Department of Infectious Diseases, Infection Control and Employee Health, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
J Infect Dis. 2011 Aug 15;204(4):626-35. doi: 10.1093/infdis/jir351.
The identification of FKS1 mutations in Candida albicans associated with echinocandin resistance has raised concerns over the spread of drug-resistant strains. We studied the impact of fks1 mutations on C. albicans virulence and fitness. Compared with wild-type strains for FKS1, echinocandin-resistant C. albicans strains with homozygous fks1 hot-spot mutations had reduced maximum catalytic capacity of their glucan synthase complexes and thicker cell walls attributable to increased cell wall chitin content. The fks1 mutants with the highest chitin contents had reduced growth rates and impaired filamentation capacities. Fks1 mutants were hypovirulent in fly and mouse models of candidiasis, and this phenotype correlated with the cell wall chitin content. In addition, we observed reduced fitness of echinocandin-resistant C. albicans in competitive mixed infection models. We conclude that fks1 mutations that confer echinocandin resistance come at fitness and virulence costs, which may limit their epidemiological and clinical impact.
氟康唑耐药相关白念珠菌 FKS1 基因突变的鉴定引起了人们对耐药菌株传播的关注。我们研究了 fks1 突变对白色念珠菌毒力和适应性的影响。与 FKS1 野生型菌株相比，具有 FKS1 热点突变纯合子的氟康唑耐药白念珠菌菌株的葡聚糖合酶复合物的最大催化能力降低，细胞壁变厚归因于细胞壁几丁质含量增加。几丁质含量最高的 fks1 突变体的生长速度降低，菌丝形成能力受损。Fks1 突变体在念珠菌病的蝇和鼠模型中表现出低毒力，这种表型与细胞壁几丁质含量相关。此外，我们在竞争性混合感染模型中观察到氟康唑耐药白念珠菌的适应性降低。我们的结论是，赋予氟康唑耐药性的 fks1 突变会带来适应性和毒力代价，这可能限制了它们的流行病学和临床影响。
