This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meneceur, P.
Right arrow Articles by Derouin, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meneceur, P.
Right arrow Articles by Derouin, F.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2008, p. 1269-1277, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01203-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

In Vitro Susceptibility of Various Genotypic Strains of Toxoplasma gondii to Pyrimethamine, Sulfadiazine, and Atovaquone{triangledown}

Pascale Meneceur,1,{dagger} Marie-Anne Bouldouyre,1,{dagger} Dominique Aubert,3 Isabelle Villena,3 Jean Menotti,1,2 Virginie Sauvage,3 Jean-François Garin,1,2 and Francis Derouin1,2*

Laboratory of Parasitology (EA 3520), University Denis Diderot, 15 Rue de l'École de Médecine, 75250 Paris Cedex 06, France,1 Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 1, Avenue Claude Vellefaux, 75010 Paris, France,2 Laboratory of Parasitology (EA 3800), and Biological Resource Centre Toxoplasma, University of Reims Champagne-Ardennes and Hôpital Maison-Blanche, 45 Rue Cognacq-Jay, 51092 Reims Cedex, France3

Received 12 September 2007/ Returned for modification 29 November 2007/ Accepted 12 January 2008

Sulfadiazine, pyrimethamine, and atovaquone are widely used for the treatment of severe toxoplasmosis. Their in vitro activities have been almost exclusively demonstrated on laboratory strains belonging to genotype I. We determined the in vitro activities of these drugs against 17 strains of Toxoplasma gondii belonging to various genotypes and examined the correlations among 50% inhibitory concentrations (IC50s), growth kinetics, strain genotypes, and mutations on drug target genes. Growth kinetics were determined in THP-1 cell cultures using real-time PCR. IC50s were determined in MRC-5 cell cultures using a T. gondii-specific enzyme-linked immunosorbent assay performed on cultures. Mutations in dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and cytochrome b genes were determined by sequencing. Pyrimethamine IC50s ranged between 0.07 and 0.39 mg/liter, with no correlation with the strain genotype but a significant correlation with growth kinetics. Several mutations found on the DHFR gene were not linked to lower susceptibility. Atovaquone IC50s were in a narrow range of concentrations (mean, 0.06 ± 0.02 mg/liter); no mutation was found on the cytochrome b gene. IC50s for sulfadiazine ranged between 3 and 18.9 mg/liter for 13 strains and were >50 mg/liter for three strains. High IC50s were not correlated to strain genotypes or growth kinetics. A new mutation of the DHPS gene was demonstrated in one of these strains. In conclusion, we found variability in the susceptibilities of T. gondii strains to pyrimethamine and atovaquone, with no evidence of drug resistance. A higher variability was found for sulfadiazine, with a possible resistance of three strains. No relationship was found between drug susceptibility and strain genotype.

* Corresponding author. Mailing address: Laboratoire de Parasitologie/Mycologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France. Phone: (33) 1 42 49 95 03. Fax: (33) 1 42 49 48 03. E-mail: francis.derouin{at}sls.aphp.fr

{triangledown} Published ahead of print on 22 January 2008.

{dagger} P.M. and M.-A.B. contributed equally to the work.

Antimicrobial Agents and Chemotherapy, April 2008, p. 1269-1277, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01203-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Persson, C. M., Lambert, H., Vutova, P. P., Dellacasa-Lindberg, I., Nederby, J., Yagita, H., Ljunggren, H.-G., Grandien, A., Barragan, A., Chambers, B. J. (2009). Transmission of Toxoplasma gondii from Infected Dendritic Cells to Natural Killer Cells. Infect. Immun. 77: 970-976 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»