Highly active antiretroviral therapy (HAART), that includes human immunodeficiency virus (HIV) protease inhibitors (PIs), has been remarkably efficacious including against some opportunistic infections. In this report we investigated the effect(s) of the PI indinavir on protease activity by Cryptococcus neoformans, an opportunistic fungal pathogen responsible for recurrent meningoencephalitis in AIDS patients. Indinavir was also tested for potential effects on other parameters, such as fungal viability, growth ability and susceptibility to immune effector cells. It was found that indinavir impaired cryptococcal protease activity in a time- and dose-dependent fashion. The phenomenon was similarly detectable in ATCC/laboratory strains and clinical isolates. C neoformans growth rate was also significantly reduced upon exposure to indinavir, while fungal viability was not affected and mitochondrial toxicity not detected. Furthermore, as assessed by an in vitro infection model, indinavir significantly and consistently augmented C neoformans susceptibility to microglial cell-mediated phagocytosis and killing. Overall, by providing the first evidence that indinavir directly affects C neoformans, these data add new in vitro insights on the wide-spectrum efficacy of PIs, further arguing for the clinical relevance of HAART against opportunistic infections in AIDS. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

Highly active antiretroviral therapy (HAART), that includes human immunodeficiency virus (HIV) protease inhibitors (PIs), has been remarkably efficacious including against some opportunistic infections. In this report we investigated the effect(s) of the PI indinavir on protease activity by Cryptococcus neoformans, an opportunistic fungal pathogen responsible for recurrent meningoencephalitis in AIDS patients. Indinavir was also tested for potential effects on other parameters, such as fungal viability, growth ability and susceptibility to immune effector cells. It was found that indinavir impaired cryptococcal protease activity in a time- and dose-dependent fashion. The phenomenon was similarly detectable in ATCC/laboratory strains and clinical isolates. C. neoformans growth rate was also significantly reduced upon exposure to indinavir, while fungal viability was not affected and mitochondrial toxicity not detected. Furthermore, as assessed by an in vitro infection model, indinavir significantly and consistently augmented C. neoformans susceptibility to microglial cell-mediated phagocytosis and killing. Overall, by providing the first evidence that indinavir directly affects C. neoformans, these data add new in vitro insights on the wide-spectrum efficacy of PIs, further arguing for the clinical relevance of HAART against opportunistic infections in AIDS.

The human immunodeficiency virus (HIV) protease inhibitor indinavir directly affects the opportunistic fungal pathogen Cryptococcus neoformans / Blasi, Elisabetta; Colombari, Bruna; Orsi, Carlotta Francesca; Pinti, Marcello; Troiano, L.; Cossarizza, Andrea; Esposito, Roberto; Peppoloni, Samuele; Mussini, Cristina; Neglia, Rachele Giovanna. - In: FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY. - ISSN 0928-8244. - STAMPA. - 42:(2004), pp. 187-195. [10.1016/j.femsim.2004.05.001]

The human immunodeficiency virus (HIV) protease inhibitor indinavir directly affects the opportunistic fungal pathogen Cryptococcus neoformans

BLASI, Elisabetta;COLOMBARI, Bruna;ORSI, Carlotta Francesca;PINTI, Marcello;COSSARIZZA, Andrea;ESPOSITO, Roberto;PEPPOLONI, Samuele;MUSSINI, Cristina;NEGLIA, Rachele Giovanna
2004

Abstract

Highly active antiretroviral therapy (HAART), that includes human immunodeficiency virus (HIV) protease inhibitors (PIs), has been remarkably efficacious including against some opportunistic infections. In this report we investigated the effect(s) of the PI indinavir on protease activity by Cryptococcus neoformans, an opportunistic fungal pathogen responsible for recurrent meningoencephalitis in AIDS patients. Indinavir was also tested for potential effects on other parameters, such as fungal viability, growth ability and susceptibility to immune effector cells. It was found that indinavir impaired cryptococcal protease activity in a time- and dose-dependent fashion. The phenomenon was similarly detectable in ATCC/laboratory strains and clinical isolates. C neoformans growth rate was also significantly reduced upon exposure to indinavir, while fungal viability was not affected and mitochondrial toxicity not detected. Furthermore, as assessed by an in vitro infection model, indinavir significantly and consistently augmented C neoformans susceptibility to microglial cell-mediated phagocytosis and killing. Overall, by providing the first evidence that indinavir directly affects C neoformans, these data add new in vitro insights on the wide-spectrum efficacy of PIs, further arguing for the clinical relevance of HAART against opportunistic infections in AIDS. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.
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The human immunodeficiency virus (HIV) protease inhibitor indinavir directly affects the opportunistic fungal pathogen Cryptococcus neoformans / Blasi, Elisabetta; Colombari, Bruna; Orsi, Carlotta Francesca; Pinti, Marcello; Troiano, L.; Cossarizza, Andrea; Esposito, Roberto; Peppoloni, Samuele; Mussini, Cristina; Neglia, Rachele Giovanna. - In: FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY. - ISSN 0928-8244. - STAMPA. - 42:(2004), pp. 187-195. [10.1016/j.femsim.2004.05.001]
Blasi, Elisabetta; Colombari, Bruna; Orsi, Carlotta Francesca; Pinti, Marcello; Troiano, L.; Cossarizza, Andrea; Esposito, Roberto; Peppoloni, Samuele; Mussini, Cristina; Neglia, Rachele Giovanna
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/310463
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