Bacterioclastic Action of a Bis-Quaternary Ammonium Compound against Escherichia coli

  • SUMITOMO TOMOKO
    Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima
  • MAEDA TAKUYA
    Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima
  • NAGAMUNE HIDEAKI
    Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima
  • KOURAI HIROKI
    Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima

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It has been reported that the bactericidal action of bis-quaternary ammonium compounds (bis-QACs) is little influenced by the molecular hydrophobicity. of the drug or environmental conditions such as temperature or pH. In order to clarify the mode of bactericidal action of bis-QACs against Escherichia coli, the bacterioclastic action of 4, 4'-(1, 6-hexamethylenedithio) bis (1-octylpyridinium bromide) (4DTBP-6, 8) was investigated. It was suggested that 4DTBP-6, 8, which invaded the bacterial cell, induced the leakage of ATP and the inhibition of the respiratory enzymes, and resulted in cell death. Subsequently, over 2μg/ml of4DTBP-6, 8 caused an increase in the turbidity of the cell suspension, and the bactericidal activity of 4DTBP-6, 8 was extremely increased with the increase of its concentration (over 2μg/ml). It indicated that 4DTBP-6, 8 has an ability to induce a rapid and abundant secretion of the turbid materials from the cells and that such bacterioclastic ability is connected to its potent bactericidal activity. In addition, it was suggested that the first stage of bacterioclastic action of 4DTBP-6, 8 was the leakage of magnesium ion (Mg2+), and the leakage of the outer membrane pore protein E and lipopolysaccharides followed it. The formation of blebs and holes on the bacterial cell surface was revealed by scanning electron microscopic investigation. Transmission electron micrographs of the cells treated with 4DTBP-6, 8 showed the destruction of peptidoglycan and large missing portions of intercellular materials. Judging from these results, as the mechanism of the bacterioclastic action of bis-QACs, it is suggested that the cationic parts of bis-QACs electrically interact with the cationic parts of Mg2+ on the bacterial surface, then bis-QACs invade the cell membrane by displacement reaction with Mg2+, and rapidly destroy the bacterial cell surface structure.

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