Action of Reactive Oxygen Species in the Antifungal Mechanism of Gemini-pyridinium Salts Against Yeast

• Published in: Biocontrol Science Vol. 17; no. 2; pp. 77 - 82
• Main Authors: SHIRAI, AKIHIRO, UETA, SHOUKO, MASEDA, HIDEAKI, KOURAI, HIROKI, OMASA, TAKESHI
• Format: Journal Article
• Language: English
• Published: Japan The Society for Antibacterial and Antifungal Agents, Japan 2012; Japan Science and Technology Agency
• Subjects: Aerobic conditions; Aerobiosis; Anaerobic conditions; Anaerobiosis; Antifungal activity; Antifungal Agents - pharmacology; Antimicrobial activity; Antimicrobial agents; Biological control; Candida albicans; Candida albicans - drug effects; Candida albicans - metabolism; Catalase; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Respiration - drug effects; Cell survival; Cell Wall - drug effects; Cell Wall - metabolism; Chloride; Drug Synergism; Free Radical Scavengers - pharmacology; Fungicidal activity; Gemini-pyridinium salt; Ions; Leakage; Magnesium; Microbial Sensitivity Tests; Nitrogen; Oxidative stress; Oxidative Stress - drug effects; potassium iodide; pyridinium; Pyridinium Compounds - pharmacology; Quaternary Ammonium Compounds - pharmacology; Reactive oxygen species; Reactive Oxygen Species - pharmacology; Saccharomyces cerevisiae; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - metabolism; Salts; Superoxide dismutase; Time Factors; Yeast
• ISSN: 1342-4815; 1884-0205
• DOI: 10.4265/bio.17.77

We previously found that the gemini quaternary salt (gemini-QUAT) containing two pyridinium residues per molecule, 3,3'- (2,7-dioxaoctane) bis (1-decylpyridinium bromide) (3DOBP-4,10) , exerted fungicidal activity against Saccharomyces cerevisiae and caused respiration inhibition and the cytoplasmic leakage of ATP, magnesium, and potassium ions. Here, we investigated how the gemini-QUAT, 3DOBP-4,10, exerts more powerful antimicrobial activity than the mono-QUAT N-cetylpyridinium chloride (CPC) and examined the association between reactive oxygen species (ROS) and the antimicrobial mechanism. Antifungal assays showed that the activity of 3DOBP-4,10 against two yeasts, S. cerevisiae and Candida albicans, was significantly elevated under aerobic conditions, and largely reduced under anaerobic conditions (nitrogen atmosphere) . Adding radical scavengers such as superoxide dismutase, catalase and potassium iodide (KI) also decreased the fungicidal activity of 3DOBP-4,10 but negligibly affected that of CPC. We measured survival under static conditions and found that the rapid fungicidal profile of 3DOBP-4,10 was lost, whereas that of CPC was slightly affected in the presence of KI. Our results suggest that 3DOBP-4,10 exerts powerful antimicrobial activity by penetrating the cell wall and membrane, which then allows oxygen to enter the cells, where it participates in the generation of intracellular ROS. The activity could thus be attributable to a synergic antimicrobial combination of the disruption of organelle membranes by the QUAT and oxidative stress imposed by ROS.