Escherichia coli survival in response to ciprofloxacin antibiotic stress correlates with increased nucleoid length and effective misfolded protein management

Author:

Butler George1ORCID,Bos Julia23,Austin Robert H.3,Amend Sarah R.1,Pienta Kenneth J.1

Affiliation:

1. Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA

2. Institut Pasteur, Université de Paris Cité, CNRS UMR 3525, Unité Plasticité du Génome Bactérien, Paris, France

3. Department of Physics, Princeton University, Princeton, NJ, USA

Abstract

The evolution of antibiotic resistance is a fundamental problem in disease management but is rarely quantified on a single-cell level owing to challenges associated with capturing the spatial and temporal variation across a population. To evaluate cell biological phenotypic responses, we tracked the single-cell dynamics of filamentous bacteria through time in response to ciprofloxacin antibiotic stress. We measured the degree of phenotypic variation in nucleoid length and the accumulation of protein damage under ciprofloxacin antibiotic and quantified the impact on bacterial survival. Increased survival was correlated with increased nucleoid length and the variation in this response was inversely correlated with antibiotic concentration. Survival time was also increased through clearance of misfolded proteins, an unexpected mechanism of stress relief deployed by the filamentous bacteria. Our results reveal a diverse range of survival tactics employed by bacteria in response to ciprofloxacin and suggest potential evolutionary routes to resistance.

Funder

Patrick C. Walsh Prostate Cancer Research Fund

NSF Center for the Physics of Biological Function

National Cancer Institute

U.S. Department of Defense

Prostate Cancer Foundation

Publisher

The Royal Society

Subject

Multidisciplinary

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