Universität zu Köln

Lukacisinova, Marta, Fernando, Booshini and Bollenbach, Tobias ORCID: 0000-0003-4398-476X (2020). Highly parallel lab evolution reveals that epistasis can curb the evolution of antibiotic resistance. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Genetic perturbations that affect bacterial resistance to antibiotics have been characterized genome-wide, but how do such perturbations interact with subsequent evolutionary adaptation to the drug? Here, we show that strong epistasis between resistance mutations and systematically identified genes can be exploited to control spontaneous resistance evolution. We evolved hundreds of Escherichia coli K-12 mutant populations in parallel, using a robotic platform that tightly controls population size and selection pressure. We find a global diminishing-returns epistasis pattern: strains that are initially more sensitive generally undergo larger resistance gains. However, some gene deletion strains deviate from this general trend and curtail the evolvability of resistance, including deletions of genes for membrane transport, LPS biosynthesis, and chaperones. Deletions of efflux pump genes force evolution on inferior mutational paths, not explored in the wild type, and some of these essentially block resistance evolution. This effect is due to strong negative epistasis with resistance mutations. The identified genes and cellular functions provide potential targets for development of adjuvants that may block spontaneous resistance evolution when combined with antibiotics. The antibiotic resistance crisis calls for new ways of restricting the ability of bacteria to evolve resistance. Here, Lukaiinova et al. perform highly controlled evolution experiments in E. coli strains to identify genetic perturbations that strongly limit the evolution of antibiotic resistance through epistasis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lukacisinova, Marta UNSPECIFIED UNSPECIFIED UNSPECIFIED Fernando, Booshini UNSPECIFIED UNSPECIFIED UNSPECIFIED Bollenbach, Tobias UNSPECIFIED orcid.org/0000-0003-4398-476X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-329507
DOI:	10.1038/s41467-020-16932-z
Journal or Publication Title:	Nat. Commun.
Volume:	11
Number:	1
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Physics > Institut für Biologische Physik
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MULTIDRUG EFFLUX PUMP; ESCHERICHIA-COLI; DRUG-RESISTANCE; BENEFICIAL MUTATIONS; DIMINISHING RETURNS; ACRAB; TOLC; MECHANISMS; INHIBITORS; POTENTIATE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/32950