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Cross-Resistance to Antibiotics After Exposure to Qaternary Ammonium Compounds
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.ORCID iD: 0000-0001-6640-2174
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Quaternary ammonium compounds (QACs) are common antimicrobials that are used in a variety of consumer products, such as lotions, sunscreen, hair conditioners and hand sanitizers, to inhibit bacterial growth. However, it has been noted that bacteria exposed to QACs can develop resistance, and additionally, resistance to QACs has been observed to provide cross-resistance to antibiotics. In order to identify genetic adaptations for this resistance pattern, we exposed E. coli to three different QACs at sub-MIC and above-MIC concentrations, and identified genetic changes by whole genome sequencing. We found that initial adaptation, at sub-MIC levels, happened through efflux mechanisms, and that subsequent genetic changes, during above-MIC exposure, involved genes associated with the cell membranes and with transcription/translation. We also found that these genetic changes provided cross-resistance to other QACs as well as to several antibiotics.

Keywords [en]
Antibiotic resistance, Antimicrobials, Cross-resistance
National Category
Other Medical Sciences not elsewhere specified
Identifiers
URN: urn:nbn:se:uu:diva-356967OAI: oai:DiVA.org:uu-356967DiVA, id: diva2:1237658
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-10
In thesis
1. Antibiotic Resistance: Selection in the Presence of Metals and Antimicrobials
Open this publication in new window or tab >>Antibiotic Resistance: Selection in the Presence of Metals and Antimicrobials
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The external environment is complex: Antibiotics, metals and antimicrobials do not exist in isolation but in mixtures. Human activities such as animal husbandry, fertilization of agricultural fields and human medicine release high amounts these compounds into the environment. The work in this thesis contributes to our understanding of how the selection of bacterial antibiotic resistance can be facilitated by the pollution by metals and antimicrobials. We show that low levels of antibiotics, metals and combinations thereof can lead to the selection of chromosomally encoded antibiotic resistance genes as well as a multidrug resistance plasmid. The underlying genetic and cellular mechanisms of selection identified relate to mutational changes in a plasmid-encoded metal resistance operon, and metal-associated increases in cellular membrane permeability. We further show that exposure to quaternary ammonium compounds can result in cross-resistance to antibiotics following genetic changes in genes related to efflux, membrane synthesis and transcription/translation. Taken together, the work in this thesis suggests that the stewardship of antibiotics should include prudent use of metals and antimicrobials. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 53
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1488
Keywords
Antibiotic resistance, Metals, Antimicrobials, Bacterial evolution, Bacterial genetics
National Category
Microbiology Genetics Evolutionary Biology
Research subject
Biology with specialization in Microbiology
Identifiers
urn:nbn:se:uu:diva-356970 (URN)978-91-513-0412-0 (ISBN)
Public defence
2018-10-05, B42, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2018-09-14 Created: 2018-08-10 Last updated: 2018-10-02

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