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Antibiotic perseverance increases the risk of resistance development
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.ORCID-id: 0000-0001-8457-7699
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.ORCID-id: 0000-0001-7355-9751
Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi.ORCID-id: 0000-0001-5522-1810
2023 (engelsk)Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 120, nr 2, artikkel-id e2216216120Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Proceedings of the National Academy of Sciences (PNAS), 2023. Vol. 120, nr 2, artikkel-id e2216216120
Emneord [en]
cellular heterogeneity, mutation frequency, single-cell microscopy, rifampicin, antibiotic resistance evolution
HSV kategori
Forskningsprogram
Biologi med inriktning mot mikrobiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-497793DOI: 10.1073/pnas.2216216120ISI: 000969771500002PubMedID: 36595701OAI: oai:DiVA.org:uu-497793DiVA, id: diva2:1741173
Forskningsfinansiär
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)Tilgjengelig fra: 2023-03-03 Laget: 2023-03-03 Sist oppdatert: 2025-02-20bibliografisk kontrollert

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