ArticleAntimicrobial agents and chemotherapy2004
Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06431958 (Droplet Digital PCR and PCR-free BIOSensors for the Detection of Resistance-associated SNPs in Pneumocystis Jirovecii), which is not on this map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Droplet Digital PCR and PCR-free BIOSensors for the Detection of Resistance-associated SNPs in Pneumocystis Jirovecii
Who cites it
39 citing papers in PubMed, 95 citations in OpenAlex.
- Predicting antifolate resistance in the unculturable fungal pathogen Pneumocystis jirovecii.PLoS genetics · 2026Article
- Immune Responses toJournal of inflammation research · 2026Review
- Analysis of Mutations inInfection and drug resistance · 2024Article
- Apparent Absence of Selective Pressure on Pneumocystis jirovecii Organisms in Patients with Prior Methotrexate Exposure.Antimicrobial agents and chemotherapy · 2022Article
- Highly ConservedAntimicrobial agents and chemotherapy · 2022Article
- Fungal Genomics in Respiratory Medicine: What, How and When?Mycopathologia · 2021Review
- Consensus Multilocus Sequence Typing Scheme forJournal of fungi (Basel, Switzerland) · 2020Review
- Recent Advances in the Diagnosis and Management ofTuberculosis and respiratory diseases · 2020Review
- Genetic polymorphisms associated with treatment failure and mortality in pediatric Pneumocystosis.Scientific reports · 2019Article
- Site-Directed Mutagenesis of the 1,3-β-Glucan Synthase Catalytic Subunit ofAntimicrobial agents and chemotherapy · 2018Article
- A quantitative systems pharmacology (QSP) model for Pneumocystis treatment in mice.BMC systems biology · 2018Article
- A Molecular Window into the Biology and Epidemiology of Pneumocystis spp.Clinical microbiology reviews · 2018Review
- Targeting species specific amino acid residues: Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors and potential anti-opportunistic infection agents.Bioorganic & medicinal chemistry · 2018Article
- [Research progress on genes mutations related to sulfa drug resistance inZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2017Review
- Lausannevirus Encodes a Functional Dihydrofolate Reductase Susceptible to Proguanil.Antimicrobial agents and chemotherapy · 2017Article
- [Rapid diagnostic test for respiratory infections].Enfermedades infecciosas y microbiologia clinica · 2017Review
- A Quantitative Model to Estimate Drug Resistance in Pathogens.Journal of fungi (Basel, Switzerland) · 2016Article
- Diversity of Pneumocystis jirovecii during Infection Revealed by Ultra-Deep Pyrosequencing.Frontiers in microbiology · 2016Article
- Pneumocystis jirovecii--from a commensal to pathogen: clinical and diagnostic review.Parasitology research · 2015Review
- Pneumocystis jirovecii infection and the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations in HIV-positive individuals from Pune, India.Mycopathologia · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most drugs used for prevention and treatment of Pneumocystis jirovecii pneumonia target enzymes involved in the biosynthesis of folic acid, i.e., dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). Emergence of P. jirovecii drug resistance has been suggested by the association between failure of prophylaxis with sulfa drugs and mutations in DHPS. However, data on the occurrence of mutations in DHFR, the target of trimethoprim and pyrimethamine, are scarce. We examined polymorphisms in P. jirovecii DHFR from 33 patients diagnosed with P. jirovecii pneumonia who were receiving prophylaxis with a DHFR inhibitor (n = 15), prophylaxis without a DHFR inhibitor (n = 11), or no prophylaxis (n = 7). Compared to the wild-type sequence present in GenBank, 19 DHFR nucleotide substitution sites were found in 18 patients with 3 synonymous and 16 nonsynonymous mutations. Of 16 amino acid changes, 6 were located in positions conserved among distant organisms, and five of these six positions are probably involved in the putative active sites of the enzyme. Patients with failure of prophylaxis, including a DHFR inhibitor, were more likely to harbor nonsynonymous DHFR mutations than those who did not receive such prophylaxis (9 of 15 patients versus 2 of 18; P = 0.008). Analysis of the rate of nonsynonymous versus synonymous mutations was consistent with selection of amino acid substitutions in patients with failure of prophylaxis including a DHFR inhibitor. The results suggest that P. jirovecii populations may evolve under selective pressure from DHFR inhibitors, in particular pyrimethamine, and that DHFR mutations may contribute to P. jirovecii drug resistance.
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