Paper MB+BI-ThM11
Mechanisms of Antimicrobial Activity of Quaternary Ammonium Compounds in Solution and Immobilized on a Surface

Thursday, November 1, 2012, 11:20 am, Room 23

Quaternary ammonium compounds (QAC) are potent cationic antimicrobials used in everyday consumer products like contact lens solutions and mouthrinses as well as in numerous industrial processes, like water purification. Unlike the case for many antibiotics, the development of bacterial resistance against QACs is considered unlikely, although Pseudomonas aeruginosa strains isolated from contact lens cases have been shown to possess resistance against QACs. The first step in the antimicrobial action of QACs is the approach of the QAC molecule towards the bacterial cell surface. This is mediated by hydrophobic and electrostatic attractions between positively charged QAC molecules and the negatively charged bacterial cell surface. Upon their subsequent adsorption, QAC molecules replace Ca²⁺ or Mg²⁺ ions from the cytoplasmic membrane in order to maintain charge neutrality in the membrane. The replacement of Ca²⁺ and Mg²⁺ ions by QACs destabilizes the intracellular matrix of a bacterium, as the hydrophobic tail interdigitates into the hydrophobic bacterial membrane causing leakage of intracellular fluid and loss of turgor pressure. Antimicrobial efficacy of QACs remains preserved when QAC molecules are immobilized on a substratum surface. It is difficult to envisage how immobilized QAC molecules can exert the same mechanism of antimicrobial activity as do QACs in solution. Immobilized QACs, especially after adsorption of a protein film as developing rapidly in the human body, are strongly hindered in their search for heterogeneously distributed negative charges on bacterial cell surfaces which is crucial for their efficacy in solution. Hence, it has been often hypothesized that QAC molecules immobilized to a substratum surface possess other generic mechanisms of action than QACs in solution, but these have never been elucidated. Immobilized QACs do not cause directly visual membrane damage. Instead, the strong adhesion forces arising from immobilized QACs enter bacterial adhesion forces into the lethal regime, i.e. where the stress exerted on the bacterial cell membrane is causing killing.