While the action of many antimicrobial drugs is well understood at the molecular level, a systems-level physiological response to antibiotics remains largely unexplored. This work considers fluctuation dynamics of both the chromosome and cytosol in Escherichia coli, and their response to sublethal treatments of a clinically important antibiotic, rifampicin. We precisely quantify the changes in dynamics of chromosomal loci and cytosolic aggregates (a rheovirus nonstructural protein known as μNS-GFP), measuring short time-scale displacements across several hours of drug exposure. To achieve this we develop an empirical method correcting for photo-bleaching and loci size effects. This procedure allows us to characterize the dynamic response to rifampicin in different growth conditions, including a customised microfluidic device. We find that sub-lethal doses of rifampicin cause a small but consistent increase in motility of both the chromosomal loci and cytosolic aggregates. Chromosomal and cytosolic responses are consistent with each other and between different growth conditions.

Both genome and cytosol dynamics change in E. coli challenged with sublethal rifampicin / M. Wlodarski, B. Raciti, J. Kotar, M. Cosentino Lagomarsino, M. Gillian, P. Cicuta. - In: PHYSICAL BIOLOGY. - ISSN 1478-3967. - 14:1(2017 Feb 16), pp. 015005.1-015005.10.

Both genome and cytosol dynamics change in E. coli challenged with sublethal rifampicin

M. Cosentino Lagomarsino;
2017-02-16

Abstract

While the action of many antimicrobial drugs is well understood at the molecular level, a systems-level physiological response to antibiotics remains largely unexplored. This work considers fluctuation dynamics of both the chromosome and cytosol in Escherichia coli, and their response to sublethal treatments of a clinically important antibiotic, rifampicin. We precisely quantify the changes in dynamics of chromosomal loci and cytosolic aggregates (a rheovirus nonstructural protein known as μNS-GFP), measuring short time-scale displacements across several hours of drug exposure. To achieve this we develop an empirical method correcting for photo-bleaching and loci size effects. This procedure allows us to characterize the dynamic response to rifampicin in different growth conditions, including a customised microfluidic device. We find that sub-lethal doses of rifampicin cause a small but consistent increase in motility of both the chromosomal loci and cytosolic aggregates. Chromosomal and cytosolic responses are consistent with each other and between different growth conditions.
Anti-Bacterial Agents, pharmacology; Chromosomes, Bacterial, drug effects, genetics; Escherichia coli, cytology, drug effects, genetics; Escherichia coli Infections, drug therapy, microbiology; Genome, Bacterial, drug effects; Humans; Rifampin, pharmacology
Settore FIS/02 - Fisica Teorica, Modelli e Metodi Matematici
Settore FIS/03 - Fisica della Materia
Settore BIO/11 - Biologia Molecolare
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/608078
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