Emerging pollutant metformin in water promotes the development of multiple-antibiotic resistance in Escherichia coli via chromosome mutagenesis

Wei, Zilin; Wei, Yijun; Li, Haibei; Shi, Danyang; Yang, Dong; Yin, Jing; Zhou, Shuqing; Chen, Tianjiao; Lǐ, Jùnwén; Jin, Min

doi:10.1016/j.jhazmat.2022.128474

Cited by 23 publications

(10 citation statements)

References 34 publications

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“…Environmental exposure to MET is increasingly recognized as an emerging issue threatening human health and ecological safety. ,,, Clearly, microorganisms are the vital drivers of MET degradation in the environment. Here, based on an investigation of MET contamination in wastewater from WWTPs and the MET degradation capacity of microorganisms from these wastewater samples, we isolated and characterized a MET-degrading bacterium Aminobacter sp.…”

Section: Results and Discussionmentioning

confidence: 99%

Aerobic Degradation of the Antidiabetic Drug Metformin by Aminobacter sp. Strain NyZ550

Zhou

2023

Environ. Sci. Technol.

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Metformin is becoming one of the most common emerging contaminants in surface and wastewater. Its biodegradation generally leads to the accumulation of guanylurea in the environment, but the microorganisms and mechanisms involved in this process remain elusive. Here, Aminobacter sp. strain NyZ550 was isolated and characterized for its ability to grow on metformin as a sole source of carbon, nitrogen, and energy under oxic conditions. This isolate also assimilated a variety of nitrogenous compounds, including dimethylamine. Hydrolysis of metformin by strain NyZ550 was accompanied by a stoichiometric accumulation of guanylurea as a dead-end product. Based on ion chromatography, gas chromatography−mass spectrometry, and comparative transcriptomic analyses, dimethylamine was identified as an additional hydrolytic product supporting the growth of the strain. Notably, a microbial mixture consisting of strain NyZ550 and an engineered Pseudomonas putida PaW340 expressing a guanylurea hydrolase was constructed for complete elimination of metformin and its persistent product guanylurea. Overall, our results not only provide new insights into the metformin biodegradation pathway, leading to the commonly observed accumulation of guanylurea in the environment, but also open doors for the complete degradation of the new pollutant metformin.

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Section: Results and Discussionmentioning

confidence: 99%

Aerobic Degradation of the Antidiabetic Drug Metformin by Aminobacter sp. Strain NyZ550

Zhou

2023

Environ. Sci. Technol.

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“…The extensive use of antibiotics and antimicrobials for human prescriptions, consumer products, aquaculture, and for veterinary purposes has been raised as a concern in Bangladesh, ,, not only due to their potential toxicity but also due to their potential to increase antibiotic-resistant pathogens. , Other organic micropollutants may also involuntarily trigger antibiotic-resistance in bacterial populations. A recent study highlighted DNA mutations leading to multiple-antibiotic resistance in Escherichia coli after an exposure to metformin, a pharmaceutical intended for type 2 diabetes treatment, after only 1 day of exposure at low concentrations from 1 ng/L . In addition to various antibiotics and antimicrobials (e.g., clarithromycin, cordycepin, sulfamethoxazole, and triclosan), metformin was detected in most of the current samples ( i.e.…”

Section: Resultsmentioning

confidence: 99%

“…A recent study highlighted DNA mutations leading to multiple-antibiotic resistance in Escherichia coli after an exposure to metformin, a pharmaceutical intended for type 2 diabetes treatment, after only 1 day of exposure at low concentrations from 1 ng/L. 107 In addition to various antibiotics and antimicrobials (e.g., clarithromycin, cordycepin, sulfamethoxazole, and triclosan), metformin was detected in most of the current samples ( i.e. , 10/12, Table 1 ) at a maximum concentration of 870 ng/L ( Table S53 ).…”

Section: Resultsmentioning

confidence: 99%

Nontarget Analysis of Polluted Surface Waters in Bangladesh Using Open Science Workflows

Bonnefille

Karlsson

Rian

et al. 2023

Environ. Sci. Technol.

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Nontarget mass spectrometry has great potential to reveal patterns of water contamination globally through community science, but few studies are conducted in low-income countries, nor with open-source workflows, and few datasets are FAIR (Findable, Accessible, Interoperable, Reusable). Water was collected from urban and rural rivers around Dhaka, Bangladesh, and analyzed by liquid chromatography high-resolution mass spectrometry in four ionization modes (electrospray ionization ±, atmospheric pressure chemical ionization ±) with data-independent MS2 acquisition. The acquisition strategy was complementary: 19,427 and 7365 features were unique to ESI and APCI, respectively. The complexity of water pollution was revealed by >26,000 unique molecular features resolved by MS-DIAL, among which >20,000 correlated with urban sources in Dhaka. A major wastewater treatment plant was not a dominant pollution source, consistent with major contributions from uncontrolled urban drainage, a result that encourages development of further wastewater infrastructures. Matching of deconvoluted MS2 spectra to public libraries resulted in 62 confident annotations (i.e., Level 1-2a) and allowed semiquantification of 42 analytes including pharmaceuticals, pesticides, and personal care products. In silico structure prediction for the top 100 unknown molecular features associated with an urban source allowed 15 additional chemicals of anthropogenic origin to be annotated (i.e., Level 3). The authentic MS2 spectra were uploaded to MassBank Europe, mass spectral data were openly shared on the MassIVE repository, a tool (i.e., MASST) that could be used for community science environmental surveillance was demonstrated, and current limitations were discussed.

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“…The expression of acrA , acrB , and TolC genes were specifically investigated since it has been previously suggested that diclofenac, metformin, and 17-β-estradiol are acrAB-TolC efflux pump substrates (39, 51, 55). However, there was no significant change in the expression of these genes resulting from NAD treatment (Kruskal-Wallis, acrA p=0.65, acrB p=0.61, TolC p=0.83).…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial effects, and selection for AMR by non-antibiotic drugs on bacterial communities

Hayes,

Zhang,

Feil

et al. 2024

Preprint

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Antimicrobial resistance (AMR) is a major threat to human, veterinary, and agricultural health. AMR can be directly selected for by antibiotics, and indirectly co-selected for by biocides and metals. Some evidence suggests that non-antibiotic drugs (NADs) can co-select for AMR, but previous work focused on exposing single model bacterial species to predominately high concentrations of NADs. Here, we determined the antimicrobial effect and selective potential of three commonly used NADs against a complex bacterial community using a combination of culture based, metagenomic, and metratranscriptomic approaches. We found that three of five NADs tested on growth significantly reduced growth of a bacterial community, although only one (17-β-estradiol) selected for an AMR marker using qPCR. Whole metagenome sequencing indicated that there was no clear strong selection by NADs for antibiotic resistance genes, nor effects on community composition. However, some changes in relative abundance of metal resistance genes were observed after exposure to diclofenac, metformin, and 17-β-estradiol. Together, these results indicate that the NADs tested likely do not strongly select for AMR at both clinically and environmentally relevant concentrations.

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Emerging pollutant metformin in water promotes the development of multiple-antibiotic resistance in Escherichia coli via chromosome mutagenesis

Cited by 23 publications

References 34 publications

Aerobic Degradation of the Antidiabetic Drug Metformin by Aminobacter sp. Strain NyZ550

Aerobic Degradation of the Antidiabetic Drug Metformin by Aminobacter sp. Strain NyZ550

Nontarget Analysis of Polluted Surface Waters in Bangladesh Using Open Science Workflows

Antimicrobial effects, and selection for AMR by non-antibiotic drugs on bacterial communities

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