| 1. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Elucidating selection processes for antibiotic resistance in sewage treatment plants using metagenomics
- 2016
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 572, s. 697-712
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Tidskriftsartikel (refereegranskat)abstract
- Sewage treatment plants (STPs) have repeatedly been suggested as “hotspots” for the emergence and dissemination of antibiotic-resistant bacteria. A critical question still unanswered is if selection pressures within STPs, caused by residual antibiotics or other co-selective agents, are sufficient to specifically promote resistance. To address this, we employed shotgun metagenomic sequencing of samples from different steps of the treatment process in three Swedish STPs. In parallel, concentrations of selected antibiotics, biocides and metals were analyzed. We found that concentrations of tetracycline and ciprofloxacin in the influent were above predicted concentrations for resistance selection, however, there was no consistent enrichment of resistance genes to any particular class of antibiotics in the STPs, neither for biocide and metal resistance genes. The most substantial change of the bacterial communities compared to human feces occurred already in the sewage pipes, manifested by a strong shift from obligate to facultative anaerobes. Through the treatment process, resistance genes against antibiotics, biocides and metals were not reduced to the same extent as fecal bacteria. The OXA-48 gene was consistently enriched in surplus and digested sludge. We find this worrying as OXA-48, still rare in Swedish clinical isolates, provides resistance to carbapenems, one of our most critically important classes of antibiotics. Taken together, metagenomics analyses did not provide clear support for specific antibiotic resistance selection. However, stronger selective forces affecting gross taxonomic composition, and with that resistance gene abundances, limit interpretability. Comprehensive analyses of resistant/non-resistant strains within relevant species are therefore warranted.
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| 2. |
- Flach, Carl-Fredrik, 1977, et al.
(författare)
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Does antifouling paint select for antibiotic resistance?
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 590, s. 461-468
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Tidskriftsartikel (refereegranskat)abstract
- There is concern that heavy metals and biocides contribute to the development of antibiotic resistance via co-selection. Most antifouling paints contain high amounts of such substances, which risks turning painted ship hulls into highly mobile refuges and breeding grounds for antibiotic-resistant bacteria. The objectives of this study were to start investigate if heavy-metal based antifouling paints can pose a risk for co-selection of antibiotic-resistant bacteria and, if so, identify the underlying genetic basis. Plastic panels with one side painted with copper and zinc-containing antifouling paint were submerged in a Swedish marina and biofilms from both sides of the panels were harvested after 2.5-4 weeks. DNA was isolated from the biofilms and subjected to metagenomic sequencing. Biofilm bacteria were cultured on marine agar supplemented with tetracycline, gentamicin, copper sulfate or zinc sulfate. Biofilm communities from painted surfaces displayed lower taxonomic diversity and enrichment of Gammaproteobacteria. Bacteria from these communities showed increased resistance to both heavy metals and tetracycline but not to gentamicin. Significantly higher abundance of metal and biocide resistance genes was observed, whereas mobile antibiotic resistance genes were not enriched in these communities. In contrast, we found an enrichment of chromosomal RND efflux system genes, including such with documented ability to confer decreased susceptibility to both antibiotics and biocides/heavy metals. This was paralleled by increased abundances of integron-associated integrase and ISCR transposase genes. The results show that the heavy metal-based antifouling paint exerts a strong selection pressure on marine bacterial communities and can co-select for certain antibiotic-resistant bacteria, likely by favoring species and strains carrying genes that provide cross-resistance. Although this does not indicate an immediate risk for promotion of mobile antibiotic resistance, the clear increase of genes involved in mobilizing DNA provides a foundation for increased opportunities for gene transfer in such communities, which might also involve yet unknown resistance mechanisms.
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| 3. |
- Andersson, Patrik, et al.
(författare)
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Multivariate modeling of polychlorinated biphenyl-induced CYP1A activity in hepatocytes from three different species : ranking scales and species differences
- 2000
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 19:5, s. 1454-1463
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Tidskriftsartikel (refereegranskat)abstract
- Cytochrome P4501A–induced activity of 20 selected polychlorinated biphenyls (PCBs) was evaluated by measuring ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities induced in the hepatocytes of cynomolgus monkeys, male castrated pigs, and chicken embryos. Quantitative structure-activity relationships have been established, including 52 physi-cochemical parameters and different measures of the dose-response curves. Relative effect potencies are predicted for the 154 tetra-to hepta-PCBs and reported for the most potent congeners according to both EC50 and maximal response values. Important physicochemical parameters of the PCBs as related to the modeled activity are parts of their ultraviolet absorption spectra, the Henry's law constant, the ionization potential, and the octanol-water partition coefficient. Interspecies differences were found in terms of varied sensitivity to different structural subgroups of the compounds. The chicken hepatocyte assay showed the most specific structure-activity relationship, with high activity for the non-ortho PCBs, whereas the pig hepatocytes responded even for some di- to tetra-ortho PCBs. An interspecies response, the principal induction potency, is presented for the 41 most potent PCBs. These responses showed strong correlation with the toxic equivalency factors and are likely to be useful in risk assessment of the compounds.
