KODO NaohikoDepartment of Medicine Research associate | |||
Last Updated :2024/04/25
Researcher Information
J-Global ID
Research Interests
- 薬剤排出ポンプ トランスポーター 殺菌剤 病原性真菌 薬剤耐性 多剤耐性 抗真菌剤 出芽酵母 遺伝学 分子生物学
Research Areas
Association Memberships
Published Papers
- Naohiko Kodo; Shoei Sakata; Toshiro MatsudaNucleus (India) Springer India 58 (3) 231 - 234 0976-7975 2015/12 [Refereed]
Gain-of-function mutations of Saccharomyces cerevisiae pleiotropic drug resistance (PDR) genes PDR1, PDR3, and YRR1 cause constitutive high expression of membrane-associated drug efflux pumps, resulting in the excretion of antifungal drugs. We previously identified a novel mutation of YRR1 that conferred salicylic acid (SA) resistance to S. cerevisiae BY4741 cells randomly mutagenized with ethyl methane sulfonate. Yeast cells carrying the yrr1–52 allele activated several drug efflux pumps and exhibited resistance to 4-nitroquinoline-N-oxide and cycloheximide. However, the activated genes and other factors that are directly involved in SA resistance remain unclear. Therefore, microarray analyses of total RNA extracted from yrr1–52 and wild-type cells during the logarithmic phase were performed. Twenty genes demonstrating > 2-fold higher expression than the wild-type were selected. Among the upregulated genes, YOR1, SNQ2, AZR1, and FLR1 encode transport proteins previously associated with drug efflux pumps. YOR1 and SNQ2, which encode an ATP-binding cassette (ABC) transporter, were investigated as candidate genes involved in SA resistance. Spot assay results showed no changes in SA susceptibility after disruption of YOR1 or SNQ2 on a background of YRR1 and yrr1–52, indicating that Yor1p and Snq2p are not involved in SA resistance. - Naohiko Kodo; Toshiro Matsuda; Syuichi Doi; Hiroshi MunakataBiochemical and Biophysical Research Communications 434 (1) 42 - 47 0006-291X 2013/04Yeast cells can extrude intracellular drugs through membrane-associated efflux pumps, such as ATP-binding cassette (ABC) transporters and members of the major facilitator superfamily. Gene expression of drug efflux pumps is regulated by several transcription factors involved in pleiotropic drug resistance (PDR). Salicylic acid (SA) possesses weak antifungal activity. Although the excretion mechanisms of some antifungal drugs have been revealed, the mechanism of SA extrusion remains unclear. To elucidate the mechanism of SA excretion, we screened SA-resistant mutants from random mutagenized Saccharomyces cerevisiae BY4741 cells. We successfully isolated 60 SA-resistant clones (KinSal001-060). KinSal052, one of the strongest SA-resistant clones, also exhibited resistance to 4-nitroquinoline-1-oxide and cycloheximide, indicating that it acquired the PDR phenotype. We identified a novel mutation in YRR1 conferring SA resistance to KinSal052. YRR1 encodes a Zn(II)2Cys6-type zinc-finger transcription factor that reportedly activates gene expression involved in PDR. Yeast cells carrying the yrr1 allele (yrr1-52) activated expression of several efflux pump-encoding genes, including YOR1, SNQ2, AZR1, and FLR1. These results suggested that SA resistance in KinSal052 is conferred by the overexpression of efflux pumps constitutively activated by the mutant form of Yrr1p. © 2013 Elsevier Inc.
Conference Activities & Talks
- 出芽酵母の多剤耐性研究より示唆されたヒト病原性真菌多剤耐性の問題点について [Not invited]小堂直彦第一回日本医真菌学会関西支部「深在性真菌症研究会」 2015/10
- 真菌の多剤耐性形質の分子機序の解明〜それから派生した応用研究〜 [Invited]小堂直彦遺伝学からの潮流—躍動の生命科学と教育— 2015/03
- 転写因子の突然変異によりもたらされる出芽酵母の多剤耐性形質の特徴 [Not invited]小堂 直彦; 松田 外志朗第58回日本医真菌学会総会・学術集会 2014/11
- Salicylic acid resistance is conferred by the overexpression of SNG1 in Saccharomyces cerevisiae [Not invited]小堂 直彦; 松田 外志朗; 土井 修市; 宗像 浩第36回日本分子生物学会年会 2013/12
- サリチル酸抵抗性を示す出芽酵母YRR1遺伝子上の突然変異の取得と解析 [Not invited]小堂 直彦; 土井 修市第33回日本分子生物学会年会 2010/12