Open AccessThe human immunodeficiency virus (HIV) protease inhibitor indinavir directly affects the opportunistic fungal pathogen Cryptococcus neoformans
Author(s) -
Blasi Elisabetta,
Colombari Bruna,
Francesca Orsi Carlotta,
Pinti Marcello,
Troiano Leonarda,
Cossarizza Andrea,
Esposito Roberto,
Peppoloni Samuela,
Mussini Cristina,
Neglia Rachele
Publication year - 2004
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1016/j.femsim.2004.05.001
Subject(s) - indinavir , cryptococcus neoformans , microbiology and biotechnology , biology , virology , protease , cryptococcosis , protease inhibitor (pharmacology) , opportunistic infection , immunology , virus , viral disease , sida , viral load , enzyme , antiretroviral therapy , biochemistry
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.