title: Bactericidal Effects and Mechanism of Action of Olanexidine Gluconate, a New Antiseptic.
abstract: Olanexidine gluconate [1-(3,4-dichlorobenzyl)-5-octylbiguanide gluconate] (development code OPB-2045G) is a new monobiguanide compound with bactericidal activity. In this study, we assessed its spectrum of bactericidal activity and mechanism of action. The minimal bactericidal concentrations of the compound for 30-, 60-, and 180-s exposures were determined with the microdilution method using a neutralizer against 320 bacterial strains from culture collections and clinical isolates. Based on the results, the estimated bactericidal olanexidine concentrations with 180-s exposures were 869 μg/ml for Gram-positive cocci (155 strains), 109 μg/ml for Gram-positive bacilli (29 strains), and 434 μg/ml for Gram-negative bacteria (136 strains). Olanexidine was active against a wide range of bacteria, especially Gram-positive cocci, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and had a spectrum of bactericidal activity comparable to that of commercial antiseptics, such as chlorhexidine and povidone-iodine. In vitro experiments exploring its mechanism of action indicated that olanexidine (i) interacts with the bacterial surface molecules, such as lipopolysaccharide and lipoteichoic acid, (ii) disrupts the cell membranes of liposomes, which are artificial bacterial membrane models, (iii) enhances the membrane permeability of Escherichia coli, (iv) disrupts the membrane integrity of S. aureus, and (v) denatures proteins at relatively high concentrations (≥160 μg/ml). These results indicate that olanexidine probably binds to the cell membrane, disrupts membrane integrity, and its bacteriostatic and bactericidal effects are caused by irreversible leakage of intracellular components. At relatively high concentrations, olanexidine aggregates cells by denaturing proteins. This mechanism differs slightly from that of a similar biguanide compound, chlorhexidine.
authors.affiliation: Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan hagia@otsuka.jp.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Hagi
authors.affiliation: Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan.
authors.forename: Koushi
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nii
authors.affiliation: Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nakata
authors.affiliation: Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Tsubotani
authors.affiliation: Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001645:Biguanides / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002710:Chlorhexidine / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D005942:Gluconates / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests / Q000379:methods; D011206:Povidone-Iodine / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D001645:Biguanides; D005942:Gluconates; D011206:Povidone-Iodine; C113749:olanexidine; D002710:Chlorhexidine; C030691:gluconic acid