Does transcriptional heterogeneity facilitate the development of genetic drug resistance?

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. 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 contribute to drug resistance at different timescales, and that the interplay between these mechanisms enhance pathogen resistance. Accordingly, developing a better understanding of the role of non-genetic mechanisms in drug resistance and how they interact with genetic mechanisms will enhance our ability to combat antimicrobial resistance.

Automated summary

Non-genetic mechanisms can contribute to antimicrobial resistance and interact with genetic mechanisms to enhance pathogen resistance. Cellular heterogeneity and gene expression fluctuations play a role in drug resistance at different timescales.