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Master's Dissertation
DOI
https://doi.org/10.11606/D.87.2015.tde-03092015-125658
Document
Author
Full name
João Daniel Santos Fernandes
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Pascon, Renata Castiglioni (President)
Araujo, Welington Luiz de
Ishida, Kelly
Title in Portuguese
Avaliação dos genes TRP3 e TRP5 da via de biossíntese do triptofano no patógeno oportunista C. neoformans quanto a sua aplicabilidade como alvo de drogas antifúngicas.
Keywords in Portuguese
Cryptococcus neoformans
Antimicóticos
Inibidores de enzimas
Micologia
Microbiologia médica
Abstract in Portuguese
Criptococose é uma doença causada pelo fungo C. neoformans que têm grande importância atualmente, devido ao aumento da população imunocomprometida,. Além disso, existem poucas opções terapêuticas contra micoses profundas. Neste trabalho foi avaliado se a via de biossíntese do triptofano seria um bom alvo para o desenvolvimento de novos antifúngicos. Com o uso da tecnologia de RNA de interferência, concluiu-se que esta via de síntese é essencial para a sobrevivência desta levedura, sendo, portanto, um ótimo alvo. Ainda neste estudo, demonstrou-se que a letalidade decorre da baixa captação de triptofano pelas permeases de aminoácidos, as quais sofrem repressão catabólica pela fonte de nitrogênio e efeito negativo da temperatura. Foram testados dois inibidores específicos que atuam sobre a antranilato sintase e a triptofano sintase, duas enzimas cruciais para a conversão do corismato em triptofano. Ambos compostos causaram inibição do crescimento de C. neoformans e C. gattii.
Title in English
Evaluation of TRP3 and TRP5 tryptophan biosynthetic pathway genes in the opportunistic pathogen Cryptococcus neofarmans and its applicability as a target for antifungal drugs.
Keywords in English
Cryptococcus neoformans
Antimycotics
Enzyme inhibitors
Medical microbiology
Mycology
Abstract in English
Cryptococcosis is a disease caused by C. neoformans, currently of great importance due to the increase in immunocompromised population. Furthermore, there are few therapeutic options for treating this disease. This study evaluated the tryptophan biosynthetic pathway as a possible target for the antifungal development. By using RNA interference technology we concluded that this metabolic pathway is essential for the survival of this yeast, and, therefore, it is a good target. In the same study, it was demonstrated that lethality results from the low uptake of the tryptophan amino acid by permeases, which undergo nitrogen catabolite repression and negative effect of temperature. Two specific inhibitors acting on the anthranilate synthase and tryptophan synthase, two key enzymes for the conversion of chorismate into tryptophan were tested. Both compounds caused growth inhibition of C. neoformans and C. gattii.
 
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Publishing Date
2015-09-18
 
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