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Aspartic Proteolytic Inhibitors Induce Cellular and Biochemical Alterations in Fungal Cells

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Book cover Proteases in Health and Disease

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 7))

Abstract

Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Diagnosis and treatment of fungal infections remain a challenge in medicine despite recent major advances. The search for novel pharmacological compounds with antifungal action is a real requirement. Taking it into consideration, research groups have investigated the effects of aspartic peptidase inhibitors (PIs) on the development of human fungal pathogens such as Candida spp, mainly Candida albicans and Candida parapsilosis, Cryptococcus neoformans, Pneumocystis jiroveci and Fonsecaea pedrosoi, based on the following premises: (1) this class of hydrolytic enzymes performs multiple relevant roles in pathophysiological events associated to the fungal infections and (2) the introduction of human immunodeficiency virus (HIV) PIs in the clinical arena drastically reduced the opportunistic infections caused by fungi in this population. As expected, the blockage of one of these physiological/pathological processes should help in containing the fungal infection. Corroborating this hypothesis, both in vitro and in vivo studies have reported that classical aspartic PIs (e.g., pepstatin A) as well as HIV PIs (e.g., nelfinavir, saquinavir, ritonavir, indinavir, amprenavir, lopinavir and tipranavir) have induced several cellular and biochemical alterations on fungal cells. Some of the metabolic perturbations are extremely drastic to the fungal cells, which culminate in arresting nutrition, growth, proliferation, differentiation, adhesion, invasion and dissemination. In the present chapter, we will describe the beneficial effects of aspartic PIs against some human fungal pathogens, reporting in details their mechanisms capable in disturbing the fungal homeostasis.

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Acknowledgements

This study was supported by grants from the Brazilian Agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa no Estado do Rio de Janeiro (FAPERJ), Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho de Ensino e Pesquisa para Graduados da Universidade Federal do Rio de Janeiro (CEPG-UFRJ), Fundação Oswaldo Cruz (FIOCRUZ), Fundação de Amparo à Ciência do Estado de Pernambuco (FACEPE), NanoBiotec-BR and INCT-INAMI. André L.S. Santos was supported by CNPq and FAPERJ fellowships.

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Authors and Affiliations

  1. Laboratório de Investigação de Peptidases, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Bloco E-subsolo, Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    André L. S. Santos & Lys A. Braga-Silva

  2. Programa de Pós-Graduação em Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    André L. S. Santos & Lys A. Braga-Silva

  3. Departamento de Ciências Básicas, Pólo Universitário de Nova Friburgo, Universidade Federal Fluminense (UFF), Nova Friburgo, Rio de Janeiro, Brazil

    Bianca A. Silva

  4. Laboratório de Investigação de Peptidases, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Bloco E-subsolo, Centro de Ciências da Saúde (CCS), Universidade Federal Fluminense (UFF), Nova Friburgo, Rio de Janeiro, Brazil

    Vanila F. Palmeira, Roberta S. Valle & Érika A. Abi-chacra

  5. Laboratório de Modelagem de Biomateriais, Departamento de Química Fundamental, Universidade Federal de Pernambuco (UFPE), Pernambuco, Brazil

    Vanessa S. Oliveira & Roberto D. Lins

  6. Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil

    Lucimar F. Kneipp

  7. Departamento de Biologia Celular e Molecular, Intituto de Biologia, Universidade Federal Fluminense (UFF), Niterói, Rio de Janeiro, Brazil

    Cátia L. Sodré

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  1. André L. S. Santos
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  2. Lys A. Braga-Silva
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  3. Bianca A. Silva
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  7. Vanessa S. Oliveira
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  10. Cátia L. Sodré
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Correspondence to André L. S. Santos .

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Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Sciences, University of Manitoba, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

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Santos, A.L.S. et al. (2013). Aspartic Proteolytic Inhibitors Induce Cellular and Biochemical Alterations in Fungal Cells. In: Chakraborti, S., Dhalla, N. (eds) Proteases in Health and Disease. Advances in Biochemistry in Health and Disease, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9233-7_7

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