MEM INST OSWALDO CRUZ, RIO DE JANEIRO, Vol. 113 | 2018
PAGES: DOI: 10.1590/0074-02760170484 Full paper
Characterisation of an ABC transporter of a resistant Candida glabrata clinical isolate

Debora Afonso Silva Rocha1, Leandro Figueira Reis de Sa1, Ana Carolina Cartagenes Pinto1, Maria de Lourdes Junqueira2, Emiliana Mandarano da Silva3, Ronaldo Mohana Borges3, Antonio Ferreira-Pereira1,+

1Universidade Federal do Rio de Janeiro, Instituto de Microbiologia Paulo de Goes, Laboratório de Bioquímica Microbiana, Rio de Janeiro, RJ, Brasil
2Universidade Federal de Juiz de Fora, Hospital Universitário, Juiz de Fora, MG, Brasil
3Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Genômica Estrutural, Rio de Janeiro, RJ, Brasil

Abstract

BACKGROUND Candida glabrata ranks second in epidemiological surveillance studies, and is considered one of the main human yeast pathogens. Treatment of Candida infections represents a contemporary public health problem due to the limited availability of an antifungal arsenal, toxicity effects and increasing cases of resistance. C. glabrata presents intrinsic fluconazole resistance and is a significant concern in clinical practice and in hospital environments.

OBJECTIVE The aim of this study was to characterise the azole resistance mechanism presented by a C. glabrata clinical isolate from a Brazilian university hospital.

METHODS Azole susceptibility assays, chemosensitisation, flow cytometry and mass spectrometry were performed.

FINDINGS Our study demonstrated extremely high resistance to all azoles tested: fluconazole, voriconazole, posaconazole and itraconazole. This isolate was chemosensitised by FK506, a classical inhibitor of ABC transporters related to azole resistance, and Rhodamine 6G extrusion was observed. A mass spectrometry assay confirmed the ABC protein identification suggesting the probable role of efflux pumps in this resistance phenotype.

MAIN CONCLUSIONS This study emphasizes the importance of ABC proteins and their relation to the resistance mechanism in hospital environments and they may be an important target for the development of compounds able to unsettle drug extrusion.

doi: 10.1590/0074-02760170484
+ Corresponding author: This e-mail address is being protected from spambots. You need JavaScript enabled to view it.
Received 7 November 2017
Accepted 22 December 2017

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