Inhibition of Pneumocystis carinii dihydropteroate synthetase by sulfa drugs.

نویسندگان

  • S Merali
  • Y Zhang
  • D Sloan
  • S Meshnick
چکیده

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 activities of 450 and 14 U/mg, respectively. A comparison of the effects of five sulfa drugs on P. carinii DHPS activity revealed that dapsone is the most potent of these drugs.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

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...

متن کامل

Absence of mutations associated with sulfa resistance in Pneumocystis carinii dihydropteroate synthase gene from non-human primates.

The dihydropteroate synthase (DHPS) gene from Pneumocystis carinii isolated from non-human primates was amplified using a polymerase chain reaction (PCR) and sequenced to analyse point mutations associated with sulfa resistance. P. carinii DHPS gene amplification was obtained from eight lung samples from five New World primate species and one Old World primate species. None of the animals had b...

متن کامل

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.

متن کامل

Relationship between mutations in dihydropteroate synthase of Pneumocystis carinii f. sp. hominis isolates in Japan and resistance to sulfonamide therapy.

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneumocystis carinii f. sp. hominis (P. carinii) strains isolated from 24 patients with P. carinii pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients. The underlying diseases for these six patients were human immunodeficiency virus type 1 inf...

متن کامل

Distribution of DHPS Mutations Among ITS Subtypes of P. carinii

Sulfa drugs are widely used in the prophylaxis and treatment of Pneumocystis carinii pneumonia. Co-trimoxasole, the first-line agent, is a combination of sulfamethoxazole plus trimethoprim but functions as sulfa monotherapy since trimethoprim appears to be inactive. Dapsone, a sulfone, is a commonly used second line agent. Both sulfamethoxazole and dapsone act by binding to the dihydropteroate ...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Antimicrobial agents and chemotherapy

دوره 34 6  شماره 

صفحات  -

تاریخ انتشار 1990