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1.
Environ Int ; 150: 106436, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33592450

RESUMO

There is a risk that residues of antibiotics and other antimicrobials in hospital and municipal wastewaters could select for resistant bacteria. Still, direct experimental evidence for selection is lacking. Here, we investigated if effluent from a large Swedish hospital, as well as influent and effluent from the connected municipal wastewater treatment plant (WWTP) select for antibiotic resistant Escherichia coli in three controlled experimental setups. Exposure of sterile-filtered hospital effluent to a planktonic mix of 149 different E. coli wastewater isolates showed a strong selection of multi-resistant strains. Accordingly, exposure to a complex wastewater community selected for strains resistant to several antibiotic classes. Exposing individual strains with variable resistance patterns revealed a rapid bactericidal effect of hospital effluent on susceptible, but not multi-resistant E. coli. No selection was observed after exposure to WWTP effluent, while exposure to WWTP influent indicated a small selective effect for ceftazidime and cefadroxil resistant strains, and only in the E. coli mix assay. An analysis of commonly used antibiotics and non-antibiotic pharmaceuticals in combination with growth and resistance pattern of individual E. coli isolates suggested a possible contribution of ciprofloxacin and ß-lactams to the selection by hospital effluent. However, more research is needed to clarify the contribution from different selective agents. While this study does not indicate selection by the studied WWTP effluent, there is some indications of selective effects by municipal influent on ß-lactam-resistant strains. Such effects may be more pronounced in countries with higher antibiotic use than Sweden. Despite the limited antibiotic use in Sweden, the hospital effluent strongly and consistently selected for multi-resistance, indicating widespread risks. Hence, there is an urgent need for further evaluation of risks for resistance selection in hospital sewers, as well as for strategies to remove selective agents and resistant bacteria.

2.
Environ Pollut ; 276: 116733, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33631686

RESUMO

Horizontal gene transfer (HGT) plays an important role in the dissemination of antibiotic resistance genes. In sewer systems, human-associated and environmental bacteria are mixed together and exposed to many substances known to increase HGT, including various antibacterial compounds. In wastewaters, those substances are most often detected below concentrations known to induce HGT individually. Still, it is possible that such wastewaters induce HGT, for example via mixture effects. Here, a panel of antibiotics, biocides and other pharmaceuticals was measured in filter-sterilized municipal and hospital wastewater samples from Gothenburg, Sweden. The effects on HGT of the chemical mixtures in these samples were investigated by exposing a complex bacterial donor community together with a GFP-tagged E. coli recipient strain. Recipients that captured sulfonamide resistance-conferring mobile genetic elements (MGEs) from the bacterial community were enumerated and characterized by replicon typing, antibiotic susceptibility testing and long read sequencing. While exposure to municipal wastewater did not result in any detectable change in HGT rates, exposure to hospital wastewater was associated with an increase in the proportion of recipients that acquired sulfonamide resistance but also a drastic decrease in the total number of recipients. Although, concentrations were generally higher in hospital than municipal wastewater, none of the measured substances could individually explain the observed effects of hospital wastewater. The great majority of the MGEs captured were IncN plasmids, and resistance to several antibiotics was co-transferred in most cases. Taken together, the data show no evidence that chemicals present in the studied municipal wastewater induce HGT. Still, the increased relative abundance of transconjugants after exposure to hospital wastewater could have implications for the risks of both emergence and transmission of resistant bacteria.


Assuntos
Transferência Genética Horizontal , Águas Residuárias , Antibacterianos , Escherichia coli/genética , Hospitais , Humanos , Plasmídeos , Suécia
3.
Commun Biol ; 4(1): 8, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398069

