Dresden 2017 – scientific programme

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BP: Fachverband Biologische Physik

BP 4: Systems Biology & Gene Expression and Signalling

BP 4.1: Invited Talk

Monday, March 20, 2017, 15:00–15:30, ZEU 250

Antibiotic-induced gene expression noise and cross-protection at the single-cell level — •Tobias Bollenbach — University of Cologne, Germany

Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain stress responses are known to ’cross-protect’ bacteria from other stressors, it is unclear if cellular responses to antibiotics can have a similar protective role. By measuring the dynamic genome-wide transcriptional response of Escherichia coli to four antibiotics, we found that trimethoprim induces a rapid and strong acid stress response pulse which protects bacteria from subsequent exposure to acid. We then combined microfluidics and time-lapse imaging to monitor survival and the dynamics of acid stress response induction in single cells. The fraction of surviving cells followed a simple exponential decay and thus appeared consistent with a memoryless Poisson process. Interestingly, however, the noisy expression of one of the major acid resistance genes explained the great spread in single-cell survival times. Simultaneous measurements of gene expression and pH using a ratiometric sensor revealed that cells with higher expression of acid resistance genes upon trimethoprim exposure maintain higher intracellular pH and survive the acid shock better. The seemingly stochastic single-cell survival times under acid stress therefore become predictable once their underlying molecular cause is identified. Overall, this work provides a roadmap for the systematic identification of molecular mechanisms behind single-cell cross-protection between antibiotics and other stressors.