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Cited by 31Pneumocystis jirovecii pneumonia detection and treatmentPneumonia and Respiratory InfectionsParasitic Infections and Diagnostics

Dihydrofolate reductase gene polymorphisms in Pneumocystis carinii f. sp. hominis in Japan.

TAKAHASHI, TAKASHI, ENDO, TOKIOMI, NAKAMURA, TETSUYA, SAKASHITA, HIROYUKI, KIMURA, KYOKO, OHNISHI, KENJI, KITAMURA, YOSHIHIRO, IWAMOTO, AIKICHI·2002·Journal of Medical Microbiology
DOI 10.1099/0022-1317-51-6-510
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Abstract

This study examined polymorphisms in the dihydrofolate reductase (DHFR) gene of Pneumocystis carinii isolates from 27 patients with P. carinii pneumonia (PCP) in Japan. Four substitution sites with two synonymous and two non-synonymous changes were found. Two synonymous substitutions at nucleotide positions 540 and 312 were identified in one and 13 patients, respectively. Two amino acid substitutions (Ala67Val, Cysl66Tyr) were found in two different patients. No linkage of amino acid substitutions in DHFR to those in dihydropteroate synthase was observed. The two patients whose isolates showed non-synonymous DHFR mutations were not exposed to DHFR inhibitors before they developed PCP and were treated successfully with co-trimoxazole.

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Crossref · 10.1099/0022-1317-51-6-510

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  • Two studies have failed to demonstrate an association between the use of TMP-SMX for PCP prophylaxis in HIV-infected persons and the presence of DHFR gene mutations.

    “To date, two studies have failed to demonstrate an association between the use of TMP-SMX for PCP prophylaxis in HIV-infected persons and the presence of DHFR gene mutations (21,36).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [36]

  • In the second study, 16 (59%) of 27 specimens had DHFR gene mutations, 14 had synonymous changes, and 2 had nonsynonymous changes.

    “In the second study, 16 (59%) of 27 specimens (from 27 patients, 19 of whom were HIV-infected) had DHFR gene mutations, 14 had synonymous changes, and 2 had nonsynonymous changes (36).”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [36]

  • This study reported that observed nonsynonymous changes in Pneumocystis DHFR were not in the highly conserved regions of the enzyme as are the amino acid substitutions that confer resistance to TMP (or pyrimethamine) in E. coli, Staphylococcus aureus, Streptococcus pneumoniae, and Plasmodium falciparum.

    “In addition, this study aligned the Pneumocystis DHFR sequences with those of E. coli, Staphylococcus aureus, Streptococcus pneumoniae, and Plasmodium falciparum and reported that the observed nonsynonymous changes in Pneumocystis DHFR were not in the highly conserved regions of the enzyme as are the amino acid substitutions that confer resistance to TMP (or pyrimethamine) in these other organisms”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [36]

  • Neither of the two patients whose PCP specimen had nonsynonymous DHFR changes had prior exposure to DHFR inhibitors, yet both patients were treated successfully for PCP with TMP-SMX.

    “Neither of the two patients whose PCP specimen had nonsynonymous DHFR changes had prior exposure to DHFR inhibitors, yet both patients were treated successfully for PCP with TMP-SMX.”

    From Dihydropteroate Synthase Gene Mutations in<i>Pneumocystis</i>and Sulfa Resistance (2004) · cites this paper as [36]

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Authors
TAKAHASHI, T., ENDO, T., NAKAMURA, T., SAKASHITA, H., KIMURA, K., OHNISHI, K., KITAMURA, Y., & IWAMOTO, A.
Affiliations
Tokyo Metropolitan Bokutoh Hospital (JP)
ORCID
Venue
Journal of Medical Microbiology
Publisher
Microbiology Society
Published
2002-06-01
Volume
51
Issue
6
Pages
510-515
ISSN
  • 0022-2615 (ISSN-L)
  • 1473-5644
DOI
10.1099/0022-1317-51-6-510
OpenAlex
W2101386304
Cited by
31
References
18
Citations by year
2022: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 2
FWCI
2.01
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medical Microbiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasitic Infections and Diagnostics
Keywords
dihydrofolate reductase, Pneumocystis carinii pneumonia, synonymous substitutions, amino acid substitutions, dihydropteroate synthase, drug resistance, Japan
MeSH terms
Amino Acid Sequence, Anti-Infective Agents, Base Sequence, Bronchoalveolar Lavage Fluid, Dihydropteroate Synthase, Gene Amplification, Genes, Fungal, Humans, Japan, Molecular Sequence Data, Mutation, Pneumocystis, Pneumonia, Pneumocystis, Polymorphism, Genetic, Tetrahydrofolate Dehydrogenase, Trimethoprim, Sulfamethoxazole Drug Combination, Polymerase Chain Reaction, Sequence Alignment, Immunocompromised Host, Treatment Failure, Sequence Analysis

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