Anderson James B
Department of Botany, 3359 Mississauga Road North, University of Toronto, Mississauga, Ontario, Canada L5L 1C6.
Nat Rev Microbiol. 2005 Jul;3(7):547-56. doi: 10.1038/nrmicro1179.
Like other microorganisms, fungi exist in populations that are adaptable. Under the selection imposed by antifungal drugs, drug-sensitive fungal pathogens frequently evolve resistance. Although the molecular mechanisms of resistance are well-characterized, there are few measurements of the impact of these mechanisms on pathogen fitness in different environments. To predict resistance before a new drug is prescribed in the clinic, the full spectrum of potential resistance mutations and the interactions among combinations of divergent mechanisms can be determined in evolution experiments. In the search for new strategies to manage drug resistance, measuring the limits of adaptation might reveal methods for trapping fungal pathogens in evolutionary dead ends.
与其他微生物一样,真菌以具有适应性的群体形式存在。在抗真菌药物施加的选择压力下,对药物敏感的真菌病原体经常会产生耐药性。尽管耐药性的分子机制已得到充分表征,但对于这些机制在不同环境中对病原体适应性的影响,却鲜有衡量。为了在临床开具新药之前预测耐药性,可以在进化实验中确定潜在耐药性突变的全谱以及不同机制组合之间的相互作用。在寻找应对耐药性的新策略时,测量适应性的极限可能会揭示将真菌病原体困在进化死胡同的方法。