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  • Title: Genetic diversity of drug targets including dihydropteroate synthase, dihydrofolate reductase and cytochrome b, in Pneumocystis carinii f. sp. hominis isolates in Japan.
    Author: Takahashi T, Kanda T, Iwamoto A.
    Journal: Res Commun Mol Pathol Pharmacol; 2002; 112(1-4):159-76. PubMed ID: 15080506.
    Abstract:
    This study examined gene polymorphisms in dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR) and cytochrome b of Pneumocystis carinii isolated from 34 patients with P. carinii pneumonia (PCP) in Japan. Four amino acid substitutions (Thr55Ala, Pro57Ser, His60Gln and Glu169Gly) in DHPS, 2 mutations (Ala67Val and Cys166Tyr) in DHFR and 1 mutation (Leu280Phe) in cytochrome b were found in 9 (26.5%), 2 (5.9%) and 1 (2.9%) patient, respectively. No linkage of mutations in DHPS to those in DHFR or cytochrome b was observed. The patients whose isolates showed mutations in DHPS, DHFR and cytochrome b were not exposed to sulfonamides, DHFR inhibitors and atovaquone before they developed PCP, except for 2 patients. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates showed wild-type DHPS (n=6 [85.7%] versus n=3 [12.5%]; P=0.001). Our results suggest that DHPS mutations may contribute to failure of co-trimoxazole treatment for PCP.
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