臨床検査64巻7号

2020年07月発行

今月の特集2 薬剤耐性カンジダを考える

カンジダに対する抗真菌薬の作用機序と耐性機構

著者： 名木稔¹

所属機関： ¹国立感染症研究所真菌部

ページ範囲：P.786 - P.790

Point

●主要な抗真菌薬の標的分子は細胞膜と細胞壁の成分およびその生合成経路にある．

●主なアゾール耐性機構は，薬剤排出ポンプの高発現，標的をコードするERG11の変異・過剰発現などである．

●キャンディン耐性は，標的をコードするFKS遺伝子に変異が生じることで発生する．

参考文献

1）Arendrup MC, Patterson TF：Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment. J Infect Dis　216(suppl3)：S445-S451，2017

2）Sanglard D, Ischer F, Calabrese D, et al：The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrob Agents Chemother　43：2753-2765，1999

3）Moran GP, Sanglard D, Donnelly SM, et al：Identification and expression of multidrug transporters responsible for fluconazole resistance in Candida dubliniensis. Antimicrob Agents Chemother　42：1819-1830，1998

4）Rybak JM, Doorley LA, Nishimoto AT, et al：Abrogation of Triazole Resistance upon Deletion of CDR1 in a Clinical Isolate of Candida auris. Antimicrob Agents Chemother　63.pii：e00057-19，2019

5）Marichal P, Koymans L, Willemsens S, et al：Contribution of mutations in the cytochrome P450 14alpha-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans. Microbiology　145：2701-2713，1999

6）Xiang MJ, Liu JY, Ni PH, et al：Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans. FEMS Yeast Res　13：386-393，2013

7）MacPherson S, Akache B, Weber S, et al：Candida albicans zinc cluster protein Upc2p confers resistance to antifungal drugs and is an activator of ergosterol biosynthetic genes. Antimicrob Agents Chemother　49：1745-1752，2005

8）Choi MJ, Won EJ, Shin JH, et al：Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates. Antimicrob Agents Chemother　60：3653-3661，2016

9）Miyazaki T, Miyazaki Y, Izumikawa K, et al：Fluconazole treatment is effective against a Candida albicans erg3/erg3 mutant in vivo despite in vitro resistance. Antimicrob Agents Chemother　50：580-586，2006

10）Nakayama H, Tanabe K, Bard M, et al：The Candida glabrata putative sterol transporter gene CgAUS1 protects cells against azoles in the presence of serum. J Antimicrob Chemother　60：1264-1272，2007

11）Garcia-Effron G, Park S, Perlin DS：Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints. Antimicrob Agents Chemother　53：112-122，2009

12）Garcia-Effron G, Lee S, Park S, et al：Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-beta-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother　53：3690-3699，2009

13）Niimi K, Maki K, Ikeda F, et al：Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility. Antimicrob Agents Chemother　50：1148-1155，2006

14）Nolte FS, Parkinson T, Falconer DJ, et al：Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia. Antimicrob Agents Chemother　41：196-199，1997

15）Hope WW, Tabernero L, Denning DW, et al：Molecular mechanisms of primary resistance to flucytosine in Candida albicans. Antimicrob Agents Chemother　48：4377-4386，2004

16）Dodgson AR, Dodgson KJ, Pujol C, et al：Clade-specific flucytosine resistance is due to a single nucleotide change in the FUR1 gene of Candida albicans. Antimicrob Agents Chemother　48：2223-2227，2004