Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives.

Area of Science:

• Biochemistry
• Materials Science
• Microbiology

Background:

• Antimicrobial peptides are crucial for combating drug-resistant bacteria.
• Disrupting bacterial membranes is a key mechanism for antimicrobial action.
• Developing synthetic peptide mimics offers a promising therapeutic avenue.

Purpose of the Study:

• To investigate a novel cyclodextrin-based scaffold as a peptide mimic for antibacterial applications.
• To synthesize and characterize polyfunctionalized cyclodextrins with simplified antibacterial moieties.
• To evaluate the membrane-disrupting activity and antibacterial efficacy of these compounds.

Main Methods:

• Chemical synthesis of polyfunctionalized cyclodextrins using a poly-click reaction.
• Assessment of antibacterial activity against Gram-positive and Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae.
• High-speed atomic force microscopy (HS-AFM) for direct visualization of membrane disruption.
• Evaluation of synergistic effects with traditional antibiotics.

Main Results:

• Cyclodextrins functionalized with eight alkylamino groups demonstrated broad-spectrum antibacterial activity.
• These compounds effectively disrupted bacterial membranes, leading to rapid cell death.
• HS-AFM confirmed direct membrane perturbation.
• Enhanced efficacy of traditional antibiotics against Gram-negative bacteria when co-administered.

Conclusions:

• Polyfunctionalized cyclodextrins serve as effective membrane-disrupting antibacterial agents.
• This approach shows potential for treating infections caused by drug-resistant pathogens.
• The synergistic effect with antibiotics broadens therapeutic possibilities.