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Antibiotic perseverance increases the risk of resistance development
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0001-8457-7699
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0001-7355-9751
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.ORCID iD: 0000-0001-5522-1810
2023 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 120, no 2, article id e2216216120Article in journal (Refereed) Published
Abstract [en]

The rise of antibiotic-resistant bacterial infections poses a global threat. Antibiotic resistance development is generally studied in batch cultures which conceals the heterogeneity in cellular responses. Using single-cell imaging, we studied the growth response of Escherichia coli to sub-inhibitory and inhibitory concentrations of nine antibiotics. We found that the heterogeneity in growth increases more than what is expected from growth rate reduction for three out of the nine antibiotics tested. For two antibiotics (rifampicin and nitrofurantoin), we found that sub-populations were able to maintain growth at lethal antibiotic concentrations for up to 10 generations. This perseverance of growth increased the population size and led to an up to 40-fold increase in the frequency of antibiotic resistance mutations in gram-negative and gram-positive species. We conclude that antibiotic perseverance is a common phenomenon that has the potential to impact antibiotic resistance development across pathogenic bacteria.

Place, publisher, year, edition, pages
Proceedings of the National Academy of Sciences (PNAS), 2023. Vol. 120, no 2, article id e2216216120
Keywords [en]
cellular heterogeneity, mutation frequency, single-cell microscopy, rifampicin, antibiotic resistance evolution
National Category
Microbiology Biophysics
Research subject
Biology with specialization in Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-497793DOI: 10.1073/pnas.2216216120ISI: 000969771500002PubMedID: 36595701OAI: oai:DiVA.org:uu-497793DiVA, id: diva2:1741173
Funder
EU, European Research Council, 885360Knut and Alice Wallenberg Foundation, 2016.0077Knut and Alice Wallenberg Foundation, 2017.0291Knut and Alice Wallenberg Foundation, 2019.0439Swedish Research Council, 2018-05973Swedish Foundation for Strategic Research, ARC19-0016eSSENCE - An eScience CollaborationSwedish National Infrastructure for Computing (SNIC)Available from: 2023-03-03 Created: 2023-03-03 Last updated: 2025-02-20Bibliographically approved

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Brandis, GerritLarsson, JimmyElf, Johan

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