The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus

The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus

Autor Ferreira, MED Google Scholar
Colombo, A. L. Google Scholar
Paulsen, I Google Scholar
Ren, Q. Google Scholar
Wortman, J. Google Scholar
Huang, J. Google Scholar
Goldman, MHS Google Scholar
Goldman, G. H. Google Scholar
Instituição Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
TIGR
Resumo The continuous use of triazoles can result in the development of drug resistance. Azole-resistant clinical isolates, spontaneous and induced mutants of Aspergillus fumigatus have been documented. the azoles block the ergosterol biosynthesis pathway by inhibiting the enzyme 14-alpha-demethylase, product of the CYP51. Fungal azole resistance involves both amino acid changes in the target site that alter drug-target interactions and those that decrease net azole accumulation. the reduced intracellular accumulation has also been correlated with overexpression of multidrug resistance (MDR) efflux transporter genes of the ATP-binding cassette (ABC) and the major facilitator superfamily (MFS) classes. About 20 genes are involved in the A. fumigatus ergosterol biosynthesis pathway. There are several duplicated genes in this pathway. Interestingly, erg3 and erg11 showed two copies in A. fumigatus. in general, Aspergillus spp. have proportionally more MFS transporter encoding genes than Saccharomyces cerevisiae, S. pombe, and Neurospora crassa. the drug H+ (12 and 14 spanners) sub-families are also proportionally greater than in the other species. Although the numbers of ABC transporter encoding genes are comparable, again the Aspergillus spp. have more ABC transporters related to multidrug permease than the other fungal species.
Palavra-chave Aspergillus fumigatus
azoles
ergosterol
transporters
Idioma Inglês
Data de publicação 2005-05-01
Publicado em Medical Mycology. Abingdon: Taylor & Francis Ltd, v. 43, p. S313-S319, 2005.
ISSN 1369-3786 (Sherpa/Romeo, fator de impacto)
Publicador Taylor & Francis Ltd
Extensão S313-S319
Fonte http://dx.doi.org/10.1080/13693780400029114
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000230896300046
Endereço permanente http://repositorio.unifesp.br/handle/11600/28288

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