The molecular basis of sulfonamide resistance in Toxoplasma gondii and implications for the clinical management of toxoplasmosis.

Autor: Aspinall TV; Department of Biomolecular Sciences, Institute of Science and Technology, University of Manchester, Sackville Street, Manchester M60 1QD, UK. tpashly@umist.ac.uk, Joynson DH, Guy E, Hyde JE, Sims PF
Jazyk: angličtina
Zdroj: The Journal of infectious diseases [J Infect Dis] 2002 Jun 01; Vol. 185 (11), pp. 1637-43. Date of Electronic Publication: 2002 May 17.
DOI: 10.1086/340577
Abstrakt: 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: MEDLINE