A Clinical Isolate of Candida albicans with Mutations in ERG11 (Encoding Sterol 14α-Demethylase) and ERG5 (Encoding C22 Desaturase) Is Cross Resistant to Azoles and Amphotericin B

被引：119

作者：

Martel, Claire M. ^{[1
,2
]}

Parker, Josie E. ^{[1
,2
]}

Bader, Oliver ^{[3
,4
]}

Weig, Michael ^{[3
,4
]}

Gross, Uwe ^{[3
,4
]}

Warrilow, Andrew G. S. ^{[1
,2
]}

Kelly, Diane E. ^{[1
,2
]}

Kelly, Steven L. ^{[1
,2
]}

机构：

[1] Swansea Univ, Inst Life Sci, Swansea SA2 8PP, W Glam, Wales

[2] Swansea Univ, Sch Med, Swansea SA2 8PP, W Glam, Wales

[3] Univ Med Ctr Gottingen, Inst Med Microbiol, Gottingen, Germany

[4] German Natl Reference Ctr System Mycoses, Gottingen, Germany

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2010年 / 54卷 / 09期

关键词：

AMINO-ACID SUBSTITUTION; ANTIFUNGAL AGENTS; FLUCONAZOLE RESISTANCE; AIDS PATIENTS; LANOSTEROL; 14-ALPHA-DEMETHYLASE; REDUCED AFFINITY; IN-VIVO; MECHANISMS; STRAINS; DEMETHYLASE;

D O I：

10.1128/AAC.00303-10

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

A clinical isolate of Candida albicans was identified as an erg5 (encoding sterol C22 desaturase) mutant in which ergosterol was not detectable and ergosta 5,7-dienol comprised >80% of the total sterol fraction. The mutant isolate (CA108) was resistant to fluconazole, voriconazole, itraconazole, ketoconazole, and clotrimazole (MIC values, 64, 8, 2, 1, and 2 mu g ml(-1), respectively); azole resistance could not be fully explained by the activity of multidrug resistance pumps. When susceptibility tests were performed in the presence of a multidrug efflux inhibitor (tacrolimus; FK506), CA108 remained resistant to azole concentrations higher than suggested clinical breakpoints for C. albicans (efflux-inhibited MIC values, 16 and 4 mu g ml(-1) for fluconazole and voriconazole, respectively). Gene sequencing revealed that CA108 was an erg11 erg5 double mutant harboring a single amino acid substitution (A114S) in sterol 14 alpha-demethylase (Erg11p) and sequence repetition (10 duplicated amino acids), which nullified C22 desaturase (Erg5p) function. Owing to a lack of ergosterol, CA108 was also resistant to amphotericin B (MIC, 2 mu g ml(-1)). This constitutes the first report of a C. albicans erg5 mutant isolated from the clinic.

引用

页码：3578 / 3583

页数：6