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Parasitology Jan 2024Leishmaniasis is a vector-borne parasitic disease caused by parasites with a spectrum of clinical manifestations, ranging from skin lesions to severe visceral... (Review)
Review
Leishmaniasis is a vector-borne parasitic disease caused by parasites with a spectrum of clinical manifestations, ranging from skin lesions to severe visceral complications. Treatment of this infection has been extremely challenging with the concurrent emergence of drug resistance. The differential gene expression and the discrepancies in protein functions contribute to the appearance of 2 distinct phenotypes: resistant and sensitive, but the current diagnostic tools fail to differentiate between them. The identification of gene expression patterns and molecular mechanisms coupled with antimony (Sb) resistance can be leveraged to prompt diagnosis and select the most effective treatment methods. The present study attempts to use comparative expression of Sb resistance-associated genes in resistant and sensitive , to disclose their relative abundance in clinical or selected isolates to gain an understanding of the molecular mechanisms of Sb response/resistance. Data suggest that the analysis of resistance gene expression would verify the Sb resistance or susceptibility only to a certain extent; however, none of the individual expression patterns of the studied genes was diagnostic as a biomarker of Sb response of . The findings highlighted will be useful in bridging the knowledge gap and discovering innovative diagnostic tools and novel therapeutic targets.
Topics: Leishmania; Antimony; Proteomics; Antiprotozoal Agents; Drug Resistance; Gene Expression
PubMed: 38012864
DOI: 10.1017/S0031182023001129 -
The ISME Journal Aug 2023Microorganisms play crucial roles in phosphorus (P) turnover and P bioavailability increases in heavy metal-contaminated soils. However, microbially driven P-cycling...
Microorganisms play crucial roles in phosphorus (P) turnover and P bioavailability increases in heavy metal-contaminated soils. However, microbially driven P-cycling processes and mechanisms of their resistance to heavy metal contaminants remain poorly understood. Here, we examined the possible survival strategies of P-cycling microorganisms in horizontal and vertical soil samples from the world's largest antimony (Sb) mining site, which is located in Xikuangshan, China. We found that total soil Sb and pH were the primary factors affecting bacterial community diversity, structure and P-cycling traits. Bacteria with the gcd gene, encoding an enzyme responsible for gluconic acid production, largely correlated with inorganic phosphate (Pi) solubilization and significantly enhanced soil P bioavailability. Among the 106 nearly complete bacterial metagenome-assembled genomes (MAGs) recovered, 60.4% carried the gcd gene. Pi transportation systems encoded by pit or pstSCAB were widely present in gcd-harboring bacteria, and 43.8% of the gcd-harboring bacteria also carried the acr3 gene encoding an Sb efflux pump. Phylogenetic and potential horizontal gene transfer (HGT) analyses of acr3 indicated that Sb efflux could be a dominant resistance mechanism, and two gcd-harboring MAGs appeared to acquire acr3 through HGT. The results indicated that Sb efflux could enhance P cycling and heavy metal resistance in Pi-solubilizing bacteria in mining soils. This study provides novel strategies for managing and remediating heavy metal-contaminated ecosystems.
Topics: Antimony; Soil; Phosphates; Phosphorus; Phylogeny; Environmental Monitoring; Soil Pollutants; Metals, Heavy; Bacteria; Microbiota; China; Soil Microbiology
PubMed: 37270585
DOI: 10.1038/s41396-023-01445-6 -
Frontiers in Cellular and Infection... 2022The central theme of this enterprise is to find common features, if any, displayed by genetically different antimony (Sb)-resistant viscerotropic parasites to impart Sb...
