title: Proteomic analysis reveals that Adh1p is involved in a synergistic fluconazole and tetrandrine mechanism against Candida albicans.
abstract: We previously showed that Adh1p participates in fluconazole (FLC) resistance in Candida albicans through a mechanism that may involve efflux pumps. We also found that the concomitant use of tetrandrine (TET) and FLC provided a synergistic action against C. albicans and that the mechanism of action could be related to inhibition of a drug efflux system. To determine whether Adh1p participates in the synergistic antifungal activity of TET against C. albicans, we performed a comparative proteomic study comparing cells treated with FLC and/or TET in FLC-sensitive CA-3 and untreated control cells. Proteins were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), and differentially expressed proteins were identified through matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF/TOF) mass spectrometry. The resulting data were searched against a C. albicans protein database. Our analyses identified six differentially expressed proteins; four (Eno1p, Adh1p, Slb1p, and Tdh1p) were down-regulated, and two (Xyl2p, and Cdc19p) were up-regulated. The Adh1p mRNA levels were consistent with the Adh1p protein levels in all of the groups. The results suggest that Adh1p participates in the synergistic antifungal activity of TET against C. albicans.
authors.affiliation: The First Affiliated Hospital and Institute of Mycology of Jinan University, Guangzhou, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Ge-Hua
authors.initials: GH
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital and Institute of Mycology of Jinan University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: The First Affiliated Hospital and Institute of Mycology of Jinan University, Guangzhou, China.
authors.forename: Lai-Qiang
authors.initials: LQ
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Si
authors.initials: S
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital and Institute of Mycology of Jinan University, Guangzhou, China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Song
authors.affiliation: The First Affiliated Hospital and Institute of Mycology of Jinan University, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000935:Antifungal Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D025141:Drug Resistance, Fungal; D015180:Electrophoresis, Gel, Two-Dimensional; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D013058:Mass Spectrometry; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic; D014357:Trypsin / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D044182:Benzylisoquinolines; D005656:Fungal Proteins; C009438:tetrandrine; D015725:Fluconazole; D000426:Alcohol Dehydrogenase; D014357:Trypsin