005 | 16158236 |
| 584 | 8 | 0.9945 | Cadmium and iron transport by members of a plant metal transporter family in Arabidopsis with homology to Nramp genes. Metal cation homeostasis is essential for plant nutrition and resistance to toxic heavy metals. Many plant metal transporters remain to be identified at the molecular level. In the present study, we have isolated AtNramp cDNAs from Arabidopsis and show that these genes complement the phenotype of a metal uptake deficient yeast strain, smf1. AtNramps show homology to the Nramp gene family in bacteria, yeast, plants, and animals. Expression of AtNramp cDNAs increases Cd(2+) sensitivity and Cd(2+) accumulation in yeast. Furthermore, AtNramp3 and AtNramp4 complement an iron uptake mutant in yeast. This suggests possible roles in iron transport in plants and reveals heterogeneity in the functional properties of Nramp transporters. In Arabidopsis, AtNramps are expressed in both roots and aerial parts under metal replete conditions. Interestingly, AtNramp3 and AtNramp4 are induced by iron starvation. Disruption of the AtNramp3 gene leads to slightly enhanced cadmium resistance of root growth. Furthermore, overexpression of AtNramp3 results in cadmium hypersensitivity of Arabidopsis root growth and increased accumulation of Fe, on Cd(2+) treatment. Our results show that Nramp genes in plants encode metal transporters and that AtNramps transport both the metal nutrient Fe and the toxic metal cadmium. | 2000 | 10781110 |
| 600 | 9 | 0.9945 | Protein aggregation caused by aminoglycoside action is prevented by a hydrogen peroxide scavenger. Protein mistranslation causes growth arrest in bacteria, mitochondrial dysfunction in yeast, and neurodegeneration in mammals. It remains poorly understood how mistranslated proteins cause such cellular defects. Here we demonstrate that streptomycin, a bactericidal aminoglycoside that increases ribosomal mistranslation, induces transient protein aggregation in wild-type Escherichia coli. We further determined the aggregated proteome using label-free quantitative mass spectrometry. To identify genes that reduce cellular mistranslation toxicity, we selected from an overexpression library protein products that increased resistance against streptomycin and kanamycin. The selected proteins were significantly enriched in members of the oxidation-reduction pathway. Overexpressing one of these proteins, alkyl hydroperoxide reductase subunit F (a protein defending bacteria against hydrogen peroxide), but not its inactive mutant suppressed aggregated protein formation upon streptomycin treatment and increased aminoglycoside resistance. This work provides in-depth analyses of an aggregated proteome caused by streptomycin and suggests that cellular defense against hydrogen peroxide lowers the toxicity of mistranslation. | 2012 | 23122414 |
| 138 | 10 | 0.9945 | Resistance mechanisms to arsenicals and antimonials. Salts and organic derivatives of arsenic and antimony are quite toxic. Living organisms have adapted to this toxicity by the evolution of resistance mechanisms. Both prokaryotic and eukaryotic cells develop resistance when exposed to arsenicals or antimonials. In the case of bacteria resistance is conferred by plasmid-encoded arsenical resistance (ars) operons. The genes and gene products of the ars operon of the clinically-isolated conjugative R-factor R773 have been identified and their mechanism of action elucidated. The operon encodes an ATP-driven pump that extrudes arsenite and antimonite from the cells. The lowering of their intracellular concentration results in resistance. Arsenate resistance results from the action of the plasmid-encoded arsenate reductase that reduces arsenate to arsenite, which is then pumped out of the cell. | 1995 | 8852270 |
| 778 | 11 | 0.9945 | Identification and molecular characterization of an efflux pump involved in Pseudomonas putida S12 solvent tolerance. Bacteria able to grow in aqueous:organic two-phase systems have evolved resistance mechanisms to the toxic effects of solvents. One such mechanism is the active efflux of solvents from the cell, preserving the integrity of the cell interior. Pseudomonas putida S12 is resistant to a wide variety of normally detrimental solvents due to the action of such an efflux pump. The genes for this solvent efflux pump were cloned from P. putida S12 and their nucleotide sequence determined. The deduced amino acid sequences encoded by the three genes involved show a striking resemblance to proteins known to be involved in proton-dependent multidrug efflux systems. Transfer of the genes for the solvent efflux pump to solvent-sensitive P. putida strains results in the acquisition of solvent resistance. This opens up the possibilities of using the solvent efflux system to construct bacterial strains capable of performing biocatalytic transformations of insoluble substrates in two-phase aqueous:organic medium. | 1998 | 9417051 |
