Abstract:
:Octenidine (OCT) is a widely used antiseptic molecule with an antimicrobial spectrum covering a broad range of bacteria and fungi. However, the detailed molecular mechanism of killing has not yet been elucidated. The objective of our study was to investigate the mode of action of OCT's potent effect on Gram-negative bacteria using Escherichia coli as a model organism as well as corresponding model membranes. The effects of OCT on cellular morphology were observed by electron microscopy, changes affecting membrane integrity (surface charge, fluidity, permeabilisation and depolarisation) by zeta potential, fluorescence microscopy and spectroscopy. Specific interactions of OCT with membrane phospholipids were addressed using differential scanning calorimetry, X-ray scattering and fluorescence techniques. OCT neutralises the surface charge of E. coli leading to disruption of the outer membrane and dramatic loss of the cell wall and further penetrates through the periplasmic space reaching the inner membrane. Model membranes showed that OCT inserts into the hydrophobic fatty acyl chain region of the bilayer, inducing complete lipid disorder. The loss of membrane integrity is also reflected by membrane depolarisation and changes in membrane fluidity as shown by electron microscopy. Insertion of OCT into the outer and inner membrane of E. coli results in a chaotic lipid arrangement that leads to rapid disruption of the cell envelope. We propose that this unspecific mode of action based on purely physical interactions is the basis of the very broad antimicrobial profile and makes it unlikely that resistance to OCT will develop.
journal_name
Int J Antimicrob Agentsjournal_title
International journal of antimicrobial agentsauthors
Malanovic N,Ön A,Pabst G,Zellner A,Lohner Kdoi
10.1016/j.ijantimicag.2020.106146subject
Has Abstractpub_date
2020-11-01 00:00:00pages
106146issue
5eissn
0924-8579issn
1872-7913pii
S0924-8579(20)30344-7journal_volume
56pub_type
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
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