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| 4. |
- Cerveny, D., et al.
(författare)
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Neuroactive drugs and other pharmaceuticals found in blood plasma of wild European fish
- 2021
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Ingår i: Environmental International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- To gain a better understanding of which pharmaceuticals could pose a risk to fish, 94 pharmaceuticals representing 23 classes were analyzed in blood plasma from wild bream, chub, and roach captured at 18 sites in Germany, the Czech Republic and the UK, respectively. Based on read across from humans, we evaluated the risks of pharmacological effects occurring in the fish for each measured pharmaceutical. Twenty-three compounds were found in fish plasma, with the highest levels measured in chub from the Czech Republic. None of the German bream had detectable levels of pharmaceuticals, whereas roach from the Thames had mostly low concentrations. For two pharmaceuticals, four individual Czech fish had plasma concentrations higher than the concentrations reached in the blood of human patients taking the corresponding medication. For nine additional compounds, determined concentrations exceeded 10% of the corresponding human therapeutic plasma concentration in 12 fish. The majority of the pharmaceuticals where a clear risk for pharmacological effects was identified targets the central nervous system. These include e.g. flupentixol, haloperidol, and risperidone, all of which have the potential to affect fish behavior. In addition to identifying pharmaceuticals of environmental concern, the results emphasize the value of environmental monitoring of internal drug levels in aquatic wildlife, as well as the need for more research to establish concentration-response relationships. © 2020 The Author(s)
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| 5. |
- Fick, Jerker, et al.
(författare)
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Contamination of surface, ground, and drinking water from pharmaceutical production
- 2009
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Ingår i: Environmental Toxicology and Chemistry. - : SETAC Journals. - 0730-7268 .- 1552-8618. ; 28:12, s. 2522-2527
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Tidskriftsartikel (refereegranskat)abstract
- Low levels of pharmaceuticals are detected in surface, ground, and drinking water worldwide. Usage and incorrect disposal have been considered the major environmental sources of these micro-contaminants. Recent publications, however, suggest that wastewater from drug production can potentially be a source of much higher concentrations in certain locations. We investigated the environmental fate of active pharmaceutical ingredients in a major production area for the global bulk-drug market. Water samples were taken from a common effluent treatment plant near Hyderabad, India, which receives process water from about 90 bulk drug manufacturers. Surface water was analyzed from the recipient stream and from two lakes that are not contaminated by the treatment plant. Water samples were also taken from wells in six nearby villages. The samples were analyzed for the presence of twelve pharmaceuticals with LC-MS/MS. All wells were determined to be contaminated with drugs. Ciprofloxacin, enoxacin, cetirizine, terbinafine and citalopram were detected at >1microg l-1 in several wells. Very high concentrations of ciprofloxacin (up to 14 mg L-1) and other pharmaceuticals (up to 2 mg L-1) were found in the effluent of the treatment plant and in the two lakes (up to 6.5 mg L-1). Thus, insufficient wastewater treatment in one of the world's largest centers for bulk drug production leads to unprecedented drug contamination of surface, ground, and drinking water. This raises serious concerns regarding the development of antibiotic resistance, and it creates a major challenge for producers and regulatory agencies to improve the situation.
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| 6. |
- Fick, Jerker, et al.
(författare)
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Predicted critical environmental concentrations for 500 pharmaceuticals
- 2010
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier. - 0273-2300 .- 1096-0295. ; 58:3, s. 516-23
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Tidskriftsartikel (refereegranskat)abstract
- A growing number of pharmaceuticals are found in surface waters worldwide, raising concerns about their effects on aquatic organisms and it is a major challenge to develop a rational strategy for prioritizing drugs on which to focus the most extensive environmental research efforts. However, in contrast to most other chemicals, very good understanding of the human potency of pharmaceuticals has been obtained through efficacy and safety testing. Assuming that a drug acts primarily through the same target(s) also in a non-target species, it would be possible to predict the likelihood for pharmacological interactions in wildlife. Among aquatic organisms, fish most often share drug targets with humans. In this study, we have calculated the predicted critical environmental concentration (CECs), i.e. the surface water concentration expected to cause a pharmacological effect in fish, for 500 pharmaceuticals, assuming equivalent pharmacological activity. The CECs are based on literature data on human potencies together with a predicted bioconcentration factor in fish for each drug based on lipophilicity. We propose that CECs could be used as preliminary indicators of specific drugs' potential to cause adverse pharmacological effects at specific water concentrations, used when selecting pharmaceuticals to include in screening campaigns and for assessing relevant detection limits.
