ArticleEBioMedicine2021
The chemotherapeutic drug methotrexate selects for antibiotic resistance.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
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- Development of Pyrimido Pyridazine Analogs through Increased Whole Cell Target Engagement of the Dihydropteroate Synthase Pterin Binding Site in Gram-Negative Bacteria.ACS infectious diseases · 2025Article
- Pre-trained molecular representations enable antimicrobial discovery.Nature communications · 2025Article
- Exploring the Impact of Chemotherapy on the Emergence of Antibiotic Resistance in the Gut Microbiota of Colorectal Cancer Patients.Antibiotics (Basel, Switzerland) · 2025Review
- Co-selection for antibiotic resistance by environmental contaminants.npj antimicrobials and resistance · 2024Review
- Deep mutational scanning of Pneumocystis jirovecii dihydrofolate reductase reveals allosteric mechanism of resistance to an antifolate.PLoS genetics · 2024Article
- Multidrug Resistant Enteric Bacteria from Cancer Patients Admitted in Douala Laquintinie Hospital, Littoral Region of Cameroon.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2024Article
- Effect of chemotherapeutic agents on natural transformation frequency in Acinetobacter baylyi.Access microbiology · 2024Article
- Frequency of Fecal Carriage of ESBL Resistance Genes in Multidrug-ResistantInternational journal of microbiology · 2024Article
- Zinc effects on bacteria: insights frommSystems · 2023Article
- Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches.Microbiome research reports · 2023Article
- The interplay between anticancer challenges and the microbial communities from the gut.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2022Review
- Common themes in antimicrobial and anticancer drug resistance.Frontiers in microbiology · 2022Review
- A Microbiota-Dependent Response to Anticancer Treatment in anFrontiers in cellular and infection microbiology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUnderstanding drivers of antibiotic resistance evolution is fundamental for designing optimal treatment strategies and interventions to reduce the spread of antibiotic resistance. Various cytotoxic drugs used in cancer chemotherapy have antibacterial properties, but how bacterial populations are affected by these selective pressures is unknown. Here we test the hypothesis that the widely used cytotoxic drug methotrexate affects the evolution and selection of antibiotic resistance.
methodsFirst, we determined methotrexate susceptibility (IC
findingsWe show that methotrexate can select for acquired trimethoprim resistance determinants located on the chromosome or a plasmid. Additionally, methotrexate co-selects for genetically linked resistance determinants when present together with trimethoprim resistance on a multi-drug resistance plasmid. These selective effects occur at concentrations 40- to >320-fold below the methotrexate minimal inhibitory concentration.
interpretationOur results strongly suggest a selective role of methotrexate for virtually any antibiotic resistance determinant when present together with trimethoprim resistance on a multi-drug resistance plasmid. The presented results may have significant implications for patient groups strongly depending on effective antibiotic treatment.
fundingPJJ was supported by UiT The Arctic University of Norway and the Northern Norway Regional Health Authority (SFP1292-16/HNF1586-21) and JPI-EC-AMR (Project 271,176/H10). DIA was supported by the Swedish Research Council (grant 2017-01,527). The publication charges for this article have been funded by a grant from the publication fund of UiT The Arctic University of Norway.
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