Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance.
Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance.
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DOI：
10.1038/ncomms11128
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发表时间：
2016-03-29
影响因子：
16.6
通讯作者：
Perlin DS
中科院分区：
文献类型：
--
作者：
Healey KR;Zhao Y;Perez WB;Lockhart SR;Sobel JD;Farmakiotis D;Kontoyiannis DP;Sanglard D;Taj-Aldeen SJ;Alexander BD;Jimenez-Ortigosa C;Shor E;Perlin DS
真菌病原体光滑念珠菌已成为一个主要的健康威胁，因为它很容易获得耐药性的多种药物类别，包括三唑和/或棘白菌素。到目前为止，尚未在该生物体中描述促进对多种药物类别产生耐药性的细胞机制。在这里，我们证明了由错配修复缺陷引起的突变表型在C。光滑临床分离株。携带错配修复基因MSH 2改变的菌株在体外和小鼠定殖模型中表现出更高的突破性抗真菌治疗倾向，并且以高速率回收（所有C. glabrata恢复）。这种遗传机制促进了对多种抗真菌药物的耐药性的获得，至少部分解释了与C.光滑的我们预计，确定感染菌株中的MSH 2缺陷可能会影响抗真菌药物治疗患者的管理。 真菌病原体光滑念珠菌容易获得对多种类型的抗真菌药物的耐药性。在这里，Healey等人表明，C。glabrata临床分离株通常携带参与DNA错配修复的基因突变，这与抗真菌药物耐药性的增加有关。
The fungal pathogen Candida glabrata has emerged as a major health threat since it readily acquires resistance to multiple drug classes, including triazoles and/or echinocandins. Thus far, cellular mechanisms promoting the emergence of resistance to multiple drug classes have not been described in this organism. Here we demonstrate that a mutator phenotype caused by a mismatch repair defect is prevalent in C. glabrata clinical isolates. Strains carrying alterations in mismatch repair gene MSH2 exhibit a higher propensity to breakthrough antifungal treatment in vitro and in mouse models of colonization, and are recovered at a high rate (55% of all C. glabrata recovered) from patients. This genetic mechanism promotes the acquisition of resistance to multiple antifungals, at least partially explaining the elevated rates of triazole and multi-drug resistance associated with C. glabrata. We anticipate that identifying MSH2 defects in infecting strains may influence the management of patients on antifungal drug therapy. The fungal pathogen Candida glabrata readily acquires resistance to multiple types of antifungal drugs. Here, Healey et al. show that C. glabrata clinical isolates often carry mutations in a gene involved in DNA mismatch repair, and this is associated with increased propensity to develop antifungal resistance.
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影响因子：
2.8
作者：
Briones-Martin-del-Campo, Marcela;Orta-Zavalza, Emmanuel;De Las Penas, Alejandro
通讯作者：
De Las Penas, Alejandro
影响因子：
4.9
作者：
Pultz, NJ;Stiefel, U;Donskey, CJ
通讯作者：
Donskey, CJ
影响因子：
3.6
作者：
Healey KR;Katiyar SK;Raj S;Edlind TD
通讯作者：
Edlind TD
影响因子：
4.9
作者：
Bizerra, Fernando Cesar;Jimenez-Ortigosa, Cristina;Colombo, Arnaldo L.
通讯作者：
Colombo, Arnaldo L.
影响因子：
4.9
作者：
Arendrup, Maiken Cavling;Perlin, David S.;Hope, William
通讯作者：
Hope, William