非遗传性异质结是否促进遗传性耐药的发展？
Does Non-Genetic Heterogeneity Facilitate the Development of Genetic Drug Resistance?
摘要：
非遗传形式的抗微生物药物耐药性可能是由细胞间的变异性引起的，这种变异性不是遗传物质编码的。最近的研究数据也表明，非遗传机制可以促进遗传耐药性的发展。在这篇透视文章中，我们推测非遗传和遗传机制之间的相互作用如何影响药物治疗期间的微生物适应和进化。我们认为，细胞异质性所产生的基因表达的波动，表观遗传修饰，以及遗传变化有助于在不同的时间尺度的耐药性，这些机制之间的相互作用可能会影响病原体耐药性的演化动力学。因此，更好地了解耐药性的非遗传机制以及它们如何与遗传机制相互作用，将提高我们对抗抗生素耐药性的能力。
英文摘要：
Non-genetic forms of antimicrobial drug resistance can result from cell-to-cell variability that is not encoded in the genetic material. Data from recent studies also suggest that non-genetic mechanisms can facilitate the development of genetic drug resistance. In this Perspective article, we speculate on how the interplay between non-genetic and genetic mechanisms may affect microbial adaptation and evolution during drug treatment. We argue that cellular heterogeneity arising from fluctuations in gene expression, epigenetic modifications, as well as genetic changes contributes to drug resistance at different timescales, and that the interplay between these mechanisms may influence the evolutionary dynamics of pathogen resistance. Accordingly, developing a better understanding of non-genetic mechanisms in drug resistance and how they interact with genetic mechanisms will enhance our ability to combat antimicrobial resistance.
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