Contributions of intra- and extracellular antibiotic degradation to collective β-lactam survival
6 affiliations
- 1Department of Medical Biochemistry and Microbiology, Uppsala University
- 2Institute for Biological Physics, Department of Physics, University of Cologne
- 3Institut für Theoretische Physik II - Soft Matter, Department of Physics, Heinrich-Heine-Universität
- 4Institute of Ecology and Evolution, Department of Biology, University of Bern
- 5Swiss Institute of Bioinformatics
- 6Laboratory of Genetics, Department of Plant Sciences, Wageningen University & Research
Abstract
Collective antibiotic resistance occurs when populations of bacteria survive antibiotic treatments that are lethal to individual bacteria, which affects the efficacy of drug therapies. An important mechanism of collective resistance against widely used β -lactams is the production of drug-degrading β -lactamases. Here, we integrate experiments with mathematical modeling to understand the collective survival of Escherichia coli challenged with cefotaxime. At near-lethal cefotaxime concentrations, we observe complex dynamics, involving initial biomass growth due to filamentation, followed by death, and subsequently growth recovery. We show that production of AmpC, a chromosomal β -lactamase, is responsible for cefotaxime degradation, allowing the resumption of cell division in surviving filaments. The detoxification of the environment proceeds through CTX hydrolysis by AmpC in the periplasm of intact cells, as well as extracellularly after cell lysis. Our model predicts the recovery time from molecular parameters, and quantifies the relative roles of periplasmic and extracellular degradation for two strains of E. coli that differ in the degree of privatization of AmpC hydrolysis. Our findings suggest that β -lactam survival of bacterial infections depends on a combination of intra- and extracellular β -lactamase activity, which will likely vary among isolates.
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BibTeX
@article{gross2026contributions,
title = {{Contributions of intra- and extracellular antibiotic degradation to collective β-lactam survival}},
author = {Rotem Gross and Muhittin Mungan and Suman G. Das and Melih Yüksel and Berenike Maier and Tobias Bollenbach and J. Arjan G. M. de Visser and Joachim Krug},
journal = {Proceedings of the National Academy of Sciences},
year = {2026},
month = jul,
doi = {10.1073/pnas.2526410123},
url = {https://doi.org/10.1073/pnas.2526410123},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Contributions of intra- and extracellular antibiotic degradation to collective β-lactam survival
AU - Rotem Gross
AU - Muhittin Mungan
AU - Suman G. Das
AU - Melih Yüksel
AU - Berenike Maier
AU - Tobias Bollenbach
AU - J. Arjan G. M. de Visser
AU - Joachim Krug
PY - 2026
DA - 2026/07/15
JO - Proceedings of the National Academy of Sciences
DO - 10.1073/pnas.2526410123
UR - https://doi.org/10.1073/pnas.2526410123
AB - Collective antibiotic resistance occurs when populations of bacteria survive antibiotic treatments that are lethal to individual bacteria, which affects the efficacy of drug therapies. An important mechanism of collective resistance against widely used β -lactams is the production of drug-degrading β -lactamases. Here, we integrate experiments with mathematical modeling to understand the collective survival of Escherichia coli challenged with cefotaxime. At near-lethal cefotaxime concentrations, we observe complex dynamics, involving initial biomass growth due to filamentation, followed by death, and subsequently growth recovery. We show that production of AmpC, a chromosomal β -lactamase, is responsible for cefotaxime degradation, allowing the resumption of cell division in surviving filaments. The detoxification of the environment proceeds through CTX hydrolysis by AmpC in the periplasm of intact cells, as well as extracellularly after cell lysis. Our model predicts the recovery time from molecular parameters, and quantifies the relative roles of periplasmic and extracellular degradation for two strains of E. coli that differ in the degree of privatization of AmpC hydrolysis. Our findings suggest that β -lactam survival of bacterial infections depends on a combination of intra- and extracellular β -lactamase activity, which will likely vary among isolates.
SN - 0027-8424
SN - 1091-6490
ER -