Insight into the Antibacterial Activities of Pyridinium-Based Cationic Pillar[5]arene with Controllable Hydrophobic...

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Antimicrobial Research

Background:

• Rising infections from pathogenic bacteria, particularly Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), pose a significant global health threat.
• Pillar[5]arenes with functional groups demonstrate potential antimicrobial and anti-biofilm properties, necessitating investigation into structure-activity relationships.
• Understanding the balance between antimicrobial efficacy and cytotoxicity is crucial for developing safe and effective antibacterial agents.

Purpose of the Study:

• To synthesize and characterize novel pyridinium-based cationic pillar[5]arenes (PPs) with varying hydrophobic chain lengths.
• To evaluate the antimicrobial activity, antibiofilm potential, and cytotoxicity of the synthesized PPs against Staphylococcus aureus.
• To elucidate the mechanism of action of PPs on bacterial membranes.

Main Methods:

• Synthesis and systematic characterization of four pyridinium-based cationic pillar[5]arenes with linear aliphatic chains of differing lengths.
• Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Staphylococcus aureus (ATCC 6538).
• Assessment of antibiofilm activity, antimicrobial resistance development, and investigation of membrane interaction using transmission electron microscopy (TEM).

Main Results:

• PP6, featuring six methylenes in its linker, demonstrated potent inhibition of Staphylococcus aureus with an MIC of 3.91 μg/mL and MBC of 62.50 μg/mL.
• PP6 exhibited superior antibiofilm capabilities and negligible antimicrobial resistance, even after 20 passages.
• TEM analysis revealed that PPs induce bacterial membrane depolarization and lysis by inserting cationic pyridine groups into the negatively charged bacterial membrane, leading to leakage and cell death.
• All synthesized PPs displayed very low toxicity towards mammalian cells (L929 and HBZY-1).

Conclusions:

• Pyridinium-based cationic pillar[5]arenes, particularly PP6, are effective against Staphylococcus aureus and possess strong antibiofilm properties.
• The mechanism involves direct interaction with and disruption of the bacterial membrane.
• The low cytotoxicity of these compounds makes them promising candidates for developing novel, hypotoxic antibacterial biomaterials against multidrug-resistant bacteria.