RESUMO

Since the introduction of antibiotics as therapeutic agents, many bacterial pathogens have developed resistance to antibiotics. Mobile resistance genes, acquired through horizontal gene transfer, play an important role in this process. Understanding from which bacterial taxa these genes were mobilized, and whether their origin taxa share common traits, is critical for predicting which environments and conditions contribute to the emergence of novel resistance genes. This knowledge may prove valuable for limiting or delaying future transfer of novel resistance genes into pathogens. The literature on the origins of mobile resistance genes is scattered and based on evidence of variable quality. Here, we summarize, amend and scrutinize the evidence for 37 proposed origins of mobile resistance genes. Using state-of-the-art genomic analyses, we supplement and evaluate the evidence based on well-defined criteria. Nineteen percent of reported origins did not fulfill the criteria to confidently assign the respective origin. Of the curated origin taxa, >90% have been associated with infection in humans or domestic animals, some taxa being the origin of several different resistance genes. The clinical emergence of these resistance genes appears to be a consequence of antibiotic selection pressure on taxa that are permanently or transiently associated with the human/domestic animal microbiome.

4.
J Antimicrob Chemother ; 76(1): 117-123, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33005957

RESUMO

BACKGROUND: Metallo-ß-lactamases (MBLs) are enzymes that use zinc-dependent hydrolysis to confer resistance to almost all available ß-lactam antibiotics. They are hypothesized to originate from commensal and environmental bacteria, from where some have mobilized and transferred horizontally to pathogens. The current phylogeny of MBLs, however, is biased as it is founded largely on genes encountered in pathogenic bacteria. This incompleteness is emphasized by recent findings of environmental MBLs with new forms of zinc binding sites and atypical functional profiles. OBJECTIVES: To expand the phylogeny of MBLs to provide a more accurate view of their evolutionary history. METHODS: We searched more than 16 terabases of genomic and metagenomic data for MBLs of the three subclasses B1, B2 and B3 using the validated fARGene method. Predicted genes, together with the previously known ones, were used to infer phylogenetic trees. RESULTS: We identified 2290 unique MBL genes forming 817 gene families, of which 741 were previously uncharacterized. MBLs from subclasses B1 and B3 separated into distinct monophyletic groups, in agreement with their taxonomic and functional properties. We present evidence that clinically associated MBLs were mobilized from Proteobacteria. Additionally, we identified three new variants of the zinc binding sites, indicating that the functional repertoire is broader than previously reported. CONCLUSIONS: Based on our results, we recommend that the nomenclature of MBLs is refined into the phylogenetic groups B1.1-B1.5 and B3.1-B3.4 that more accurately describe their molecular and functional characteristics. Our results will also facilitate the annotation of novel MBLs, reflecting their taxonomic organization and evolutionary origin.

5.
Commun Biol ; 3(1): 711, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33244050

RESUMO

Antibiotic resistance surveillance through regional and up-to-date testing of clinical isolates is a foundation for implementing effective empirical treatment. Surveillance data also provides an overview of geographical and temporal changes that are invaluable for guiding interventions. Still, due to limited infrastructure and resources, clinical surveillance data is lacking in many parts of the world. Given that sewage is largely made up of human fecal bacteria from many people, sewage epidemiology could provide a cost-efficient strategy to partly fill the current gap in clinical surveillance of antibiotic resistance. Here we explored the potential of sewage metagenomic data to assess clinical antibiotic resistance prevalence using environmental and clinical surveillance data from across the world. The sewage resistome correlated to clinical surveillance data of invasive Escherichia coli isolates, but none of several tested approaches provided a sufficient resolution for clear discrimination between resistance towards different classes of antibiotics. However, in combination with socioeconomic data, the overall clinical resistance situation could be predicted with good precision. We conclude that analyses of bacterial genes in sewage could contribute to informing management of antibiotic resistance.

6.
Environ Int ; 146: 106188, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33096467

RESUMO

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.

