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Article: Genotypic, phenotypic and proteomic characterization of Candida glabrata during sequential fluconazole exposure

TitleGenotypic, phenotypic and proteomic characterization of Candida glabrata during sequential fluconazole exposure
Authors
KeywordsCandida
Fluconazole resistance
Hemolysin
Metallothionein
Virulence
Issue Date2011
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=2041-1618&site=1
Citation
Journal of Investigative and Clinical Dentistry, 2011, v. 2 n. 2, p. 117-127 How to Cite?
AbstractAbstract Aim: Candida glabrata is a major pathogen in humans known to be intrinsically resistant to fluconazole. However, genotypic, phenotypic, and proteomic changes associated with reduced susceptibility to fluconazole are not properly understood. The aim of this study was to observe specific phenotypic, chromosomal, and proteomic alterations in a Candida glabrata strain sequentially exposed to fluconazole. Methods: Candida glabrata was exposed to increased concentrations of fluconazole in RPMI for 55 days. Phenotypic changes were evaluated using standard assays. Molecular/proteomic changes in C. glabrata were analyzed by contour-clamped homogeneous electric field electrophoresis, reverse transcription–polymerase chain reaction, and mass spectrometry. Results: Candida glabrata demonstrated increased fluconazole resistance (>256 μg/mL), with extensive cross-resistance to ketoconazole (0.38–3.0 μg), itraconazole (8 to >32 μg), and voriconazole (0.125–1.5 μg). Morphologically dissimilar colonies on RPMI/fluconazole agar demonstrated variable chromosomal profiles compared with the control isolate. Stable chromosomal changes were associated with a significantly higher (P < 0.05) mRNA level of the hemolysin gene compared with the control. Phenotypic switching on CuSO4 agar was associated with variable metallothionein mRNA transcription levels. The proteome analysis of a fluconazole-resistant offshoot demonstrated a total of 98 protein spots, 25 showing a twofold upregulation. Conclusion:  Fluconazole exposure initiates the chance evolution of a new colonizing population with specific virulence traits.
Persistent Identifierhttp://hdl.handle.net/10722/134342
ISSN
2015 SCImago Journal Rankings: 0.268

 

DC FieldValueLanguage
dc.contributor.authorSamaranayake, YHen_US
dc.contributor.authorCheung, BPKen_US
dc.contributor.authorYau, JYYen_US
dc.contributor.authorYeung, KWen_US
dc.contributor.authorSamaranayake, LPen_US
dc.date.accessioned2011-06-17T09:18:05Z-
dc.date.available2011-06-17T09:18:05Z-
dc.date.issued2011en_US
dc.identifier.citationJournal of Investigative and Clinical Dentistry, 2011, v. 2 n. 2, p. 117-127en_US
dc.identifier.issn2041-1618-
dc.identifier.urihttp://hdl.handle.net/10722/134342-
dc.description.abstractAbstract Aim: Candida glabrata is a major pathogen in humans known to be intrinsically resistant to fluconazole. However, genotypic, phenotypic, and proteomic changes associated with reduced susceptibility to fluconazole are not properly understood. The aim of this study was to observe specific phenotypic, chromosomal, and proteomic alterations in a Candida glabrata strain sequentially exposed to fluconazole. Methods: Candida glabrata was exposed to increased concentrations of fluconazole in RPMI for 55 days. Phenotypic changes were evaluated using standard assays. Molecular/proteomic changes in C. glabrata were analyzed by contour-clamped homogeneous electric field electrophoresis, reverse transcription–polymerase chain reaction, and mass spectrometry. Results: Candida glabrata demonstrated increased fluconazole resistance (>256 μg/mL), with extensive cross-resistance to ketoconazole (0.38–3.0 μg), itraconazole (8 to >32 μg), and voriconazole (0.125–1.5 μg). Morphologically dissimilar colonies on RPMI/fluconazole agar demonstrated variable chromosomal profiles compared with the control isolate. Stable chromosomal changes were associated with a significantly higher (P < 0.05) mRNA level of the hemolysin gene compared with the control. Phenotypic switching on CuSO4 agar was associated with variable metallothionein mRNA transcription levels. The proteome analysis of a fluconazole-resistant offshoot demonstrated a total of 98 protein spots, 25 showing a twofold upregulation. Conclusion:  Fluconazole exposure initiates the chance evolution of a new colonizing population with specific virulence traits.-
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=2041-1618&site=1-
dc.relation.ispartofJournal of Investigative and Clinical Dentistryen_US
dc.rightsThe definitive version is available at www3.interscience.wiley.com-
dc.subjectCandida-
dc.subjectFluconazole resistance-
dc.subjectHemolysin-
dc.subjectMetallothionein-
dc.subjectVirulence-
dc.titleGenotypic, phenotypic and proteomic characterization of Candida glabrata during sequential fluconazole exposureen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=2041-1618&volume=2&issue=2&spage=117&epage=127&date=2011&atitle=Genotypic,+phenotypic+and+proteomic+characterization+of+Candida+glabrata+during+sequential+fluconazole+exposure-
dc.identifier.emailSamaranayake, YH: hema@hkucc.hku.hken_US
dc.identifier.emailCheung, BPK: bpkcheun@hkucc.hku.hken_US
dc.identifier.emailYau, JYY: yaujyy@hkucc.hku.hken_US
dc.identifier.emailYeung, KW: skwyeung@hku.hken_US
dc.identifier.emailSamaranayake, LP: lakshman@hku.hken_US
dc.identifier.doi10.1111/j.2041-1626.2011.00044.x-
dc.identifier.hkuros185730en_US
dc.identifier.volume2en_US
dc.identifier.issue2-
dc.identifier.spage117en_US
dc.identifier.epage127en_US

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