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.OBJECTIVEThe aim of this study was to characterise the azole resistance mechanism presented by a C. glabrata clinical isolate from a Brazilian university hospital.METHODSAzole susceptibility assays, chemosensitisation, flow cytometry and mass spectrometry were performed.FINDINGSOur 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 CONCLUSIONSThis 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.
Highlights
Candida glabrata ranks second in epidemiological surveillance studies, and is considered one of the main human yeast pathogens
C. glabrata is the second most common cause of mucosal and blood-stream candidiasis, it ranks in epidemiological surveillance studies after C. albicans and it is considered as one of the main human yeast pathogens (Pfaller & Diekema 2007, Muadcheingka & Tantivitayakul 2015)
Fig. 3: identification of the ABC transporter peptides from Candida glabrata (R) clinical isolate by electrospray ionisation (ESI)-MS/MS. (A) Plasma membrane preparations of control Saccharomyces cerevisiae mutant strains and clinical isolates separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as follows: 1- null mutant; 2- AD/124567 (Pdr5p ABC transporter of S. cerevisiae) (+); 3- AD/CgCDR1 (CgCdr1p of C. glabrata); 4- AD/CgCDR2 (CgCdr2p of C. glabrata); 5- C. glabrata (R); 6- C. glabrata (S) and 7- C. glabrata ATCC2001
Summary
Chemosensitisation, flow cytometry and mass spectrometry were performed. Clinical isolates and control strains - Three resistant and one susceptible C. glabrata clinical isolate were selected from ninety-three Candida strains due to their high/low fluconazole (FCZ) resistance (Neves-Junior et al 2015). These clinical isolates were obtained from patients attended at the University Hospital of the Federal University of Juiz de Fora, MG, Brazil, between 2012 and 2014. The Candida isolates were isolated from clinical materials obtained from ambulatory patients or from online | memorias.ioc.fiocruz.br. These clinical materials were mainly urine, feces, catheter, blood and other secretions. ATCC 2001 C. glabrata was used as control for tests using Candida strains
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