7.
Microb Genom ; 6(11)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33125315

RESUMO

Tetracyclines are broad-spectrum antibiotics used to prevent or treat a variety of bacterial infections. Resistance is often mediated through mobile resistance genes, which encode one of the three main mechanisms: active efflux, ribosomal target protection or enzymatic degradation. In the last few decades, a large number of new tetracycline-resistance genes have been discovered in clinical settings. These genes are hypothesized to originate from environmental and commensal bacteria, but the diversity of tetracycline-resistance determinants that have not yet been mobilized into pathogens is unknown. In this study, we aimed to characterize the potential tetracycline resistome by screening genomic and metagenomic data for novel resistance genes. By using probabilistic models, we predicted 1254 unique putative tetracycline resistance genes, representing 195 gene families (<70 % amino acid sequence identity), whereof 164 families had not been described previously. Out of 17 predicted genes selected for experimental verification, 7 induced a resistance phenotype in an Escherichia coli host. Several of the predicted genes were located on mobile genetic elements or in regions that indicated mobility, suggesting that they easily can be shared between bacteria. Furthermore, phylogenetic analysis indicated several events of horizontal gene transfer between bacterial phyla. Our results also suggested that acquired efflux pumps originate from proteobacterial species, while ribosomal protection genes have been mobilized from Firmicutes and Actinobacteria. This study significantly expands the knowledge of known and putatively novel tetracycline resistance genes, their mobility and evolutionary history. The study also provides insights into the unknown resistome and genes that may be encountered in clinical settings in the future.

8.
Antimicrob Agents Chemother ; 64(12)2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-32958716

RESUMO

Comparative genomics identified the environmental bacterial genus Shinella as the most likely origin of the class A carbapenemases BKC-1 and GPC-1. Available sequences and PCR analyses of additional Shinella species revealed homologous ß-lactamases showing up to 85.4% and 93.3% amino acid identity to both enzymes, respectively. The genes conferred resistance to ß-lactams once expressed in Escherichia coli bla BKC-1 likely evolved from a putative ancestral Shinella gene with higher homology through duplication of a gene fragment.

9.
mSphere ; 5(5)2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878926

RESUMO

Insertion sequences (ISs) are abundant mobile genetic elements on bacterial genomes, responsible for mobilization of many genes, including antibiotic resistance genes (ARGs). As ARGs often occur in similar genetic contexts, understanding which ISs tend to be associated with known ARGs could be a first step toward discovering novel ARGs through predictive or experimental strategies. This could be valuable, as early identification of ARGs in pathogens could facilitate surveillance, confinement actions, molecular diagnostics, and drug development. Here, we present a comprehensive analysis of the association of specific ISs with known ARGs. A large collection of bacterial genomes was used to characterize the immediate context of 2,437 known ARGs and 3,768 ISs. While many ARGs were consistently found close to specific ISs, the contexts around all ISs were more variable. Nevertheless, a subset of individual ISs, as well as tentative composite transposons, showed significant associations with ARGs. These included, e.g., insertion sequences classified as IS6, Tn3, IS4, and IS1 that were not only strongly associated with diverse ARGs but also highly abundant in pathogens. Therefore, we conclude that the context of this subset of ISs and tentative composite transposons would be particularly valuable to discover novel ARGs through modeling or empirical approaches. A set of 1,891 metagenomes were analyzed to identify environments where those ISs commonly associated with ARGs were particularly abundant. The associations found in metagenomes were similar to those found in genomes.IMPORTANCE The emergence and spread of antibiotic resistance genes (ARGs) among pathogens threaten the prevention and treatment of bacterial infections as well as our food production chains. Early knowledge about mobile ARGs that are present in pathogens or that have the potential to become clinically relevant could help mitigate potential negative consequences. Recently, exploring integron gene cassettes was shown to be successful for identifying novel mobilized ARGs, some of which were already circulating in pathogens. Still, only a subset of ARGs is mobilized by integrons, and the contexts of other mobile genetic elements associated with ARGs remain unexplored. This includes insertion sequences (ISs) responsible for the mobilization of many ARGs. Our analyses identified ISs, species, and environments where ARG-IS relationships are particularly strong. This could be a first step to guide the discovery of novel ARGs, while also providing insights into mechanisms involved in the mobilization and transfer of ARGs.

