Action of reactive oxygen species in the antifungal mechanism of gemini-pyridinium salts against yeast.
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.
Department of Biological Science and Technology, Biosystems Engineering, Institute of Technology and Science, The University of Tokushima, Tokushima, Japan.
Akihiro
A
Shirai
Shouko
S
Ueta
Hideaki
H
Maseda
Hiroki
H
Kourai
Takeshi
T
Omasa
D000332:Aerobiosis; D000693:Anaerobiosis; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress / Q000187:drug effects; D011726:Pyridinium Compounds / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
C540860:3,3'-(2,7-dioxaoctane)bis(1-decylpyridinium); D000935:Antifungal Agents; D016166:Free Radical Scavengers; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D017382:Reactive Oxygen Species