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Article

Genome-Wide Association Study Reveals Host Factors Affecting Conjugation in Escherichia coli

1
Centre of Microbial and Plant Genetics, KU Leuven, 3001 Leuven, Belgium
2
Center for Microbiology, Flanders Institute for Biotechnology, 3001 Leuven, Belgium
3
IRCAN, CNRS, INSERM, Université Côte d’Azur, 06107 Nice, France
4
Department of Chemistry and Molecular Biology, Centre for Antibiotic Resistance Research, University of Gothenburg, 405 30 Gothenburg, Sweden
*
Author to whom correspondence should be addressed.
Academic Editors: Elisabeth Grohmann and Kornelia Smalla
Microorganisms 2022, 10(3), 608; https://doi.org/10.3390/microorganisms10030608
Received: 28 January 2022 / Revised: 8 March 2022 / Accepted: 10 March 2022 / Published: 12 March 2022
The emergence and dissemination of antibiotic resistance threaten the treatment of common bacterial infections. Resistance genes are often encoded on conjugative elements, which can be horizontally transferred to diverse bacteria. In order to delay conjugative transfer of resistance genes, more information is needed on the genetic determinants promoting conjugation. Here, we focus on which bacterial host factors in the donor assist transfer of conjugative plasmids. We introduced the broad-host-range plasmid pKJK10 into a diverse collection of 113 Escherichia coli strains and measured by flow cytometry how effectively each strain transfers its plasmid to a fixed E. coli recipient. Differences in conjugation efficiency of up to 2.7 and 3.8 orders of magnitude were observed after mating for 24 h and 48 h, respectively. These differences were linked to the underlying donor strain genetic variants in genome-wide association studies, thereby identifying candidate genes involved in conjugation. We confirmed the role of fliF, fliK, kefB and ucpA in the donor ability of conjugative elements by validating defects in the conjugation efficiency of the corresponding lab strain single-gene deletion mutants. Based on the known cellular functions of these genes, we suggest that the motility and the energy supply, the intracellular pH or salinity of the donor affect the efficiency of plasmid transfer. Overall, this work advances the search for targets for the development of conjugation inhibitors, which can be administered alongside antibiotics to more effectively treat bacterial infections. View Full-Text
Keywords: bacterial conjugation; horizontal gene transfer; plasmid; host factors; Escherichia coli; natural isolates; flow cytometry; genome-wide association study; antibiotic resistance; conjugation inhibitors bacterial conjugation; horizontal gene transfer; plasmid; host factors; Escherichia coli; natural isolates; flow cytometry; genome-wide association study; antibiotic resistance; conjugation inhibitors
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MDPI and ACS Style

Van Wonterghem, L.; De Chiara, M.; Liti, G.; Warringer, J.; Farewell, A.; Verstraeten, N.; Michiels, J. Genome-Wide Association Study Reveals Host Factors Affecting Conjugation in Escherichia coli. Microorganisms 2022, 10, 608. https://doi.org/10.3390/microorganisms10030608

AMA Style

Van Wonterghem L, De Chiara M, Liti G, Warringer J, Farewell A, Verstraeten N, Michiels J. Genome-Wide Association Study Reveals Host Factors Affecting Conjugation in Escherichia coli. Microorganisms. 2022; 10(3):608. https://doi.org/10.3390/microorganisms10030608

Chicago/Turabian Style

Van Wonterghem, Laetitia, Matteo De Chiara, Gianni Liti, Jonas Warringer, Anne Farewell, Natalie Verstraeten, and Jan Michiels. 2022. "Genome-Wide Association Study Reveals Host Factors Affecting Conjugation in Escherichia coli" Microorganisms 10, no. 3: 608. https://doi.org/10.3390/microorganisms10030608

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