10.
Environ Int ; 144: 106083, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32890888

RESUMO

Antibiotic resistance presents a serious and still growing threat to human health. Environmental exposure levels required to select for resistance are unknown for most antibiotics. Here, we evaluated different experimental approaches and ways to interpret effect measures, in order to identify what concentration of trimethoprim that are likely to select for resistance in aquatic environments. When grown in complex biofilms, selection for resistant E. coli increased at 100 µg/L, whereas there was only a non-significant trend with regards to changes in taxonomic composition within the tested range (0-100 µg/L). Planktonic co-culturing of 149 different E. coli strains isolated from sewage again confirmed selection at 100 µg/L. Finally, pairwise competition experiments were performed with engineered E. coli strains carrying different trimethoprim resistance genes (dfr) and their sensitive counterparts. While strains with introduced resistance genes grew slower than the sensitive ones at 0 and 10 µg/L, a significant reduction in cost was found already at 10 µg/L. Defining lowest effect concentrations by comparing proportion of resistant strains to sensitive ones at the same time point, rather than to their initial ratios, will reflect the advantage a resistance factor can bring, while ignoring exposure-independent fitness costs. As costs are likely to be highly dependent on the specific environmental and genetic contexts, the former approach might be more suitable as a basis for defining exposure limits with the intention to prevent selection for resistance. Based on the present and other studies, we propose that 1 µg/L would be a reasonably protective exposure limit for trimethoprim in aquatic environments.

11.
Aquat Toxicol ; 227: 105583, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32835849

RESUMO

The presence of diclofenac in the aquatic environment and the risks for aquatic wildlife, especially fish, have been raised in several studies. One way to manage risks without enforcing improved wastewater treatment would be to substitute diclofenac (when suitable from a clinical perspective) with another non-steroidal anti-inflammatory drug (NSAID) associated with less environmental risk. While there are many ecotoxicity-studies of different NSAIDs, they vary extensively in set-up, species studied, endpoints and reporting format, making direct comparisons difficult. We previously published a comprehensive study on the effects of diclofenac in the three-spined stickleback (Gasterosteus aculeatus). Our present aim was to generate relevant effect data for another NSAID (naproxen) using a very similar setup, which also allowed direct comparisons with diclofenac regarding hazards and risks. Sticklebacks were therefore exposed to naproxen in flow-through systems for 27 days. Triplicate aquaria with 20 fish per aquarium were used for each concentration (0, 18, 70, 299 or 1232 µg/L). We investigated bioconcentration, hepatic gene expression, jaw lesions, kidney and liver histology. On day 21, mortalities in the highest exposure concentration group unexpectedly reached ≥ 25 % in all three replicate aquaria, leading us to terminate and sample that group the same day. On the last day (day 27), the mortality was also significantly increased in the second highest exposure concentration group. Increased renal hematopoietic hyperplasia was observed in fish exposed to 299 and 1232 µg/L. This represents considerably higher concentrations than those expected in surface waters as a result of naproxen use. Such effects were observed already at 4.6 µg/L in the experiment with diclofenac (lowest tested concentration). Similar to the responses to diclofenac, a concentration-dependent increase in both relative hepatic gene expression of c7 (complement component 7) and jaw lesions were observed, again at concentrations considerably higher than expected in surface waters. Naproxen bioconcentrated less than diclofenac, in line with the observed effect data. An analysis of recent sales data and reported concentrations in treated sewage effluent in Sweden suggest that despite higher dosages used for naproxen, a complete substitution would only be expected to double naproxen emissions. In summary, naproxen and diclofenac produce highly similar effects in fish but the environmental hazards and risks are clearly lower for naproxen. Hence, if there are concerns for environmental risks to fish with diclofenac, a substitution would be advisable when naproxen presents an adequate alternative from a clinical point-of-view.


Assuntos
Bioacumulação , Diclofenaco/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Naproxeno/toxicidade , Smegmamorpha/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Diclofenaco/metabolismo , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Humanos , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Modelos Teóricos , Naproxeno/metabolismo , Smegmamorpha/genética , Suécia , Poluentes Químicos da Água/metabolismo
13.
FEBS Open Bio ; 10(9): 1821-1832, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32683794