The central theme of this enterprise is to find common features, if any, displayed by genetically different antimony (Sb)-resistant viscerotropic parasites to impart Sb resistance. In a limited number of clinical isolates ( = 3), we studied the breadth of variation in the following dimensions: (a) intracellular thiol content, (b) cell surface expression of glycan having N-acetyl-D-galactosaminyl residue as the terminal sugar, and (c) gene expression of thiol-synthesizing enzymes (CBS, MST, gamma-GCS, ODC, and TR), antimony-reducing enzymes (TDR and ACR2), and antimonial transporter genes (AQP1, MRPA, and PRP1). One of the isolates, T5, that was genotypically characterized as , caused Indian Kala-azar and was phenotypically Sb resistant (T5-LT-SSG-R), while the other two were , out of which one isolate, AG83, is antimony sensitive (AG83-LD-SSG-S) and the other isolate, T8, is Sb resistant (T8-LD-SSG-R). Our study showed that the Sb-resistant parasites, regardless of their genotype, showed significantly higher intracellular thiol compared with Sb-sensitive AG83-LD-SSG-S. Seemingly, T5-LT-SSG-R showed about 1.9-fold higher thiol content compared with T8-LD-SSG-R which essentially mirrored cell surface N-acetyl-D-galactosaminyl expression. Except TR, the expression of the remaining thiol-synthesizing genes was significantly higher in T8-LD-SSG-R and T5-LT-SSG-R than the sensitive one, and between the Sb-resistant parasites, the latter showed a significantly higher expression. Furthermore, the genes for Sb-reducing enzymes increased significantly in resistant parasites regardless of genotype compared with the sensitive one, and between two resistant parasites, there was hardly any difference in expression. Out of three antimony transporters, AQP1 was decreased with the concurrent increase in MRPA and PRP1 in resistant isolates when compared with the sensitive counterpart. Interestingly, no difference in expression of the above-mentioned transporters was noted between two Sb-resistant isolates. The enduring image that resonated from our study is that the genetically diverse Sb-resistant parasites showed enhanced thiol-synthesizing and antimony transporter gene expression than the sensitive counterpart to confer a resistant phenotype.
Topics: Humans; Leishmaniasis, Visceral; Antimony; Antiprotozoal Agents; Drug Resistance; Membrane Transport Proteins; Sulfhydryl Compounds
PubMed: 36405965
DOI: 10.3389/fcimb.2022.1021464 -
Chemistry (Weinheim An Der Bergstrasse,... Dec 2022The synthesis and characterisation of a library of acyclic antimony(III) and bismuth(III) triaryl pnictogen bonding (PnB) receptor systems are reported. In the...
The synthesis and characterisation of a library of acyclic antimony(III) and bismuth(III) triaryl pnictogen bonding (PnB) receptor systems are reported. In the first-generation receptor series, quantitative H NMR chloride titration experiments in THF solvent media reveal halide anion binding potency is intimately correlated with both the electronic-withdrawing nature of the aryl- substituent and the polarisability of the PnB donor. Further extensive anion binding investigations with the most potent Sb- and Bi-based PnB receptors: 1⋅Sb and 1⋅Bi , reveal novel selectivity profiles, both displaying Cl selectivity relative to the heavier halides and, impressively, to a range of highly basic oxoanions. The synthesis and preliminary chloride anion binding studies of a series of novel tripodal tris-proto-triazole triaryl Sb(III) and Bi(III) mixed PnB-HB receptor systems are also described. Whereas parent triphenyl Sb(III) and Bi(III) compounds are incapable of binding Cl in THF solvent media, the PnB-triazole HB host systems exhibit notable halide affinity.
Topics: Antimony; Bismuth; Chlorides; Anions; Halogens; Triazoles; Solvents
PubMed: 35968660
DOI: 10.1002/chem.202201838 -
Environmental Geochemistry and Health Nov 2020Mining activities are acknowledged to introduce contaminants into localised environments and cause wider spread diffuse pollution. The concentration, distribution and...
Mining activities are acknowledged to introduce contaminants into localised environments and cause wider spread diffuse pollution. The concentration, distribution and fate of arsenic (As) and antimony (Sb) were studied at the former metalliferous Louisa Mine at Glendinning, Scotland. Soils and surface water were sampled and subsequently analysed to map the distribution of contamination and identify pollution sources. The maximum concentrations of As and Sb of 15,490 and 1504.2 mg kg, respectively, were determined in soils associated with the ore processing area and spoil heaps. The fractions of dissolved As and Sb in soils were < 1 and < 5% of total soil content, respectively, confirming findings of previous studies that As and Sb are relatively immobile. Yet, the concentrations of As and Sb released by soils exceeded regulatory limits. Concentrations of As and Sb in surface water in the immediate vicinity of the mine were impacted by a gully discharge, but rapidly diluted. While the concentrations affected by the run-off waters did not exceed EU environmental standards for freshwater, the concentrations of both, As and Sb, sharply increased above the said environmental standards approximately 100 m downstream of the mine site. The unaltered As-to-Sb ratio in water samples suggests a geogenic source. While there is a justifiable concern about the soil pollution caused by the historic mining in the area, the Glenshanna Burn is affected more by indigenous geochemical processes than the derelict mine.
Topics: Antimony; Arsenic; Environment; Environmental Monitoring; Fresh Water; Mining; Scotland; Soil; Soil Pollutants; Water Pollutants, Chemical; Water Quality
PubMed: 32638254
DOI: 10.1007/s10653-020-00652-w -
Environment International Aug 2021Microorganisms can mediate arsenic (As) and antimony (Sb) transformation and thus change the As and Sb toxicity and mobility. The influence of As and Sb on the innate...