| 8195 | 12 | 0.9945 | Comparative proteomics reveals essential mechanisms for osmotolerance in Gluconacetobacter diazotrophicus. Plant growth-promoting bacteria are a promising alternative to improve agricultural sustainability. Gluconacetobacter diazotrophicus is an osmotolerant bacterium able to colonize several plant species, including sugarcane, coffee, and rice. Despite its biotechnological potential, the mechanisms controlling such osmotolerance remain unclear. The present study investigated the key mechanisms of resistance to osmotic stress in G. diazotrophicus. The molecular pathways regulated by the stress were investigated by comparative proteomics, and proteins essential for resistance were identified by knock-out mutagenesis. Proteomics analysis led to identify regulatory pathways for osmotic adjustment, de novo saturated fatty acids biosynthesis, and uptake of nutrients. The mutagenesis analysis showed that the lack of AccC protein, an essential component of de novo fatty acid biosynthesis, severely affected G. diazotrophicus resistance to osmotic stress. Additionally, knock-out mutants for nutrients uptake (Δtbdr and ΔoprB) and compatible solutes synthesis (ΔmtlK and ΔotsA) became more sensitive to osmotic stress. Together, our results identified specific genes and mechanisms regulated by osmotic stress in an osmotolerant bacterium, shedding light on the essential role of cell envelope and extracytoplasmic proteins for osmotolerance. | 2021 | 33035671 |
| 137 | 13 | 0.9945 | Bacterial transformations of and resistances to heavy metals. Bacteria carry out chemical transformations of heavy metals. These transformations (including oxidation, reduction, methylation, and demethylation) are sometimes byproducts of normal metabolism and confer no known advantage upon the organism responsible. Sometimes, however, the transformations constitute a mechanism of resistance. Many species of bacteria have genes that control resistances to specific toxic heavy metals. These resistances often are determined by extrachromosomal DNA molecules (plasmids). The same mechanisms of resistance occur in bacteria from soil, water, industrial waste, and clinical sources. The mechanism of mercury and organomercurial resistance is the enzymatic detoxification of the mercurials into volatile species (methane, ethane, metallic HgO) which are rapidly lost from the environment. Cadmium and arsenate resistances are due to reduced net accumulation of these toxic materials. Efficient efflux pumps cause the rapid excretion of Cd2+ and AsO4(3-). The mechanisms of arsenite and of antimony resistance, usually found associated with arsenate resistance, are not known. Silver resistance is due to lowered affinity of the cells for Ag+, which can be complexed with extracellular halides, thiols, or organic compounds. Sensitivity is due to binding of Ag+ more effectively to cells than to Cl-. | 1984 | 6367730 |
| 746 | 14 | 0.9944 | Novel antimicrobial 3-phenyl-4-phenoxypyrazole derivatives target cell wall lipid intermediates with low mammalian cytotoxicity. The growing crisis of antimicrobial resistance (AMR) underscores the critical need for innovative antimicrobial discoveries. Novel antibiotics targeting the bacterial cell wall remain an attractive area of research, due to their conservation and essentiality in bacteria and their absence in eukaryotic cells. Antibiotics targeting lipid II are of special interest due to the reduced potential for target modification of lipid components and their surface accessibility to inhibitors. In this study, we identified 3-phenyl-4-phenoxypyrazole analogues named PYO12 and PYO12a with bactericidal activity against gram-positive bacteria and low cytotoxicity for different types of mammalian cells. Gram-negative bacteria were resistant to PYO12 activity through