RESUMO

Carbapenemases are the main cause of carbapenem resistance in Gram-negative bacteria. How ß-lactamases with weak carbapenemase activity, such as the OXA-10-type class D ß-lactamases, contribute to anti-bacterial drug resistance is unclear. OXA-655 is a T26M and V117L OXA-10 variant, recently identified from hospital wastewater. Despite exhibiting stronger carbapenemase activity towards ertapenem (ETP) and meropenem (MEM) in Escherichia coli, OXA-655 exhibits reduced activity towards oxyimino-substituted ß-lactams like ceftazidime. Here, we have solved crystal structures of OXA-10 in complex with imipenem (IPM) and ETP, and OXA-655 in complex with MEM in order to unravel the structure-function relationship and the impact of residue 117 in enzyme catalysis. The new crystal structures show that L117 is situated at a critical position with enhanced Van der Waals interactions to L155 in the omega loop. This restricts the movements of L155 and could explain the reduced ability for OXA-655 to bind a bulky oxyimino group. The V117L replacement in OXA-655 makes the active site S67 and the carboxylated K70 more water exposed. This could affect the supply of new deacylation water molecules required for hydrolysis and possibly the carboxylation rate of K70. But most importantly, L117 leaves more space for binding of the hydroxyethyl group in carbapenems. In summary, the crystal structures highlight the importance of residue 117 in OXA-10 variants for carbapenemase activity. This study also illustrates the impact of a single amino acid substitution on the substrate profile of OXA-10 and the evolutionary potential of new OXA-10 variants.

14.
J Antimicrob Chemother ; 75(9): 2554-2563, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32464640

RESUMO

BACKGROUND: MBLs form a large and heterogeneous group of bacterial enzymes conferring resistance to ß-lactam antibiotics, including carbapenems. A large environmental reservoir of MBLs has been identified, which can act as a source for transfer into human pathogens. Therefore, structural investigation of environmental and clinically rare MBLs can give new insights into structure-activity relationships to explore the role of catalytic and second shell residues, which are under selective pressure. OBJECTIVES: To investigate the structure and activity of the environmental subclass B1 MBLs MYO-1, SHD-1 and ECV-1. METHODS: The respective genes of these MBLs were cloned into vectors and expressed in Escherichia coli. Purified enzymes were characterized with respect to their catalytic efficiency (kcat/Km). The enzymatic activities and MICs were determined for a panel of different ß-lactams, including penicillins, cephalosporins and carbapenems. Thermostability was measured and structures were solved using X-ray crystallography (MYO-1 and ECV-1) or generated by homology modelling (SHD-1). RESULTS: Expression of the environmental MBLs in E. coli resulted in the characteristic MBL profile, not affecting aztreonam susceptibility and decreasing susceptibility to carbapenems, cephalosporins and penicillins. The purified enzymes showed variable catalytic activity in the order of <5% to ∼70% compared with the clinically widespread NDM-1. The thermostability of ECV-1 and SHD-1 was up to 8°C higher than that of MYO-1 and NDM-1. Using solved structures and molecular modelling, we identified differences in their second shell composition, possibly responsible for their relatively low hydrolytic activity. CONCLUSIONS: These results show the importance of environmental species acting as reservoirs for MBL-encoding genes.

15.
PLoS Biol ; 18(4): e3000698, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32243442

RESUMO

Have you ever sought to use metagenomic DNA sequences reported in scientific publications? Were you successful? Here, we reveal that metagenomes from no fewer than 20% of the papers found in our literature search, published between 2016 and 2019, were not deposited in a repository or were simply inaccessible. The proportion of inaccessible data within the literature has been increasing year-on-year. Noncompliance with Open Data is best predicted by the scientific discipline of the journal. The number of citations, journal type (e.g., Open Access or subscription journals), and publisher are not good predictors of data accessibility. However, many publications in high-impact factor journals do display a higher likelihood of accessible metagenomic data sets. Twenty-first century science demands compliance with the ethical standard of data sharing of metagenomes and DNA sequence data more broadly. Data accessibility must become one of the routine and mandatory components of manuscript submissions-a requirement that should be applicable across the increasing number of disciplines using metagenomics. Compliance must be ensured and reinforced by funders, publishers, editors, reviewers, and, ultimately, the authors.


