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Transcriptional profile of Paracoccidioides spp. in response to itraconazole.
BMC Genomics. 2014 Apr 01; 15:254.BG

Abstract

BACKGROUND

Itraconazole is currently used to treat paracoccidioidomycosis. The mechanism of action of azoles has been elucidated in some fungi, although little is known regarding its mechanism of action in Paracoccidioides spp. The present work focused on identification of regulated transcripts using representational difference analysis of Paracoccidioides spp. yeast cells treated with itraconazole for 1 and 2 h.

RESULTS

Paracoccidioides Pb01 genes up-regulated by itraconazole included genes involved in cellular transport, metabolism/energy, transcription, cell rescue, defense and virulence. ERG11, ERG6, ERG3, ERG5 and ERG25 were up-regulated at multiple time points. In vivo infection experiments in mice corroborated the in vitro results. Ergosterol levels and distribution were evaluated in Paracoccidioides Pb18 yeast cells, and the results demonstrate that both factors were changed in the fungus treated with itraconazole.

CONCLUSION

To our knowledge, this is the first transcriptional analysis of Paracoccidioides spp. exposed to a triazole drug. Here acetyl seems to be intensively produced from different metabolic pathways to produce ergosterol by the action of ergosterol synthesis related enzymes, which were also affected in other fungi. Among the genes affected, we identified genes in common with other fungi, as well as genes unique to Paracoccidioides Pb01. Those genes could be considered target to new drugs. Voltage-gated Ca2+ alpha subunit (CAV), Tetracycline resistance protein (TETA) and Hemolisyn-iii channel protein (HLYiii) were found only here and a probably involvement with resistance to itraconazole could be investigated in the future. However our findings do not permit inference to current clinical practice.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableDepartamento de Bioquímica e Biologia Molecular, Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, C,P, 131, 74001-970 Goiânia, GO, Brazil. maristelaufg@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24690401

Citation

da Silva Neto, Benedito Rodrigues, et al. "Transcriptional Profile of Paracoccidioides Spp. in Response to Itraconazole." BMC Genomics, vol. 15, 2014, p. 254.
da Silva Neto BR, Carvalho PF, Bailão AM, et al. Transcriptional profile of Paracoccidioides spp. in response to itraconazole. BMC Genomics. 2014;15:254.
da Silva Neto, B. R., Carvalho, P. F., Bailão, A. M., Martins, W. S., Soares, C. M., & Pereira, M. (2014). Transcriptional profile of Paracoccidioides spp. in response to itraconazole. BMC Genomics, 15, 254. https://doi.org/10.1186/1471-2164-15-254
da Silva Neto BR, et al. Transcriptional Profile of Paracoccidioides Spp. in Response to Itraconazole. BMC Genomics. 2014 Apr 1;15:254. PubMed PMID: 24690401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcriptional profile of Paracoccidioides spp. in response to itraconazole. AU - da Silva Neto,Benedito Rodrigues, AU - Carvalho,Patrícia Fernanda Zambuzzi, AU - Bailão,Alexandre Melo, AU - Martins,Wellington Santos, AU - Soares,Célia Maria de Almeida, AU - Pereira,Maristela, Y1 - 2014/04/01/ PY - 2013/07/19/received PY - 2014/03/26/accepted PY - 2014/4/3/entrez PY - 2014/4/3/pubmed PY - 2014/11/19/medline SP - 254 EP - 254 JF - BMC genomics JO - BMC Genomics VL - 15 N2 - BACKGROUND: Itraconazole is currently used to treat paracoccidioidomycosis. The mechanism of action of azoles has been elucidated in some fungi, although little is known regarding its mechanism of action in Paracoccidioides spp. The present work focused on identification of regulated transcripts using representational difference analysis of Paracoccidioides spp. yeast cells treated with itraconazole for 1 and 2 h. RESULTS: Paracoccidioides Pb01 genes up-regulated by itraconazole included genes involved in cellular transport, metabolism/energy, transcription, cell rescue, defense and virulence. ERG11, ERG6, ERG3, ERG5 and ERG25 were up-regulated at multiple time points. In vivo infection experiments in mice corroborated the in vitro results. Ergosterol levels and distribution were evaluated in Paracoccidioides Pb18 yeast cells, and the results demonstrate that both factors were changed in the fungus treated with itraconazole. CONCLUSION: To our knowledge, this is the first transcriptional analysis of Paracoccidioides spp. exposed to a triazole drug. Here acetyl seems to be intensively produced from different metabolic pathways to produce ergosterol by the action of ergosterol synthesis related enzymes, which were also affected in other fungi. Among the genes affected, we identified genes in common with other fungi, as well as genes unique to Paracoccidioides Pb01. Those genes could be considered target to new drugs. Voltage-gated Ca2+ alpha subunit (CAV), Tetracycline resistance protein (TETA) and Hemolisyn-iii channel protein (HLYiii) were found only here and a probably involvement with resistance to itraconazole could be investigated in the future. However our findings do not permit inference to current clinical practice. SN - 1471-2164 UR - https://www.unboundmedicine.com/medline/citation/24690401/Transcriptional_profile_of_Paracoccidioides_spp__in_response_to_itraconazole_ L2 - https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-15-254 DB - PRIME DP - Unbound Medicine ER -