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  3. Increasing the permeability of Escherichia coli using MAC13243

Increasing the permeability of Escherichia coli using MAC13243

  • Sci Rep. 2017 Dec 15;7(1):17629. doi: 10.1038/s41598-017-17772-6.
Claudio Muheim 1,  Hansjörg Götzke 1,  Anna U Eriksson 2,  Stina Lindberg 2,  Ida Lauritsen 3,  Morten H H Nørholm 3,  Daniel O Daley 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Biophysics Stockholm University, Stockholm, Sweden.
  • 2 Chemical Biology Consortium Sweden, Laboratories for Chemical Biology, Umeå University, Umeå, Sweden.
  • 3 Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs., Lyngby, Denmark.
  • 4 Department of Biochemistry and Biophysics Stockholm University, Stockholm, Sweden. ddaley@dbb.su.se.
PMID: 29247166 DOI: 10.1038/s41598-017-17772-6
Abstract

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.

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