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Antibiotic Selection00:57

Antibiotic Selection

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Related Experiment Video

Updated: May 9, 2025

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A Dynamic Sugar-Selective Bacterial Nanopore for Targeted Antibiotic Transport.

Sharavanakkumar Sk1, Bibhab Bandhu Majumdar2, Devika Vikraman1

  • 1Transdisciplinary Research Program, BRIC-Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 695014, India.

Small (Weinheim an Der Bergstrasse, Germany)
|May 6, 2025
PubMed
Summary

This study identifies CymAKp, a dynamic bacterial porin from Klebsiella pneumoniae. Its unique gating mechanism regulates sugar and antibiotic transport, offering insights for novel drug delivery systems.

Keywords:
antibioticscyclic sugarsmembrane transportnanoporesporinstargeted‐drug delivery

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Area of Science:

  • Microbiology
  • Biophysics
  • Molecular Biology

Background:

  • Bacterial porins are crucial for nutrient uptake and molecule transport.
  • Their role in pathogenic bacteria and dynamic regulation remains largely unknown.

Purpose of the Study:

  • To identify and characterize a novel monomeric porin, CymAKp, from Klebsiella pneumoniae.
  • To elucidate the structure-function relationship of CymAKp's gating mechanism and its role in selective transport.

Main Methods:

  • Single-channel electrophysiology recordings to analyze nanopore gating.
  • Site-directed mutagenesis to investigate the role of the constricted segment.
  • Molecular dynamics simulations to model translocation pathways.

Main Results:

  • CymAKp exhibits dynamic gating behavior driven by a mobile constricted segment.
  • Deletion of the constricted segment leads to stable nanopores with altered functionality.
  • CymAKp demonstrates sugar selectivity, facilitating cyclic hexasaccharide permeation while excluding larger sugars.
  • Aminoglycoside antibiotics utilize this pathway for translocation, with distinct pathways observed for sugars and antibiotics.

Conclusions:

  • The constricted segment and charged affinity sites are key regulators of CymAKp's dynamic molecular transport.
  • Understanding CymAKp's transport mechanism provides insights for developing targeted nanopore-based drug delivery systems against pathogens.