Assuntos
Acesso à Informação , Metagenoma , Publicações/estatística & dados numéricos , Bibliometria , Fator de Impacto de Revistas , Publicação de Acesso Aberto
16.
Antibiotics (Basel) ; 9(3)2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32183280

RESUMO

AmpC-type ß-lactamases severely impair treatment of many bacterial infections, due to their broad spectrum (they hydrolyze virtually all ß-lactams, except fourth-generation cephalosporins and carbapenems) and the increasing incidence of plasmid-mediated versions. The original chromosomal AmpCs are often tightly regulated, and their expression is induced in response to exposure to ß-lactams. Regulation of mobile ampC expression is in many cases less controlled, giving rise to constitutively resistant strains with increased potential for development or acquisition of additional resistances. We present here the identification of two integron-encoded ampC genes, blaIDC-1 and blaIDC-2 (integron-derived cephalosporinase), with less than 85% amino acid sequence identity to any previously annotated AmpC. While their resistance pattern identifies them as class C ß-lactamases, their low isoelectric point (pI) values make differentiation from other ß-lactamases by isoelectric focusing impossible. To the best of our knowledge, this is the first evidence of an ampC gene cassette within a class 1 integron, providing a mobile context with profound potential for transfer and spread into clinics. It also allows bacteria to adapt expression levels, and thus reduce fitness costs, e.g., by cassette-reshuffling. Analyses of public metagenomes, including sewage metagenomes, show that the discovered ampCs are primarily found in Asian countries.

17.
Microbiome ; 8(1): 41, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197644

RESUMO

BACKGROUND: New antibiotic resistance determinants are generally discovered too late, long after they have irreversibly emerged in pathogens and spread widely. Early discovery of resistance genes, before or soon after their transfer to pathogens could allow more effective measures to monitor and reduce spread, and facilitate genetics-based diagnostics. RESULTS: We modified a functional metagenomics approach followed by in silico filtering of known resistance genes to discover novel, mobilised resistance genes in class 1 integrons in wastewater-impacted environments. We identified an integron-borne gene cassette encoding a protein that conveys high-level resistance against aminoglycosides with a garosamine moiety when expressed in E. coli. The gene is named gar (garosamine-specific aminoglycoside resistance) after its specificity. It contains none of the functional domains of known aminoglycoside modifying enzymes, but bears characteristics of a kinase. By searching public databases, we found that the gene occurs in three sequenced, multi-resistant clinical isolates (two Pseudomonas aeruginosa and one Luteimonas sp.) from Italy and China, respectively, as well as in two food-borne Salmonella enterica isolates from the USA. In all cases, gar has escaped discovery until now. CONCLUSION: To the best of our knowledge, this is the first time a novel resistance gene, present in clinical isolates, has been discovered by exploring the environmental microbiome. The gar gene has spread horizontally to different species on at least three continents, further limiting treatment options for bacterial infections. Its specificity to garosamine-containing aminoglycosides may reduce the usefulness of the newest semisynthetic aminoglycoside plazomicin, which is designed to avoid common aminoglycoside resistance mechanisms. Since the gene appears to be not yet common in the clinics, the data presented here enables early surveillance and maybe even mitigation of its spread.

