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棘白菌素类耐药的代价:FKS1 热点突变对白色念珠菌适应性和毒力的影响。

Resistance to echinocandins comes at a cost: the impact of FKS1 hotspot mutations on Candida albicans fitness and virulence.

机构信息

Infectious Diseases Unit, Tel Aviv Medical Center and Sackler School of Medicine, Tel Aviv, Israel.

出版信息

Virulence. 2012 Jan-Feb;3(1):95-7. doi: 10.4161/viru.3.1.18886. Epub 2012 Jan 1.

Abstract

The emergence of Candida strains carrying FKS1 hotspot mutations associated with resistance to echinocandins is cause for concern. However, to assess the potential of such strains to spread within the community and cause lethal infection, the impact of FKS1 mutations on Candida fitness must be determined. We present evidence that C. albicans fks1 mutations carry significant fitness and virulence costs, which are associated with the production of a thickened, chitin-rich cell wall, impaired filamentation and induction of a dampened inflammatory response. If these phenotypic changes remain stable, they can serve as a basis for rational design of strategies to control the spread of echinocandin resistance.

摘要

携带与棘白菌素类药物耐药相关的 FKS1 热点突变的念珠菌菌株的出现令人担忧。然而,要评估此类菌株在社区内传播并导致致命感染的潜力,就必须确定 FKS1 突变对念珠菌适应性的影响。我们提供的证据表明,白念珠菌 fks1 突变具有显著的适应性和毒力代价,这与细胞壁增厚、几丁质含量增加、菌丝形成受损以及炎症反应减弱有关。如果这些表型变化保持稳定,它们可以为合理设计控制棘白菌素类药物耐药传播的策略提供依据。

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