XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:69-1

Poster (Painel)

69-1	Transcriptional response of Paracoccidioides brasiliensis during exposition to oenothein B
Authors:	Patricia Fernanda Zambuzzi Carvalho (UFG - Universidade Federal de Goiás) ; Clayton Luiz Borges (UFG - Universidade Federal de Goiás) ; Pedro Henrique Ferri (UFG - Universidade Federal de Goiás) ; Suzana da Costa Santos (UFG - Universidade Federal de Goiás) ; Celia Maria de Almeida Soares (UFG - Universidade Federal de Goiás) ; Maristela Pereira (UFG - Universidade Federal de Goiás)

Abstract

Paracoccidioidomycosis (PCM) is an important endemic mycosis in Latin America, caused by the fungus Paracoccidioides brasiliensis. The treatment of PCM is long and the resistance to antimicrobial drugs interferes with therapeutic efficacy. Thus, it is necessary to discover and develop new antifungal agents. Plants compounds have a great structural diversity; many of them are models for the synthesis of a huge number of drugs. In this way, we have investigated the action of the oenothein B, compound purified from leaves of Eugenia uniflora, on P. brasiliensis. Oenothein B interferes with the cell morphology of P. brasiliensis, probably by inhibiting the transcription of 1,3-&Betaβ-glucan synthase gene (PbFKS1), which is involved in the cell wall synthesis. Aiming obtain information about the global mechanism of action of oenothein B on fungus, we investigated the transcriptional profile of P. brasiliensis exposed to oenothein B by Representational Difference Analysis (RDA). P. brasiliensis yeast cells were grown on minimum medium in the presence and absence of oenothein B for 90 and 180 min. After extraction of total RNA, the cDNA was obtained and used to RDA experiments aiming to identify ESTs up and down regulated. ESTs sequences were clustering using the CAP3 program. By using BLAT2GO program, the ESTs were classified in agreement with the functions. The analyses indicated the presence of transcripts with functions related to cell wall, membrane, stress, transcription factors and hypothetic proteins. The results obtained by RDA and bioinformatics were confirmed by real time PCR. In addition, the amount of polysaccharides from cell wall was measured since oenothein B inhibits transcription of PbFKS1. Analysis identified decreased of &Betaβ-1-3-glucan and increased of N-acetylglucosamine residues. The synergism between oenothein B and amphotericin B, itraconazole, sulfamethoxazole and sulfametoxazol/trimetoprim was also evaluated. The elucidation of the action mode of oenothein B will facilitate the design of related compounds with enhanced pharmacological profiles.਀䘀椀渀愀渀挀椀愀氀匀甀瀀瀀漀爀琀㨀䌀䄀倀䔀匀Ⰰ 䌀一倀焀Ⰰ 䤀䘀匀Ⰰ 䘀唀一䄀倀䔀⸀

Keyword: Antifungal, Oenothein B, Paracoccidioides brasiliensis, Transcriptome

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