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Increasing the permeability of Escherichia coli using MAC13243
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17629Article in journal (Refereed) Published
Abstract [en]

The outer membrane of gram-negative bacteria is a permeability barrier that prevents the efficient uptake of molecules with large scaffolds. As a consequence, a number of antibiotic classes are ineffective against gram-negative strains. Herein we carried out a high throughput screen for small molecules that make the outer membrane of Escherichia coli more permeable. We identified MAC13243, an inhibitor of the periplasmic chaperone LolA that traffics lipoproteins from the inner to the outer membrane. We observed that cells were (1) more permeable to the fluorescent probe 1-N-phenylnapthylamine, and (2) more susceptible to large-scaffold antibiotics when sub-inhibitory concentrations of MAC13243 were used. To exclude the possibility that the permeability was caused by an off-target effect, we genetically reconstructed the MAC13243-phenotype by depleting LolA levels using the CRISPRi system.

Place, publisher, year, edition, pages
Macmillan Publishers Ltd., 2017. Vol. 7, article id 17629
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Biochemistry and Molecular Biology
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URN: urn:nbn:se:umu:diva-143193DOI: 10.1038/s41598-017-17772-6ISI: 000418250800014PubMedID: 29247166OAI: oai:DiVA.org:umu-143193DiVA, id: diva2:1167547
Available from: 2017-12-19 Created: 2017-12-19 Last updated: 2018-01-09Bibliographically approved

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