Universität zu Köln

Saebelfeld, Manja, Das, Suman G., Hagenbeek, Arno, Krug, Joachim and de Visser, J. Arjan G. M. (2022). Stochastic establishment of beta-lactam-resistant Escherichia coli mutants reveals conditions for collective resistance. Proc. R. Soc. B-Biol. Sci., 289 (1974). LONDON: ROYAL SOC. ISSN 1471-2954

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Abstract

For antibiotic resistance to arise, new resistant mutants must establish in a bacterial population before they can spread via natural selection. Comprehending the stochastic factors that influence mutant establishment is crucial for a quantitative understanding of antibiotic resistance emergence. Here, we quantify the single-cell establishment probability of four Escherichia coli strains expressing beta-lactamase alleles with different activity against the antibiotic cefotaxime, as a function of antibiotic concentration in both unstructured (liquid) and structured (agar) environments. We show that concentrations well below the minimum inhibitory concentration (MIC) can substantially hamper establishment, particularly for highly resistant mutants. While the pattern of establishment suppression is comparable in both tested environments, we find greater variability in establishment probability on agar. Using a simple branching model, we investigate possible sources of this stochasticity, including environment-dependent lineage variability, but cannot reject other possible causes. Lastly, we use the single-cell establishment probability to predict each strain's MIC in the absence of social interactions. We observe substantially higher measured than predicted MIC values, particularly for highly resistant strains, which indicates cooperative effects among resistant cells at large cell numbers, such as in standard MIC assays.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Saebelfeld, Manja UNSPECIFIED UNSPECIFIED UNSPECIFIED Das, Suman G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagenbeek, Arno UNSPECIFIED UNSPECIFIED UNSPECIFIED Krug, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED de Visser, J. Arjan G. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-665953
DOI:	10.1098/rspb.2021.2486
Journal or Publication Title:	Proc. R. Soc. B-Biol. Sci.
Volume:	289
Number:	1974
Date:	2022
Publisher:	ROYAL SOC
Place of Publication:	LONDON
ISSN:	1471-2954
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BENEFICIAL MUTATIONS; SPATIAL STRUCTURE; ANTIBIOTICS; EVOLUTION; PROBABILITY; INOCULUM Multiple languages Biology; Ecology; Evolutionary Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66595