Trimethoprim resistance in surface and wastewater is mediated by contrasting variants of the dfrB gene

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Trimethoprim (TMP) is a low-cost, widely prescribed antibiotic. Its effectiveness is increasingly challenged by the spread of genes coding for TMP-resistant dihydrofolate reductases: dfrA, and the lesser-known, evolutionarily unrelated dfrB. Despite recent reports of novel variants conferring high level TMP resistance (dfrB10 to dfrB21), the prevalence of dfrB is still unknown due to underreporting, heterogeneity of the analyzed genetic material in terms of isolation sources, and limited bioinformatic processing. In this study, we explored a coherent set of shotgun metagenomic sequences to quantitatively estimate the abundance of dfrB gene variants in aquatic environments. Specifically, we scanned sequences originating from influents and effluents of municipal sewage treatment plants as well as river-borne microbiomes. Our analyses reveal an increased prevalence of dfrB1, dfrB2, dfrB3, dfrB4, dfrB5, and dfrB7 in wastewater microbiomes as compared to freshwater. These gene variants were frequently found in genomic neighborship with other resistance genes, transposable elements, and integrons, indicating their mobility. By contrast, the relative abundances of the more recently discovered variants dfrB9, dfrB10, and dfrB13 were significantly higher in freshwater than in wastewater microbiomes. Moreover, their direct neighborship with other resistance genes or markers of mobile genetic elements was significantly less likely. Our findings suggest that natural freshwater communities form a major reservoir of the recently discovered dfrB gene variants. Their proliferation and mobilization in response to the exposure of freshwater communities to selective TMP concentrations may promote the prevalence of high-level TMP resistance and thus limit the future effectiveness of antimicrobial therapies.

Details

Original languageEnglish
Pages (from-to)1455-1466
Number of pages12
JournalISME Journal
Volume17
Issue number9
Publication statusPublished - Sept 2023
Peer-reviewedYes

External IDs

PubMed 37369703
Scopus 85163281042
ORCID /0000-0002-6048-6984/work/142240088
ORCID /0000-0001-5372-0923/work/142242993
ORCID /0000-0002-9301-1803/work/161409835

Keywords

Sustainable Development Goals

Keywords

  • Antibiotic-resistance, Dihydrofolate-reductase, Escherichia-coli, Antimicrobial resistance, Cassette arrays, Identification, Susceptibility, Mechanisms, Integrons, Plasmids, Trimethoprim Resistance/genetics, Wastewater, Genes, Bacterial, Trimethoprim/pharmacology, Anti-Bacterial Agents/pharmacology

Library keywords