Forecasting cell fate during antibiotic exposure using stochastic gene expression

Nicholas A. Rossi,I. El Meouche,M. Dunlop

Published 2019 in Communications Biology

ABSTRACT

Antibiotic killing does not occur at a single, precise time for all cells within a population. Variability in time to death can be caused by stochastic expression of genes, resulting in differences in endogenous stress-resistance levels between individual cells in a population. Here we investigate whether single-cell differences in gene expression prior to antibiotic exposure are related to cell survival times after antibiotic exposure for a range of genes of diverse function. We quantified the time to death of single cells under antibiotic exposure in combination with expression of reporters. For some reporters, including genes involved in stress response and cellular processes like metabolism, the time to cell death had a strong relationship with the initial expression level of the genes. Our results highlight the single-cell level non-uniformity of antibiotic killing and also provide examples of key genes where cell-to-cell variation in expression is strongly linked to extended durations of antibiotic survival. Nicholas Rossi et al. find that bacterial cell survival following antibiotic exposure can be predicted by the expression levels of specific genes prior to antibiotic treatment. They test 15 genes using a reporter system and find that single-cell gene expression predicts survival time in an antibiotic-specific manner.

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