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Proton Motive Force Disruptors Block Bacterial Competence and Horizontal Gene Transfer.
Journal article

Proton Motive Force Disruptors Block Bacterial Competence and Horizontal Gene Transfer.

  • Domenech A Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen 9747AG, the Netherlands; Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, Lausanne 1015, Switzerland.
  • Brochado AR European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany.
  • Sender V Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden.
  • Hentrich K Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden.
  • Henriques-Normark B Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden; Department of Clinical Microbiology, Karolinska University Hospital Solna, Stockholm 171 76, Sweden.
  • Typas A European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany.
  • Veening JW Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen 9747AG, the Netherlands; Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, Lausanne 1015, Switzerland. Electronic address: jan-willem.veening@unil.ch.
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  • 2020-03-05
Published in:
  • Cell host & microbe. - 2020
DNA uptake
Streptococcus pneumoniae
antibiotic resistance
competence development
horizontal gene transfer
transformation
English Streptococcus pneumoniae is a commensal of the human nasopharynx that can also cause severe antibiotic-resistant infections. Antibiotics drive the spread of resistance by inducing S. pneumoniae competence, in which bacteria express the transformation machinery that facilitates uptake of exogenous DNA and horizontal gene transfer (HGT). We performed a high-throughput screen and identified potent inhibitors of S. pneumoniae competence, called COM-blockers. COM-blockers limit competence by inhibiting the proton motive force (PMF), thereby disrupting export of a quorum-sensing peptide that regulates the transformation machinery. Known chemical PMF disruptors and alterations in pH homeostasis similarly inhibit competence. COM-blockers limit transformation of clinical multi-drug-resistant strains and HGT in infected mice. At their active concentrations, COM-blockers do not affect growth, compromise antibiotic activity, or elicit detectable resistance. COM-blockers provide an experimental tool to inhibit competence and other PMF-involved processes and could help reduce the spread of virulence factors and antibiotic resistance in bacteria. VIDEO ABSTRACT.
Language
  • English
Open access status
closed
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Persistent URL
https://sonar.ch/global/documents/278062
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