Arsenic and antimony co-contamination influences on soil microbial community composition and functions: Relevance to arsenic resistance and carbon, nitrogen, and sulfur cycling.
Microorganisms can mediate arsenic (As) and antimony (Sb) transformation and thus change the As and Sb toxicity and mobility. The influence of As and Sb on the innate microbiome has been extensively characterized. However, how microbial metabolic potentials are influenced by the As and Sb co-contamination is still ambiguous. In this study, we selected two contrasting sites located in the Shimen realgar mine, the largest realgar mine in Asia, to explore the adaptability and response of the soil microbiome to As and Sb co-contamination and the impact of co-contamination on microbial metabolic potentials. It is observed that the geochemical parameters, including the As and Sb fractions, were the driving forces that reshaped the community composition and metabolic potentials. Bacteria associated with Bradyrhizobium, Nocardioides, Sphingomonas, Burkholderia, and Streptomyces were predicted to be tolerant to high concentrations of As and Sb. Co-occurrence network analysis revealed that the genes related to C fixation, nitrate/nitrite reduction, N fixation, and sulfate reduction were positively correlated with the As and Sb fractions, suggesting that As and Sb biogeochemical cycling may interact with and benefit from C, N, and S cycling. The results suggest that As and Sb co-contamination not only influences As-related genes, but also influences other genes correlated with microbial C, N, and S cycling.
Topics: Antimony; Arsenic; Asia; Carbon; Environmental Monitoring; Microbiota; Nitrogen; Soil; Soil Pollutants; Sulfur
PubMed: 33812041
DOI: 10.1016/j.envint.2021.106522 -
Ecotoxicology and Environmental Safety May 2023Antimony (Sb) poses a significant threat to human health due to sharp increases in its exploitation and application globally, but few studies have explored the...
Antimony (Sb) poses a significant threat to human health due to sharp increases in its exploitation and application globally, but few studies have explored the pathophysiological mechanisms of acute hepatotoxicity induced by Sb exposure. We established an in vivo model to comprehensively explore the endogenous mechanisms underlying liver injury induced by short-term Sb exposure. Adult female and male Sprague-Dawley rats were orally administrated various concentrations of potassium antimony tartrate for 28 days. After exposure, the serum Sb concentration, liver-to-body weight ratio, and serum glucose levels significantly increased in a dose-dependent manner. Body weight gain and serum concentrations of biomarkers of hepatic injury (e.g., total cholesterol, total protein, alkaline phosphatase, and the aspartate aminotransferase/alanine aminotransferase ratio) decreased with increasing Sb exposure. Through integrative non-targeted metabolome and lipidome analyses, alanine, aspartate, and glutamate metabolism; phosphatidylcholines; sphingomyelins; and phosphatidylinositols were the most significantly affected pathways in female and male rats exposed to Sb. Additionally, correlation analysis showed that the concentrations of certain metabolites and lipids (e.g., deoxycholic acid, N-methylproline, palmitoylcarnitine, glycerophospholipids, sphingomyelins, and glycerol) were significantly associated with hepatic injury biomarkers, indicating that metabolic remodeling may be involved in apical hepatotoxicity. Our study demonstrated that short-term exposure to Sb induces hepatotoxicity, possibly through a glycolipid metabolism disorder, providing an important reference for the health risks of Sb pollution.
Topics: Humans; Rats; Male; Female; Animals; Rats, Sprague-Dawley; Antimony; Sphingomyelins; Chemical and Drug Induced Liver Injury; Biomarkers; Body Weight; Liver
PubMed: 37023648
DOI: 10.1016/j.ecoenv.2023.114852 -
International Journal of Environmental... Feb 2022Soils at primary explosives sites have been contaminated by high concentrations of antimony (Sb) and co-occurring heavy metals (Cu and Zn), and are largely overlooked...
Soils at primary explosives sites have been contaminated by high concentrations of antimony (Sb) and co-occurring heavy metals (Cu and Zn), and are largely overlooked and neglected. In this study, we investigated Sb concentrations and species and studied the effect of combined Fe- and Fe-Al-based sorbent application on the mobility of Sb and co-occurring metals. The content of Sb in soil samples varied from 26.7 to 4255.0 mg/kg. In batch experiments, FeSO showed ideal Sb sorption (up to 97% sorption with 10% FeSO·7HO), whereas the sorptions of 10% Fe and 10% goethite were 72% and 41%, respectively. However, Fe-based sorbents enhanced the mobility of co-occurring Cu and Zn to varying levels, especially FeSO·7HO. Al(OH) was required to prevent Cu and Zn mobilization. In this study, 5% FeSO·7HO and 4% Al(OH) mixed with soil was the optimal combination to solve this problem, with Sb, Zn, and Cu stabilizations of 94.6%, 74.2%, and 82.2%, respectively. Column tests spiked with 5% FeSO·7HO, and 4% Al(OH) showed significant Sb (85.85%), Zn (83.9%), and Cu (94.8%) retention. The pH-regulated results indicated that acid conditioning improved Sb retention under alkaline conditions. However, no significant difference was found between the acidification sets and those without pH regulation. The experimental results showed that 5% FeSO·7HO + 4% Al(OH) without pH regulation was effective for the stabilization of Sb and co-occurring metals in primary explosive soils.
