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The antimicrobial peptide Polybia-MP1 differentiates membranes with the hopanoid, diplopterol from those with

Dayane S Alvares1,2,3, Mariela R Monti2,3, João Ruggiero Neto1

  • 1UNESP - Sao Paulo State University, IBILCE, Department of Physics, São José do Rio Preto, SP, Brazil.

BBA Advances
|April 21, 2023
PubMed

Insights

Antimicrobial peptide Polybia-MP1 activity differs in membranes with cholesterol (CHO) versus hopanoids (diplopterol, DP). DP enhances peptide affinity and alters membrane properties, increasing antimicrobial efficacy against bacteria, suggesting hopanoids influence peptide activity.

Area of Science:

  • Biochemistry
  • Membrane Biophysics
  • Antimicrobial Peptides

Background:

  • Polybia-MP1 (MP1) is an antimicrobial peptide (AMP) with reduced activity in cholesterol-rich membranes.
  • Hopanoids, like diplopterol (DP), function as sterol surrogates in bacteria lacking sterols.
  • Understanding MP1's interaction with DP-containing membranes is crucial for explaining its selective antimicrobial action.

Purpose of the Study:

  • To investigate the impact of diplopterol (DP) on Polybia-MP1 (MP1) activity compared to cholesterol (CHO).
  • To elucidate the biophysical mechanisms underlying MP1-membrane interactions in the presence of DP versus CHO.
  • To assess the role of hopanoids in the antimicrobial efficacy of MP1.

Main Methods:

  • Liposome (LUV) dye release assays to measure membrane permeabilization.
  • Monolayer insertion experiments to assess peptide-membrane binding.
  • Nanotube retraction experiments to evaluate membrane elasticity changes.
  • Zeta potential measurements to analyze surface charge.
  • Antimicrobial activity assays on bacteria incubated with DP or CHO.

Main Results:

  • DP did not inhibit MP1-induced dye release from LUVs, unlike CHO.
  • MP1 showed higher affinity for DP-containing membranes than CHO-containing membranes.
  • DP-containing membranes exhibited complex zeta potential changes and altered elasticity upon MP1 addition.
  • MP1 displayed greater antimicrobial activity against bacteria pre-incubated with DP compared to CHO.

Conclusions:

  • Diplopterol (DP) significantly alters Polybia-MP1 (MP1) membrane interactions, enhancing its activity compared to cholesterol (CHO).
  • The higher antimicrobial efficacy of MP1 against certain bacteria may be attributed to membrane composition, including hopanoids, not just electrostatics.
  • Hopanoids represent a key factor in modulating AMP activity and could be a target for enhancing antimicrobial strategies.
Keywords:
Bacterial resistanceLytic activityMembrane dynamic elasticityOptical tweezersTargeting of AMPsZeta potential

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