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Protease expression by microorganisms and its relevance to crucial physiological/pathological events

World Journal of Biological Chemistry 2011年第3期2卷 48-58页

作者： AndréLuis Souza dos Santos Laboratory of Multidisciplinary Studies on Microbial Biochemistry Department of General MicrobiologyInstitute of Microbiology Prof.Paulo de GóesFederal University of Rio de JaneiroRio de JaneiroRJ 21941-902 Brazil

The treatment of infections caused by fungi and trypanosomatids is difficult due to the eukaryotic nature of these microbial cells,which are similar in several biochemical and genetic aspects to host *** this scenario,very few antifungal and anti-trypanosomatidal agents are in clinical use and,therefore,therapy is limited by drug safety considerations and their narrow spectrum of activity,efficacy and resistance. The search for new bioactive agents against fungi and trypanosomatids has been expanded because progress in biochemistry and molecular biology has led to a better understanding of important and essential pathways in these microorganisms including nutrition,growth, proliferation,signaling,differentiation and *** this context,proteolytic enzymes produced by these eukaryotic microorganisms are appointed and,in some cases,proven to be excellent targets for searching novel natural and/or synthetic pharmacological compounds,in order to cure or prevent invasive fungal/trypanosomatid *** this task in mind,our research group and others have focused on aspartic-type proteases,since the activity of this class of hydrolytic enzymes is directly implicated in several facets of basic biological processes of both fungal and trypanosomatid cells as well as due to the participation in numerous events of interaction between these microorganisms and host *** the present paper,a concise revision of the beneficial effects of aspartic protease inhibitors,with emphasis on the aspartic protease inhibitors used in the anti-human immunodeficiency virus therapy,will be presented and discussed using our experience with the following microbial models:the yeast Candida albicans,the filamentous fungus Fonsecaea pedrosoi and the protozoan trypanosomatid Leishmania amazonensis.

关键词： Protease Aspartic protease inhibitors trypanosomatids Fungi Cell biology Virulence Chemotherapy

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