Topics: Antimony; Explosive Agents; Metals, Heavy; Soil; Soil Pollutants
PubMed: 35206172
DOI: 10.3390/ijerph19041979 -
Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines.Parasites & Vectors Nov 2020One of the major challenges to leishmaniasis treatment is the emergence of parasites resistant to antimony. To study differentially expressed genes associated with drug... (Comparative Study)
Comparative Study
BACKGROUND
One of the major challenges to leishmaniasis treatment is the emergence of parasites resistant to antimony. To study differentially expressed genes associated with drug resistance, we performed a comparative transcriptomic analysis between wild-type and potassium antimonyl tartrate (Sb)-resistant Leishmania infantum lines using high-throughput RNA sequencing.
METHODS
All the cDNA libraries were constructed from promastigote forms of each line, sequenced and analyzed using STAR for mapping the reads against the reference genome (L. infantum JPCM5) and DESeq2 for differential expression statistical analyses. All the genes were functionally annotated using sequence similarity search.
RESULTS
The analytical pipeline considering an adjusted p-value < 0.05 and fold change > 2.0 identified 933 transcripts differentially expressed (DE) between wild-type and Sb-resistant L. infantum lines. Out of 933 DE transcripts, 504 presented functional annotation and 429 were assigned as hypothetical proteins. A total of 837 transcripts were upregulated and 96 were downregulated in the Sb-resistant L. infantum line. Using this DE dataset, the proteins were further grouped in functional classes according to the gene ontology database. The functional enrichment analysis for biological processes showed that the upregulated transcripts in the Sb-resistant line are associated with protein phosphorylation, microtubule-based movement, ubiquitination, host-parasite interaction, cellular process and other categories. The downregulated transcripts in the Sb-resistant line are assigned in the GO categories: ribonucleoprotein complex, ribosome biogenesis, rRNA processing, nucleosome assembly and translation.
CONCLUSIONS
The transcriptomic profile of L. infantum showed a robust set of genes from different metabolic pathways associated with the antimony resistance phenotype in this parasite. Our results address the complex and multifactorial antimony resistance mechanisms in Leishmania, identifying several candidate genes that may be further evaluated as molecular targets for chemotherapy of leishmaniasis.
Topics: Animals; Antimony; Antiprotozoal Agents; Drug Resistance; Leishmania infantum; Protozoan Proteins; Transcriptome
PubMed: 33256787
DOI: 10.1186/s13071-020-04486-4 -
The ISME Journal Jun 2022Antimony (Sb) contamination released from mine tailings represents a global threat to natural ecosystems and human health. The geochemical conditions of Sb tailings,...
Antimony (Sb) contamination released from mine tailings represents a global threat to natural ecosystems and human health. The geochemical conditions of Sb tailings, which are oligotrophic and replete in sulfur (S) and Sb, may promote the coupled metabolism of Sb and S. In this study, multiple lines of evidence indicate that a novel biogeochemical process, S oxidation coupled to Sb(V) reduction, is enzymatically mediated by Desulfurivibrio spp. The distribution of Desulfurivibrio covaried with S and Sb concentrations, showing a high relative abundance in Sb mine tailings but not in samples from surrounding sites (i.e., soils, paddies, and river sediments). Further, the metabolic potential to couple S oxidation to Sb(V) reduction, encoded by a non-canonical, oxidative sulfite reductase (dsr) and arsenate reductase (arrA) or antimonate reductase (anrA), respectively, was found to be common in Desulfurivibrio genomes retrieved from metal-contaminated sites in southern China. Elucidation of enzymatically-catalyzed S oxidation coupled to Sb(V) reduction expands the fundamental understanding of Sb biogeochemical cycling, which may be harnessed to improve remediation strategies for Sb mine tailings.
Topics: Antimony; Ecosystem; Humans; Oxidation-Reduction; Rivers; Soil; Sulfur
PubMed: 35132119
DOI: 10.1038/s41396-022-01201-2