Análise da região promotora dos genes de proteínas relacionadas à biossíntese de isoprenos, esteróis e metabolismo lipídico no Paracoccidioides sp.
Arquivos
Data
2021-02-24
Autores
Ferreira, Elis Cecília Castro 
Orientadores
Campos, Cláudia Barbosa Ladeira
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O Paracoccidioides brasiliensis e Paracoccidioides lutzii são fungos
patogênicos termodimórfico, agentes etiológico da micose sistêmica
paracoccidioidomicose (PCM), uma doença endêmica no Brasil que acomete
principalmente pessoas que exercem atividades agrícolas. O tratamento é
demorado e muitos abandonam a terapia antes de serem de fato reestabelecidos.
A calcineurina, uma fosfatase de serina e treonina ativada por Ca²+ e calmodulina,
é importante no processo de morfogênese dos fungos, como também na
proliferação, sobrevivência e patogenicidade. Um estudo proteômico realizado pelo
grupo com objetivo de investigar o papel da calcineurina na dinâmica celular de P.
brasilienses identificou que leveduras desse fungo cultivado na presença de um
inibidor da calcineurina, ciclosporina A, as enzimas Isopentenil-difosfato deltaisomerase, HMG-CoA sintase, e Difosfomevalonato Decarboxilase pertencentes a
via do mevalonato e metabolismo lipídico apresentavam seus níveis reduzidos
devido a inibição da calcineurina. Nesse sentido, tendo em vista que os fatores de
transcrição são elementos regulatórios que estão relacionados com o aumento ou
diminuição da expressão de certas proteínas o objetivo deste trabalho foi
caracterizar os genes das proteínas acima citadas por análises de bioinformática e
estudar os possíveis fatores de transcrição que se associam a região promotora
destes genes, assim investigar e propor possibilidades quanto a dinâmica celular
nos quais esses elementos regulatórios podem estar envolvidos no gênero
Paracoccidioides sp. tendo em vista a inibição da calcineurina e a PCM. Desse
modo, foram encontrados fatores gerais como GCN4,GA-BF, NIT2 e RC2 sendo
elementos gerais associados a tais proteínas. O fator MAC1 e MATα1 foi associado
tendo em vista a regulação da HMG-CoA sintase. E os fatores STE12, CCBF, SWI4
e SWI6 foram associados tendo em vista a regulação da IPP isomerase e os
elementos que possivelmente regulam a difosfomevalonato descarboxilase foram
os mesmos elementos gerais associados. Sendo uma perspectiva futura verificar
experimentalmente se tais fatores são de fato associados a tais genes no
Paracoccidioides sp.
Paracoccidioides brasiliensis and Paracoccidioides lutzii are thermodimorphic pathogenic fungi, etiological agents of systemic mycosis paracoccidioidomycosis (PCM), an endemic disease in Brazil that mainly affects people who perform agricultural activities. Treatment is time-consuming and many abandon therapy before they are actually restored. Calcineurin, a serine and threonine phosphatase activated by Ca2 + and calmodulin, is important in the process of fungal morphogenesis, as well as in proliferation, survival and pathogenicity. A proteomic study carried out by the group in order to investigate the role of calcineurin in the cell dynamics of P. brasilienses identified that yeasts of this fungus grown in the presence of a calcineurin inhibitor, cyclosporine A, the enzymes Isopentenyl-diphosphate delta-isomerase, HMG-CoA synthase, and Diphosphomevalonate Decarboxylase, belonging to the mevalonate pathway and lipid metabolism, had their levels reduced in front of the inhibition of calcineurin. In this sense, considering that the transcription factors are regulatory elements that are related to the increase or decrease in the expression of proteins, the objective of this work was to characterize the genes of the proteins mentioned above by bioinformatics analysis and to study the possible transcription factors which are associated with the promoter region of these genes, thus investigate and propose possibilities regarding the cell dynamics in which these regulatory elements may be involved in the genus Paracoccidioides sp. in view of the inhibition of calcineurin and in the context of PCM. In this sense, general factors such as GCN4, GA-BF, NIT2 and RC2 were found being general elements associated with such proteins. The MAC1 and MATα1 factor was associated with the regulation of HMG-CoA synthase. And the factors STE12, CCBF, SWI4 and SWI6 were associated in view of the regulation of IPP isomerase and the elements that possibly regulate diphosphomevalonate decarboxylase were the same general associated elements. It is a future perspective to verify experimentally whether such factors are in fact associated with such genes in Paracoccidioides sp.
Paracoccidioides brasiliensis and Paracoccidioides lutzii are thermodimorphic pathogenic fungi, etiological agents of systemic mycosis paracoccidioidomycosis (PCM), an endemic disease in Brazil that mainly affects people who perform agricultural activities. Treatment is time-consuming and many abandon therapy before they are actually restored. Calcineurin, a serine and threonine phosphatase activated by Ca2 + and calmodulin, is important in the process of fungal morphogenesis, as well as in proliferation, survival and pathogenicity. A proteomic study carried out by the group in order to investigate the role of calcineurin in the cell dynamics of P. brasilienses identified that yeasts of this fungus grown in the presence of a calcineurin inhibitor, cyclosporine A, the enzymes Isopentenyl-diphosphate delta-isomerase, HMG-CoA synthase, and Diphosphomevalonate Decarboxylase, belonging to the mevalonate pathway and lipid metabolism, had their levels reduced in front of the inhibition of calcineurin. In this sense, considering that the transcription factors are regulatory elements that are related to the increase or decrease in the expression of proteins, the objective of this work was to characterize the genes of the proteins mentioned above by bioinformatics analysis and to study the possible transcription factors which are associated with the promoter region of these genes, thus investigate and propose possibilities regarding the cell dynamics in which these regulatory elements may be involved in the genus Paracoccidioides sp. in view of the inhibition of calcineurin and in the context of PCM. In this sense, general factors such as GCN4, GA-BF, NIT2 and RC2 were found being general elements associated with such proteins. The MAC1 and MATα1 factor was associated with the regulation of HMG-CoA synthase. And the factors STE12, CCBF, SWI4 and SWI6 were associated in view of the regulation of IPP isomerase and the elements that possibly regulate diphosphomevalonate decarboxylase were the same general associated elements. It is a future perspective to verify experimentally whether such factors are in fact associated with such genes in Paracoccidioides sp.
Descrição
Citação
Ferreira, E. C.C; Análise da região promotora dos genes de proteínas relacionadas à biossíntese de isoprenos, esteróis e metabolismo lipídico no Paracoccidioides sp. Dissertação apresentada à Universidade Federal de São Paulo - Instituto de Ciência e Tecnologia, para obtenção do título de Bacharel em Biotecnologia, 2021.