  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.