extrusion of this compound via efflux pumps. Exposure to PYO12 induces expression of genes involved in resistance to antimicrobials targeting the cell wall, suggesting that PYO12 acts via binding to lipid II or other lipid intermediates involved in peptidoglycan or teichoic acid biosynthesis. Antagonism of PYO12 antibacterial activity by undecaprenyl-pyrophosphate supports the idea that PYO12 may bind to the lipid moiety of lipid II blocking the shuttling of peptidoglycan precursors across the cytoplasmic membrane. These findings open opportunities to further develop these compounds as antibiotics targeting bacterial cell wall synthesis. | 2025 | 41083642 |
| 8544 | 15 | 0.9944 | Closed fixed-bed bacteria-algae biofilm reactor: A promising solution for phenol containing wastewater treatment and resource transformation. This study focuses on treating phenolic wastewater with a novel closed fixed-bed bacteria-algae biofilm reactor (CF-BABR) to enhance resource transformation for phenolic substances. The CF-BABR showed strong impact - load resistance and stable degradation efficiency, fully degrading phenolic compounds at concentrations from 0 to 150 mg/L. From the inflow to the outflow, the effective sequences, abundance, and diversity of bacteria decreased. Chlorobaculum was the dominant bacterium for phenolic pollutant degradation. The abundance of fungi decreased gradually, while their diversity increased. Kalenjinia and Cutaneotrichosporon played a synergistic role in reducing pollutant toxicity. The high - concentration pollutants at the influent led to a higher abundance of microalgal communities, and Scenedesmaceae became the most dominant algal family, which was positively correlated with the degradation of phenolic compounds. Functional gene prediction indicated that the abundance of functional genes in bacteria decreased overall along the wastewater flow. Carbohydrate metabolism and amino acid metabolism were the most active secondary pathways. In fungi, the predicted gene functions had the highest abundance in the upstream region. Metabolic intermediates such as organic acids and derivatives, lipids and lipid - like molecules, and carboxylic acids and derivatives demonstrated the degradation effect of CF-BABR on phenolic compounds. | 2025 | 40194331 |
| 8269 | 16 | 0.9944 | Molecular genetics of Rhizobium Meliloti symbiotic nitrogen fixation. The application of recombinant DNA techniques to the study of symbiotic nitrogen fixation has yielded a growing list of Rhizobium meliloti genes involved in the processes of nodulation, infection thread formation and nitrogenase activity in nodules on the roots of the host plant, Medicago sativa (alfalfa). Interaction with the plant is initiated by genes encoding sensing and motility systems by which the bacteria recognizes and approaches the root. Signal molecules, such as flavonoids, mediate a complex interplay of bacterial and plant nodulation genes leading to entry of the bacteria through a root hair. As the nodule develops, the bacteria proceed inward towards the cortex within infection threads, the formation of which depends on bacterial genes involved in polysaccharide synthesis. Within the cortex, the bacteria enter host cells and differentiate into forms known as bacteroids. Genes which encode and regulate nitrogenase enzyme are expressed in the mature nodule, together with other genes required for import and metabolism of carbon and energy sources offered by the plant. | 1989 | 14542173 |
| 766 | 17 | 0.9944 | The essential inner membrane protein YejM is a metalloenzyme. Recent recurrent outbreaks of Gram-negative bacteria show the critical need to target essential bacterial mechanisms to fight the increase of antibiotic resistance. Pathogenic Gram-negative bacteria have developed several strategies to protect themselves against the host immune response and antibiotics. One such strategy is to remodel the outer membrane where several genes are involved. yejM was discovered as an essential gene in E. coli and S. typhimurium that plays a critical role in their virulence by changing the outer membrane permeability. How the inner membrane protein YejM with its periplasmic domain changes membrane properties remains unknown. Despite overwhelming structural similarity between the periplasmic domains of two YejM homologues with hydrolases like arylsulfatases, no enzymatic activity has been previously reported for YejM. Our studies reveal an intact active site with bound metal ions in the structure of YejM periplasmic domain. Furthermore, we show that YejM has a phosphatase activity that is dependent on the presence of magnesium ions and is linked to its function of regulating outer membrane properties. Understanding the molecular mechanism by which YejM is involved in outer membrane remodeling will help to identify a new drug target in the fight against the increased antibiotic resistance. | 2020 | 33082366 |
