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Inhibiting conjugation as a tool in the fight against antibiotic resistance

Journal article
Authors Fabrice Graf
Martin Palm
Jonas Warringer
Anne Farewell
Published in Drug Development Research
Volume 80
Issue 1
Pages 19-23
ISSN 02724391
Publication year 2018
Published at Department of Chemistry and Molecular Biology
Centre for antibiotic resistance research, CARe
Pages 19-23
Language en
Links https://onlinelibrary.wiley.com/doi...
Keywords antibacterial agents, drug resistance, gene transfer, horizontal, gram-negative bacteria, microbial, plasmids
Subject categories Microbiology, Bacteriology

Abstract

© 2018 Wiley Periodicals, Inc. (Table presented.). Antibiotic resistance, especially in gram-negative bacteria, is spreading globally and rapidly. Development of new antibiotics lags behind; therefore, novel approaches to the problem of antibiotic resistance are sorely needed and this commentary highlights one relatively unexplored target for drug development: conjugation. Conjugation is a common mechanism of horizontal gene transfer in bacteria that is instrumental in the spread of antibiotic resistance among bacteria. Most resistance genes are found on mobile genetic elements and primarily spread by conjugation. Furthermore, conjugative elements can act as a reservoir to maintain antibiotic resistance in the bacterial population even in the absence of antibiotic selection. Thus, conjugation can spread antibiotic resistance quickly between bacteria of the microbiome and pathogens when selective pressure (antibiotics) is introduced. Potential drug targets include the plasmid-encoded conjugation system and the host-encoded proteins important for conjugation. Ideally, a conjugation inhibitor will be used alongside antibiotics to prevent the spread of resistance to or within pathogens while not acting as a growth inhibitor itself. Inhibiting conjugation will be an important addition to our arsenal of strategies to combat the antibiotic resistance crisis, allowing us to extend the usefulness of antibiotics.

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