Serine-based surfactants as effective antimicrobial agents against multiresistant bacteria

Area of Science:

• * Medicinal Chemistry
• * Antimicrobial Agents
• * Biomaterials

Background:

• * The rise of antibiotic-resistant bacteria necessitates the development of novel antimicrobial agents.
• * Cationic surfactants, particularly gemini surfactants, have emerged as promising candidates due to their potent antimicrobial properties.
• * Serine-derived surfactants offer a potentially biocompatible and tunable platform for antimicrobial drug discovery.

Purpose of the Study:

• * To synthesize and evaluate the antimicrobial activity of two serine-derived gemini cationic surfactants: amide ((12Ser)₂CON12) and ester ((12Ser)₂COO12).
• * To investigate the interaction of these surfactants with model lipid membranes and their effect on bacterial membranes.
• * To assess the cytotoxicity of the synthesized compounds on human red blood cells.

Main Methods:

• * Antimicrobial activity testing using minimum inhibitory concentration (MIC) assays against sensitive and resistant strains of *E. coli* and *S. aureus*.
• * Investigation of surfactant-lipid interactions using Langmuir monolayers with dipalmitoylphosphatidylglycerol (DPPG) and dipalmitoylphosphatidylcholine (DPPC).
• * Atomic Force Microscopy (AFM) to visualize the effects of surfactants on bacterial membrane integrity.
• * Hemolysis assays to determine the cytotoxicity of the compounds on human red blood cells (RBCs).

Main Results:

• * Both amide and ester derivatives exhibited significant antimicrobial activity, with very low MIC values (5 μM) against resistant strains *E. coli* TEM CTX M9 and *S. aureus* MRSA ATCC 43300.
• * The surfactants showed a more pronounced effect on DPPG lipid monolayers compared to DPPC monolayers.
• * AFM revealed clear disruption of the *E. coli* TEM CTX M9 membrane by the amide derivative ((12Ser)₂CON12).
• * The compounds demonstrated non-cytotoxicity up to 10 μM on human red blood cells.

Conclusions:

• * The serine-derived gemini cationic surfactants, particularly the amide derivative, show significant potential as antimicrobial agents against antibiotic-resistant bacteria.
• * The mechanism of action involves disruption of bacterial membranes, with varying effects observed on different bacterial strains and lipid compositions.
• * The low cytotoxicity suggests a favorable safety profile for potential therapeutic applications.