Quaternary ammonium surfactant structure determines selective toxicity towards bacteria: mechanisms of action and clinical implications in antibacterial prophylaxis

Abstract

Our data show that short chain (C12) n-alkyl pyridinium bromides have a sufficiently large therapeutic window to be good microbicide candidates.

In Vitro Activity of Quaternary Ammonium Surfactants against Streptococcal, Chlamydial, and Gonococcal Infective Agents

“…Three analogous n-alkyl-QAS families, pyridinium bromide (PB), benzyl-dimethylammonium bromide (BZK), and trimethylammonium bromide (TAB), with the same (C 12 ) n-alkyl chain were compared. The reasoning that led to the choice of these analogues has been discussed in previous work (7)(8)(9)11). We show that the studied pathogenic bacteria are much more susceptible to QAS toxic effects than the commensal vaginal bacterial flora and vaginal mucosa cells.…”

“…The MICs for these compounds were also determined for some microorganisms of the commensal vaginal flora. In previous work (7,8,11), we have argued that the effective biocidal concentrations of QAS should be compared after normalization relative to their respective CMC. In what follows, we shall, therefore, compare the efficacy of different QAS using the CMC-normalized MIC (MIC/CMC) values.…”

“…From the perspective of concentration dependence of QAS toxicity, the differences between mammalian and bacterial cells is more pronounced for the short-chain QAS, contrary to what is frequently stated in the literature (10). QAS having n-alkyl groups with 10 to 12 carbons discriminate better between the host cells and the pathogens than do their respective homologues with 14 to 16 carbons (7,8) and offer a sufficiently large therapeutic window to merit research on their use as topical vaginal antiseptics.…”

“…All surfactants are toxic to all cells at concentrations that cause membrane dissolution, but selective toxicity at lower concentrations to bacterial cells, as opposed to mammalian epithelial cells, is observed only for quaternary ammonium surfactants (QAS), a subfamily of the QAC (7,8). We have recently reported detailed studies on the mechanisms of QAS toxicity to mammalian (9) and bacterial (8) cells at concentrations at which cell membrane dissolution does not occur.…”

“…We have recently reported detailed studies on the mechanisms of QAS toxicity to mammalian (9) and bacterial (8) cells at concentrations at which cell membrane dissolution does not occur. Our results indicated that while QAS toxicity to mammalian cells was primarily due to surfactant-induced mitochondrial dysfunction (9), the toxic action on bacteria was considerably more complex (8), involving impairment of bacterial energetics and cell division at low concentrations and membrane permeabilization and electron transport inhibition at slightly higher doses. From the perspective of concentration dependence of QAS toxicity, the differences between mammalian and bacterial cells is more pronounced for the short-chain QAS, contrary to what is frequently stated in the literature (10).…”