Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs

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Inhibition of Pneumocystis carinii dihydropteroate synthetase by sulfa drugs.

A new reversed-phase high-pressure liquid chromatography assay procedure for dihydropteroate synthetase (DHPS) that involves the elution of the enzyme incubation solution with a series of three solvents of decreasing polarity (ammonium phosphate buffer, 10% methanol, and 50% methanol) was designed. By this procedure DHPS was detected in Escherichia coli and Pneumocystis carinii with specific ac...

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Evaluation of sulfa drugs against recombinant Pneumocystis carinii dihydropteroate synthetase and in vivo.

Sulfa drugs are potent and important anti-pneumocystis agents, but have a high incidence of adverse effects in AIDS patients. Although 15,000 sulfa drugs have been synthesized and dozens have been used in people, relatively few have been tested against P. carinii. In order to determine whether there are sulfa drugs which are better antipneumocystis agents than sulfamethoxazole and dapsone, we h...

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Sulfa Resistance and Dihydropteroate Synthase Mutants in Recurrent Pneumocystis carinii Pneumonia

Failure of sulfa or sulfone prophylaxis is associated with mutations in Pneumocystis carinii gene coding for dihydropteroate synthase (DHPS). The DHPS genotype was analyzed in AIDS patients who had two separate episodes of P. carinii pneumonia. The results suggest that DHPS mutations can be selected de novo within patients by the pressure of a sulfa or sulfone drug.

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Dihydropteroate Synthase Gene Mutations in Pneumocystis and Sulfa Resistance

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovec...

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Sulfa Use, Dihydropteroate Synthase Mutations, and Pneumocystis jirovecii Pneumonia

A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and sulfa treatment outcome. Selection criteria included study populations composed entirely of PCP patients and mutation or treatment outcome results for all patient...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 1995

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.39.8.1756