Department of Microbiology and Immunology, Emory University, 30322, Atlanta, GA, USA.
Department of Chemistry, Emory University, 30322, Atlanta, GA, USA.
ChemMedChem. 2024 Aug 19;19(16):e202400262. doi: 10.1002/cmdc.202400262. Epub 2024 Jul 4.
Quaternary ammonium compound (QAC) disinfectants represent one of our first lines of defense against pathogens. Their inhibitory and bactericidal activities are usually tested through minimum inhibitory concentration (MIC) and time-kill assays, but these assays can become cumbersome when screening many compounds. We investigated how the dynamic surface tension (DST) measurements of QACs correlate with these antimicrobial activities by testing a panel of potent and structurally varied QACs against the gram-positive Staphylococcus aureus and the gram-negative Pseudomonas aeruginosa. We found that DST values correlated well with bactericidal activity in real-world disinfection conditions but not with MIC values. Moreover, no correlation between these two antimicrobial activities of QACs (bactericidal and inhibition) was observed. In addition, we observed that the bactericidal activity of our QAC panel against the gram-negative P. aeruginosa was severely affected in the presence of hard water. Interestingly, we found that the counterion of the QAC affects the killing of bacteria in these conditions, a phenomenon not observed in most MIC assessments. Moreover, some of our best-in-class QACs show enhanced bactericidal activity when combined with a commercially available QAC. In conclusion, we determined that an intrinsic physical property of QACs (DST) can be used as a technique to screen for bactericidal activity of QACs in conditions that mimic real-world disinfection conditions.
季铵化合物 (QAC) 消毒剂是我们抵御病原体的第一道防线之一。它们的抑制和杀菌活性通常通过最小抑菌浓度 (MIC) 和杀菌时间试验进行测试,但在筛选大量化合物时,这些试验可能会变得繁琐。我们通过测试一系列有效且结构多样的 QAC 对革兰氏阳性金黄色葡萄球菌和革兰氏阴性铜绿假单胞菌,研究了 QAC 的动态表面张力 (DST) 测量值与这些抗菌活性之间的相关性。我们发现,在实际消毒条件下,DST 值与杀菌活性相关性良好,但与 MIC 值无关。此外,QAC 的这两种抗菌活性(杀菌和抑制)之间没有相关性。此外,我们观察到我们的 QAC 对革兰氏阴性铜绿假单胞菌的杀菌活性在硬水存在下受到严重影响。有趣的是,我们发现 QAC 的反离子会影响这些条件下细菌的杀灭,而在大多数 MIC 评估中并未观察到这种现象。此外,我们一些最佳类别的 QAC 与市售 QAC 结合使用时显示出增强的杀菌活性。总之,我们确定了 QAC 的内在物理特性(DST)可用作在模拟实际消毒条件下筛选 QAC 杀菌活性的技术。