Dihydrofolate reductase gene polymorphisms in Pneumocystis carinii f. sp. hominis in Japan.
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.
Takahashi
Takashi
T
Endo
Tokiomi
T
Nakamura
Tetsuya
T
Division of Infectious Diseases, Advanced Clinical Research Center, *Department of Infectious Diseases and Applied Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 and Departments of †Internal Medicine and ‡Infectious Diseases, Tokyo Metropolitan Bokutoh General Hospital, Tokyo 130-0022, Japan.
Sakashita
Hiroyuki
H
Division of Infectious Diseases, Advanced Clinical Research Center, *Department of Infectious Diseases and Applied Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 and Departments of †Internal Medicine and ‡Infectious Diseases, Tokyo Metropolitan Bokutoh General Hospital, Tokyo 130-0022, Japan.
Kimura
Kyoko
K
Division of Infectious Diseases, Advanced Clinical Research Center, *Department of Infectious Diseases and Applied Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 and Departments of †Internal Medicine and ‡Infectious Diseases, Tokyo Metropolitan Bokutoh General Hospital, Tokyo 130-0022, Japan.
Ohnishi
Kenji
K
Division of Infectious Diseases, Advanced Clinical Research Center, *Department of Infectious Diseases and Applied Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 and Departments of †Internal Medicine and ‡Infectious Diseases, Tokyo Metropolitan Bokutoh General Hospital, Tokyo 130-0022, Japan.
Kitamura
Yoshihiro
Y
Iwamoto
Aikichi
A
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D004094:Dihydropteroate Synthase / Q000737:chemistry / Q000235:genetics; D005784:Gene Amplification; D005800:Genes, Fungal; D006801:Humans; D016867:Immunocompromised Host; D007564:Japan; D008969:Molecular Sequence Data; D009154:Mutation; D011010:Pneumocystis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D017421:Sequence Analysis; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017211:Treatment Failure; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase