Fabrication of Bis-Quaternary Ammonium Salt as anEfficient Bactericidal Weapon Against Escherichia coli and Staphylococcus aureus

摘要

Combating bacterial pathogens has become a global concern, especially the emergence of drug-resistant bacteria have made conventional antibiotics lose their efficiency. This grim situation suggests the necessity to explore novel antibacterial agents with favorable safety and strong antibacterial activity. Here, we took the advantage of quaternary ammonium compounds and synthesized a long-chain high-molecular organic bis-quaternary ammonium salt (BQAS) with a broad-spectrum bactericidal activity through a facile one-pot reaction. The bactericidal effect of BQAS was evaluated by two bacterial human pathogens: Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), which are the major cause of diarrheal infections in children and adults. Our experimental results indicate that the bactericidal activity of BQAS is linked to the strong contact between the positively charged quaternary ammonium groups and the bacterial cells, thus leading to a temporary and locally high concentration of reactive oxygen species, which subsequently triggers oxidative stress and membrane damage in the bacteria. This mechanism was further confirmed by several assays, such as the membranepermeabilization assay, fluorescent-based cell live/dead test, scanningelectron microscopy, transmission electron microscopy, together withthe lactate dehydrogenase release assay, which all indicated thatBQAS induced damage to the cytoplasmic membrane and the leakage ofintracellular fluid containing essential molecules. The excellentbactericidal activity of BQAS suggests its great application potentialas a promising candidate against the rapid emergence of drug-resistantbacterial pathogens.