Synergistic fungicidal activities of polymyxin B and ionophores, and their dependence on direct disruptive action of polymyxin B on fungal vacuole.
Polymyxin B (PMB) acts selectively on Gram-negative bacteria by electrostatic and hydrophobic interactions with anionic cell envelope components such as phospholipids and lipopolysaccharides. In this study, PMB was shown to exhibit marked fungicidal activity against yeasts and filamentous fungi in combination with ionophores such as salinomycin (SAM) and monensin (MON), which can selectively interact with monovalent cations. Ca(2+)-selective ionophores, A23187 and ionomycin, were absolutely ineffective in enhancing the fungicidal activity of PMB. SAM and MON increased the rate of cellular uptake of PMB possibly in favor of its intracellular action on the organelle. PMB could indeed directly disrupt the spherical membrane-enclosed architecture of the isolated vacuoles equally in the absence and presence of the ionophores. The loss of energy barrier for transmembrane transport of monovalent cations is considered to be a cause of enhanced incorporation of larger cationic compounds such as PMB across fungal plasma membrane.
Ogita
Akira
A
Research Center for Urban Health and Sports, Osaka City University, Sumiyoshi-ku, Osaka, Japan.
Konishi
Yukiko
Y
Borjihan
Baiyinlang
B
Fujita
Ken-ichi
K
Tanaka
Toshio
T
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001234:Aspergillus niger / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D005658:Fungi / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007476:Ionophores / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008985:Monensin / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D011112:Polymyxin B / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011714:Pyrans / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects*; D000095662:Polyether Polyketides
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D007476:Ionophores; D008985:Monensin; D010743:Phospholipids; D011112:Polymyxin B; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides