The Molecular Basis of Sulfonamide Resistance inToxoplasma gondiiand Implications for the Clinical Management of Toxoplasmosis
| Autor: | Tanya V. Aspinall, Paul F. G. Sims, David H. M. Joynson, John E. Hyde, Edward Guy |
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| Rok vydání: | 2002 |
| Předmět: |
Drug Resistance
DHPS Drug resistance law.invention Microbiology Sulfadiazine law parasitic diseases Escherichia coli medicine Animals Humans Immunology and Allergy Gene Polymerase chain reaction Dihydropteroate Synthase Sulfonamides biology Toxoplasma gondii Sequence Analysis DNA biology.organism_classification medicine.disease Virology Toxoplasmosis Tetrahydrofolate Dehydrogenase Infectious Diseases Coccidiostats Dihydropteroate synthase Toxoplasma medicine.drug |
| Zdroj: | The Journal of Infectious Diseases. 185:1637-1643 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1086/340577 |
| Popis: | Polymerase chain reaction amplification and DNA sequencing of the Toxoplasma gondii dihydropteroate synthase gene (dhps) identified 4 alleles among parasite populations from 32 cases of human toxoplasmosis. Heterologous expression and enzyme assay reveal that 3 of these alleles encode sulfadiazine (Sdz)-sensitive enzymes. The fourth, generating a highly Sdz-resistant enzyme, differs from 1 of the other 3 at only a single residue (407) of DHPS. Of interest, a fifth allele, found in a laboratory-induced Sdz-resistant line, also differs from another of these 3 drug-sensitive forms by the same single mutation that affects residue 407 of DHPS. Significantly, residues corresponding to DHPS-407 are implicated in sulfonamide resistance in other microorganisms. The human-derived allelic form encoding the Sdz-resistant enzyme was found in T. gondii associated with a fatal infection, and its presence within clinical material may have implications for sulfonamide use, particularly in cases of toxoplasmosis in which the initial response to drug treatment is poor. |
| Databáze: | OpenAIRE |
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