title: The putative ABC transporter encoded by the orf19.4531 plays a role in the sensitivity of Candida albicans cells to azole antifungal drugs.
abstract: ATP-binding cassette (ABC) transporters constitute a large superfamily of integral membrane proteins in prokaryotic and eukaryotic cells. In the human fungal pathogen Candida albicans, there are 28 genes encoding ABC transporters and many of them have not been characterized so far. The orf19.4531 (also known as IPF7530) encodes a putative ABC transporter. In this study, we have demonstrated that disruption of orf19.4531 causes C. albicans cells to become tolerant to azoles, but not to polyene antifungals and terbinafine. Therefore, the protein encoded by orf19.4531 is involved in azole sensitivity and we name it as ROA1, the regulator of azole sensitivity 1 gene. Consistently, we show that the expression of ROA1 is responsive to treatment of either fluconazole or ketoconazole inC. albicans In addition, through a GFP tagging approach, Roa1 is localized in a small punctuate compartment adjacent to the vacuolar membrane. However, ROA1 is not essential for the in vitro filamentation of C. albicans cells.
authors.affiliation: The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China linghuojiang@hotmail.com.
authors.forename: Linghuo
authors.initials: L
authors.lastname: Jiang
authors.affiliation: The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Xu
authors.affiliation: The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Cao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Pinghui
authors.initials: P
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000935:Antifungal Agents / Q000378:metabolism* / Q000494:pharmacology; D001393:Azoles / Q000378:metabolism* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D055786:Gene Knockout Techniques; D007425:Intracellular Membranes / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009281:Naphthalenes / Q000378:metabolism / Q000494:pharmacology; D011090:Polyenes / Q000378:metabolism / Q000494:pharmacology; D000077291:Terbinafine
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D001393:Azoles; D009281:Naphthalenes; D011090:Polyenes; D000077291:Terbinafine
keywords: ABC transporter; Candida albicans; ROA1; antifungals; azole