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Antimicrobial Agents and Chemotherapy, June 2005, p. 2362-2366, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2362-2366.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibitory Activity of Human Immunodeficiency Virus Aspartyl Protease Inhibitors against Encephalitozoon intestinalis Evaluated by Cell Culture-Quantitative PCR Assay

Jean Menotti,1,4* Maud Santillana-Hayat,4 Bruno Cassinat,2 Claudine Sarfati,1,4 Francis Derouin,1,4 and Jean-Michel Molina3,4

Laboratory of Parasitology-Mycology,1 Department of Nuclear Medicine,2 Department of Infectious Diseases, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris,3 EA-3520, Faculté de Médecine Lariboisière-Saint-Louis, Université Paris 7, Paris, France4

Received 1 October 2004/ Returned for modification 25 October 2004/ Accepted 11 February 2005

Immune reconstitution might not be the only factor contributing to the low prevalence of microsporidiosis in human immunodeficiency virus (HIV)-infected patients treated with protease inhibitors, as these drugs may exert a direct inhibitory effect against fungi and protozoa. In this study, we developed a cell culture-quantitative PCR assay to quantify Encephalitozoon intestinalis growth in U-373-MG human glioblastoma cells and used this assay to evaluate the activities of six HIV aspartyl protease inhibitors against E. intestinalis. A real-time quantitative PCR assay targeted the E. intestinalis small-subunit rRNA gene. HIV aspartyl protease inhibitors were tested over serial concentrations ranging from 0.2 to 10 mg/liter, with albendazole used as a control. Ritonavir, lopinavir, and saquinavir were able to inhibit E. intestinalis growth, with 50% inhibitory concentrations of 1.5, 2.2, and 4.6 mg/liter, respectively, whereas amprenavir, indinavir, and nelfinavir had no inhibitory effect. Pepstatin A, a reference aspartyl protease inhibitor, could also inhibit E. intestinalis growth, suggesting that HIV protease inhibitors may act through the inhibition of an E. intestinalis-encoded aspartyl protease. These results showed that some HIV protease inhibitors can inhibit E. intestinalis growth at concentrations that are achievable in vivo and that the real-time quantitative PCR assay that we used is a valuable tool for the in vitro assessment of the activities of drugs against E. intestinalis.

* 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: jean.menotti{at}sls.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, June 2005, p. 2362-2366, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2362-2366.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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