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Emergence of Resistant Escherichia coli Mutants in Microfluidic On-Chip Antibiotic Gradients

Nagy, Krisztina and Dukic, Barbara and Hodula, Orsolya and Ábrahám, Ágnes and Csákvári, Eszter and Dér, László and Wetherington, Miles T and Galajda, Péter (2022) Emergence of Resistant Escherichia coli Mutants in Microfluidic On-Chip Antibiotic Gradients. FRONTIERS IN MICROBIOLOGY, 13. ISSN 1664-302X

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Abstract

Spatiotemporal structures and heterogeneities are common in natural habitats, yet their role in the evolution of antibiotic resistance is still to be uncovered. We applied a microfluidic gradient generator device to study the emergence of resistant bacteria in spatial ciprofloxacin gradients. We observed biofilm formation in regions with sub-inhibitory concentrations of antibiotics, which quickly expanded into the high antibiotic regions. In the absence of an explicit structure of the habitat, this multicellular formation led to a spatial structure of the population with local competition and limited migration. Therefore, such structures can function as amplifiers of selection and aid the spread of beneficial mutations. We found that the physical environment itself induces stress-related mutations that later prove beneficial when cells are exposed to antibiotics. This shift in function suggests that exaptation occurs in such experimental scenarios. The above two processes pave the way for the subsequent emergence of highly resistant specific mutations.

Item Type: Article
Additional Information: Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Fund [OTKA PD 124889, K 116516]; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-20-5-SZTE-658]; Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences [BO/00463/18/8]; Hungarian Government; European Regional Development FundEuropean Commission [GINOP-2.3.2-15-2016-00001, GINOP-2.3.2-15-2016-00026, GINOP-2.3.2-15-2016-00037]; James S. McDonnell Foundation Postdoctoral Fellowship award; Chilean National Agency for Science and Innovation (ANID) [CONICYT FONDECYT 1191893]; Millennium Science Initiative Program (ANID Chile) [NCN19_170] Funding text: KN and PG acknowledge the support of the Hungarian National Research, Development and Innovation Fund under Grant Numbers OTKA PD 124889, K 116516, and the UNKP-20-5-SZTE-658 New National Excellence Program of the Ministry for Innovation and Technology. KN was also supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00463/18/8). Furthermore, this work was supported by the Hungarian Government and the European Regional Development Fund under the Grant Numbers GINOP-2.3.2-15-2016-00001, GINOP-2.3.2-15-2016-00026, and GINOP-2.3.2-15-2016-00037. MW gratefully acknowledges support from the James S. McDonnell Foundation Postdoctoral Fellowship award. JK and JN acknowledge funding from the Chilean National Agency for Science and Innovation (ANID), under Grant Number CONICYT FONDECYT 1191893. JK was also supported by the Millennium Science Initiative Program-NCN19_170 (ANID Chile).
Uncontrolled Keywords: IDENTIFICATION; MUTATIONS; TOLERANCE; EVOLUTION; EVOLUTION; biosynthesis; MOLECULAR-MECHANISMS; motility; Antibiotic resistance; Microfluidics; disulfide bond formation; antibiotic gradients;
Subjects: Q Science / természettudomány > QR Microbiology / mikrobiológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 21 Sep 2022 09:58
Last Modified: 21 Sep 2022 09:58
URI: http://real.mtak.hu/id/eprint/149203

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