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Novel Amiloride Derivatives That Inhibit Bacterial Motility across Multiple Strains and Stator Types.

M I Islam1, J H Bae1, T Ishida2

  • 1School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.

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|September 13, 2021
PubMed
Summary

Two novel amiloride derivatives, HM2-16F and BB2-50F, effectively inhibit bacterial flagellar motors. These compounds target both proton and sodium-driven motility across various bacterial strains, offering new antimicrobial strategies.

Keywords:
amilorideantimicrobial agentsbacterial flagellar motorbacterial motilityflagellar motilityion channelsmotilitysodium channel blockerstatorvirulence

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Area of Science:

  • Microbiology
  • Biochemistry
  • Molecular Biology

Background:

  • The bacterial flagellar motor (BFM) drives cell motility, crucial for survival and virulence.
  • BFM rotation is powered by ion gradients, primarily protons (H+) and sodium ions (Na+).
  • Phenamil is a known inhibitor of sodium-powered stators, but new inhibitors are scarce.

Purpose of the Study:

  • To characterize two amiloride derivatives, HM2-16F and BB2-50F, as potential inhibitors of bacterial flagellar motility.
  • To investigate their mechanism of action and efficacy against different BFM types and bacterial strains.

Main Methods:

  • Assessing the effect of HM2-16F and BB2-50F on the rotation of tethered cells.
  • Observing the impact on free-swimming bacteria.
  • Measuring the rotation of marker beads to elucidate the inhibition mechanism.

Main Results:

  • HM2-16F and BB2-50F inhibited both Na+- and H+-driven flagellar motors at 10 μM.
  • The compounds demonstrated broad efficacy against pathogenic and nonpathogenic strains, including *Escherichia coli* and *Vibrio alginolyticus*.
  • Inhibition did not result from direct interaction with stator complexes, unlike phenamil.

Conclusions:

  • HM2-16F and BB2-50F are effective broad-spectrum inhibitors of bacterial flagellar motility.
  • These compounds represent promising novel antimotility agents for controlling bacterial pathogens.
  • Their distinct mechanism offers new avenues for antimicrobial drug development.