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| 7. |
- Fick, Jerker, et al.
(författare)
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Therapeutic levels of levonorgestrel detected in blood plasma of fish: results from screening rainbow trout exposed to treated sewage effluents.
- 2010
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Ingår i: Environmental science & technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:7, s. 2661-2666
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceuticals are found in surface waters worldwide, raising concerns about effects on aquatic organisms. Analyses of pharmaceuticals in blood plasma of fish could provide means to assess risk for pharmacological effects, as these concentrations could be compared with available human therapeutic plasma levels. In this study we investigated if fish exposed to sewage effluents have plasma concentrations of pharmaceuticals that are approaching human therapeutic levels. We also evaluated how well the bioconcentration of pharmaceuticals into fish blood plasma can be predicted based on lipophilicity. Rainbow trout were exposed to undiluted, treated sewage effluents at three sites in Sweden for 14 days. Levels of 25 pharmaceuticals in blood plasma and effluents were analyzed with liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-high resolution mass spectrometry. The progestin pharmaceutical levonorgestrel was detected in fish blood plasma at concentrations (8.5-12 ng mL(-1)), exceeding the human therapeutic plasma level. In total 16 pharmaceuticals were detected in fish plasma at concentrations higher than 1/1000 of the human therapeutic plasma concentration. Twenty-one pharmaceuticals were detected in either plasma or effluent, and 14 were detected in both compartments, allowing plasma bioconcentration factors to be determined. For 11 of these, theoretically calculated and experimentally measured values were in reasonably good agreement. However a few drugs, including levonorgestrel, did not bioconcentrate according to the screening model used. This study shows that rainbow trout exposed to sewage effluents have blood plasma levels of pharmaceuticals similar to human therapeutic concentrations, suggesting a risk for pharmacological effects in the fish. There is a particular concern about effects of progestin pharmaceuticals. For levonorgestrel, the measured effluent level (1 ng/L) was higher than water levels shown to reduce the fertility of fish.
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| 8. |
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| 9. |
- Lundström, Sara, 1981, et al.
(författare)
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Minimal selective concentrations of tetracycline in complex aquatic bacterial biofilms
- 2016
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 553, s. 587-95
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Tidskriftsartikel (refereegranskat)abstract
- Selection pressure generated by antibiotics released into the environment could enrich for antibiotic resistance genes and antibiotic resistant bacteria, thereby increasing the risk for transmission to humans and animals. Tetracyclines comprise an antibiotic class of great importance to both human and animal health. Accordingly, residues of tetracycline are commonly detected in aquatic environments. To assess if tetracycline pollution in aquatic environments promotes development of resistance, we determined minimal selective concentrations (MSCs) in biofilms of complex aquatic bacterial communities using both phenotypic and genotypic assays. Tetracycline significantly increased the relative abundance of resistant bacteria at 10 μg/L, while specific tet genes (tetA and tetG) increased significantly at the lowest concentration tested (1 μg/L). Taxonomic composition of the biofilm communities was altered with increasing tetracycline concentrations. Metagenomic analysis revealed a concurrent increase of several tet genes and a range of other genes providing resistance to different classes of antibiotics (e.g. cmlA, floR, sul1, and mphA), indicating potential for co-selection. Consequently, MSCs for the tet genes of ≤ 1 μg/L suggests that current exposure levels in e.g. sewage treatment plants could be sufficient to promote resistance. The methodology used here to assess MSCs could be applied in risk assessment of other antibiotics as well.
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| 10. |
- Tysklind, Mats, et al.
(författare)
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Selection of polychlorinated biphenyls for use in quantitative structure-activity modelling
- 1995
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Ingår i: SAR and QSAR in environmental research (Print). - : Informa UK Limited. - 1062-936X .- 1029-046X. ; 4:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- By characterizing the 154 tetra- through heptachlorinated biphenyl (PCB) congeners with a multitude of physico-chemical descriptors, a model representing chemical similarities and differences is achieved. The multivariate characterization of the PCBs was based on 47 physico-chemical descriptor variables, which were summarised by using principal component analysis (PCA). By applying statistical design to the orthogonal scores from the PCA, a 24-factorial design was used to select a set of 16 congeners. In addition, four congeners were added to provide information about the interior region of the chemical domain of PCBs. This set of 20 structurally different congeners is suggested to be used in future quantitative structure-activity relationships (QSARs) for screening of the toxicological and biochemical effects of the PCBs.
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