| 8487 | 18 | 0.9943 | Mechanisms of nano zero-valent iron in enhancing dibenzofuran degradation by a Rhodococcus sp.: Trade-offs between ATP production and protection against reactive oxygen species. Nano zero-valent iron (nZVI) can enhance pollutants biodegradation, but it displays toxicity towards microorganisms. Gram-positive (G(+)) bacteria exhibit greater resistance to nZVI than Gram-negative bacteria. However, mechanisms of nZVI accelerating pollutants degradation by G(+) bacteria remain unclear. Herein, we explored effects of nZVI on a G(+) bacterium, Rhodococcus sp. strain p52, and mechanisms by which nZVI accelerates biodegradation of dibenzofuran, a typical polycyclic aromatic compound. Electron microscopy and energy dispersive spectroscopy analysis revealed that nZVI could penetrate cell membranes, which caused damage and growth inhibition. nZVI promoted dibenzofuran biodegradation at certain concentrations, while higher concentration functioned later due to the delayed reactive oxygen species (ROS) mitigation. Transcriptomic analysis revealed that cells adopted response mechanisms to handle the elevated ROS induced by nZVI. ATP production was enhanced by accelerated dibenzofuran degradation, providing energy for protein synthesis related to antioxidant stress and damage repair. Meanwhile, electron transport chain (ETC) was adjusted to mitigate ROS accumulation, which involved downregulating expression of ETC complex I-related genes, as well as upregulating expression of the genes for the ROS-scavenging cytochrome bd complex and ETC complex II. These findings revealed the mechanisms underlying nZVI-enhanced biodegradation by G(+) bacteria, offering insights into optimizing bioremediation strategies involving nZVI. | 2025 | 39549579 |
| 586 | 19 | 0.9943 | Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum. Dictyostelium cells are forest soil amoebae, which feed on bacteria and proliferate as solitary cells until bacteria are consumed. Starvation triggers a change in life style, forcing cells to gather into aggregates to form multicellular organisms capable of cell differentiation and morphogenesis. As a soil amoeba and a phagocyte that grazes on bacteria as the obligate source of food, Dictyostelium could be a natural host of pathogenic bacteria. Indeed, many pathogens that occasionally infect humans are hosted for most of their time in protozoa or free-living amoebae, where evolution of their virulence traits occurs. Due to these features and its amenability to genetic manipulation, Dictyostelium has become a valuable model organism for studying strategies of both the host to resist infection and the pathogen to escape the defense mechanisms. Similarly to higher eukaryotes, iron homeostasis is crucial for Dictyostelium resistance to invasive bacteria. Iron is essential for Dictyostelium, as both iron deficiency or overload inhibit cell growth. The Dictyostelium genome shares with mammals many genes regulating iron homeostasis. Iron transporters of the Nramp (Slc11A) family are represented with two genes, encoding Nramp1 and Nramp2. Like the mammalian ortholog, Nramp1 is recruited to phagosomes and macropinosomes, whereas Nramp2 is a membrane protein of the contractile vacuole network, which regulates osmolarity. Nramp1 and Nramp2 localization in distinct compartments suggests that both proteins synergistically regulate iron homeostasis. Rather than by absorption via membrane transporters, iron is likely gained by degradation of ingested bacteria and efflux via Nramp1 from phagosomes to the cytosol. Nramp gene disruption increases Dictyostelium sensitivity to infection, enhancing intracellular growth of Legionella or Mycobacteria. Generation of mutants in other "iron genes" will help identify genes essential for iron homeostasis and resistance to pathogens. | 2013 | 24066281 |