Portal de investigação
Genomic evolution towards azole resistance in Candida glabrata clinical isolates unveils the importance of CgHxt4/6/7 in azole accumulation
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Galocha, M
- Viana, R
- Pais, P
- Silva-Dias, A
- Cavalheiro, M
- Van Ende, M
- Souza, CS
- Costa, C
- Branco, J
- Soares, CM
- Van Dijck, P
- Teixeira, MC
Unidades de investigação
Abstract
The increasing prevalence of candidosis caused by Candida glabrata is related to its ability to acquire azole resistance. Although azole resistance mechanisms are well known, the mechanisms for azole import into fungal cells have remained obscure. In this work, we have characterized two hexose transporters in C. glabrata and further investigate their role as potential azole importers. Three azole susceptible C. glabrata clinical isolates were evolved towards azole resistance and the acquired resistance phenotype was found to be independent of CgPDR1 or CgERG11 mutations. Through whole-genome sequencing, CgHXT4/6/7 was found to be mutated in the three evolved strains, when compared to their susceptible parents. CgHxt4/6/7 and the 96% identical CgHxt6/7 were found to confer azole susceptibility and increase azole accumulation in C. glabrata cells, strikingly rescuing the susceptibility phenotype imposed by CgPDR1 deletion, while the identified loss-of-function mutation in CgHXT4/6/7, leads to increased azole resistance. In silico docking analysis shows that azoles display a strong predicted affinity for the glucose binding site of CgHxt4/6/7. Altogether, we hypothesize that hexose transporters, such as CgHxt4/6/7 and CgHxt6/7, may constitute a family of azole importers, involved in clinical drug resistance in fungal pathogens, and constituting promising targets for improved antifungal therapy. Mutations in the hexose transporter, CgHXT4/6/7, contribute to increased antifungal (azole) resistance in the fungal pathogen, Candida glabrata, potentially by influencing azole accumulation.
Dados da publicação
- ISSN/ISSNe:
- 2399-3642, 2399-3642
- Tipo:
- Article
- Páginas:
- -
- Link para outro recurso:
- www.scopus.com
Communications Biology Springer Nature
Citações Recebidas na Web of Science: 2
Citações Recebidas na Scopus: 2
Documentos
- Não há documentos
Filiações
Keywords
- PLEIOTROPIC DRUG-RESISTANCE; TRANSPORTERS; EXPRESSION; MECHANISMS; UPDATE; SYSTEM
Financiamento
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Citar a publicação
Galocha M,Viana R,Pais P,Silva A,Cavalheiro M,Miranda IM,Van M,Souza CS,Costa C,Branco J,Soares CM,Van P,Rodrigues AG,Teixeira MC. Genomic evolution towards azole resistance in <i>Candida glabrata</i> clinical isolates unveils the importance of CgHxt4/6/7 in azole accumulation. Commun. Biolog. 2022. 5. (1):1118. IF:5,900. (1).