18.
Environ Pollut ; 261: 114200, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32220750

RESUMO

Antibiotic resistance surveillance data is lacking in many parts of the world, limiting effective therapy and management of resistance development. Analysis of urban wastewater, which contains bacteria from thousands of individuals, opens up possibilities to generate informative surveillance data in a standardized and resource-efficient way. Here, we evaluate the relationship between antibiotic resistance prevalence in E. coli from wastewater and clinical samples by studying countries with different resistance situations as assessed by traditional clinical surveillance. Composite, influent wastewater samples were collected over 24 h from treatment plants serving major cities in ten European countries. Using a broth screening method, resistance to six antibiotic classes was analyzed for 2507 E. coli isolates (n = 247-252 per country). Resistance prevalence in wastewater E. coli was compared to that in clinical E. coli reported by the European Antibiotic Resistance Surveillance Network. Resistance prevalence was lower in wastewater than clinical E. coli but followed similar geographic trends. Significant relationships were found for resistance to aminopenicillins (R2 = 0.72, p = 0.0019) and fluoroquinolones (R2 = 0.62, p = 0.0072), but not for aminoglycosides (R2 = 0.13, p = 0.31) and third-generation cephalosporins (R2 = 0.00, p = 0.99) where regression analyses were based on considerably fewer resistant isolates. When all four antibiotic classes were taken into account, the relationship was strong (R2 = 0.85, p < 0.0001). Carbapenem resistance was rare in both wastewater and clinical isolates. Wastewater monitoring shows promise as method for generating surveillance data reflecting the clinical prevalence of antibiotic resistant bacteria. Such data may become especially valuable in regions where clinical surveillance is currently limited.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Microbiologia Ambiental , Escherichia coli , Águas Residuárias , Antibacterianos/farmacologia , Monitoramento Ambiental , Escherichia coli/efeitos dos fármacos , Europa (Continente) , População Urbana , Águas Residuárias/microbiologia
19.
Lancet Infect Dis ; 20(4): e51-e60, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32059790

RESUMO

In 2013, a Lancet Infectious Diseases Commission described the state of antimicrobial resistance worldwide. Since then, greater awareness of the public health ramifications of antimicrobial resistance has led to national actions and global initiatives, including a resolution at the high-level meeting of the UN General Assembly in 2016. Progress in addressing this issue has ranged from a ban on irrational drug combinations in India to commitments to ban colistin as a growth promoter in animals, improve hospital infection control, and implement better antimicrobial stewardship. Funds have been mobilised, and regulatory barriers to new antibiotic development have been relaxed. These efforts have been episodic and uneven across countries, however. Sustained funding for antimicrobial resistance and globally harmonised targets to monitor progress are still urgently needed. Except for in a few leading countries, antimicrobial resistance has not captured the sustained focus of national leaders and country-level actors, including care providers.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/organização & administração , Farmacorresistência Bacteriana , Uso de Medicamentos/normas , Saúde Pública , Animais , Colistina/efeitos adversos , Países Desenvolvidos , Países em Desenvolvimento , Saúde Global , Humanos , Controle de Infecções/organização & administração
20.
Environ Int ; 137: 105339, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32036119

RESUMO

The widespread practice of applying sewage sludge to arable land makes use of nutrients indispensable for crops and reduces the need for inorganic fertilizer, however this application also provides a potential route for human exposure to chemical contaminants and microbial pathogens in the sludge. A recent concern is that such practice could promote environmental selection and dissemination of antibiotic resistant bacteria or resistance genes. Understanding the risks of sludge amendment in relation to antibiotic resistance development is important for sustainable agriculture, waste treatment and infectious disease management. To assess such risks, we took advantage of an agricultural field trial in southern Sweden, where land used for growing different crops has been amended with sludge every four years since 1981. We sampled raw, semi-digested and digested and stored sludge together with soils from the experimental plots before and two weeks after the most recent amendment in 2017. Levels of selected antimicrobials and bioavailable metals were determined and microbial effects were evaluated using both culture-independent metagenome sequencing and conventional culturing. Antimicrobials or bioavailable metals (Cu and Zn) did not accumulate to levels of concern for environmental selection of antibiotic resistance, and no coherent signs, neither on short or long time scales, of enrichment of antibiotic-resistant bacteria or resistance genes were found in soils amended with digested and stored sewage sludge in doses up to 12 metric tons per hectare. Likewise, only very few and slight differences in microbial community composition were observed after sludge amendment. Taken together, the current study does not indicate risks of sludge amendment related to antibiotic resistance development under the given conditions. Extrapolations should however be done with care as sludge quality and application practices vary between regions. Hence, the antibiotic concentrations and resistance load of the sludge are likely to be higher in regions with larger antibiotic consumption and resistance burden than Sweden.


Assuntos
Bactérias , Farmacorresistência Bacteriana , Fertilizantes , Poluentes do Solo , Solo , Agricultura , Fazendas , Humanos , Esgotos , Microbiologia do Solo , Suécia
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