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

TAKASHI TAKAHASHI, TOKIOMI ENDO, TETSUYA NAKAMURA^*, HIROYUKI SAKASHITA, KYOKO KIMURA, KENJI OHNISHI, YOSHIHIRO KITAMURA and AIKICHI IWAMOTO

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

Corresponding author: Dr T. Takahashi (e-mail: takahata{at}ims.u-tokyo.ac.jp).

Received 21 May 2001; final revised version received 28 Dec. 2001; accepted 9 Jan. 2002.

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, Cys166Tyr) 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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