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Probing for Thiol-Mediated Uptake into Bacteria.

Quentin Laurent1, Mathéo Berthet1, Yangyang Cheng1

  • 1National Centre of Competence in Research (NCCR), Chemical Biology, School of Chemistry and Biochemistry, University of Geneva, 1211, Geneva, Switzerland.

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|October 12, 2019
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Summary
This summary is machine-generated.

Cyclic oligochalcogenides (COCs) do not facilitate bacterial cell entry. This finding supports sophisticated uptake pathways in mammalian cells, ruling out simple diffusion for COCs.

Keywords:
antibioticscyclic oligochalcogenidesdynamic covalent exchange chemistrythiol-mediated cellular uptake

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Area of Science:

  • Biochemistry
  • Microbiology
  • Cell Biology

Background:

  • Cellular uptake via cyclic oligochalcogenides (COCs) is a novel strategy for mammalian cell penetration.
  • COCs function through dynamic covalent exchange with cellular thiols.

Purpose of the Study:

  • To investigate the efficacy of thiol-mediated uptake by COCs in bacterial cells.
  • To determine if COCs can enhance antibiotic activity in bacteria.

Main Methods:

  • Five antibiotics were modified with cyclic oligochalcogenides (diselenolane, dithiolanes).
  • The modified antibiotics were tested against Gram-negative and Gram-positive bacteria.

Main Results:

  • COCs did not activate antibiotics in Gram-negative bacteria.
  • In Gram-positive bacteria, COCs inactivated cytoplasmic antibiotics and reduced cell surface antibiotic activity.
  • Bacterial membrane thiol interactions did not lead to COC translocation.

Conclusions:

  • Thiol-mediated uptake does not occur across bacterial membranes.
  • The lack of COC uptake in bacteria suggests complex, non-passive entry mechanisms in mammalian cells.