Disruption of the Cytoplasmic Membrane Structure and Barrier Function Underlies the Potent Antiseptic Activity of Octenidine in Gram-Positive Bacteria

Abstract

OCT is a well-established antiseptic molecule routinely used in a large field of clinical applications. Since the spread of antimicrobial resistance has restricted the use of antibiotics worldwide, topically applied antiseptics like OCT, with a broad spectrum of antimicrobial activity and high safety profile, gain increasing importance for effective infection prevention and therapy.

Ethanolic Cashew Leaf Extract: Antimicrobial Activity, Mode of Action, and Retardation of Spoilage Bacteria in Refrigerated Nile Tilapia Slices

“…Magnesium ions play a role in peptidoglycan synthesis to strengthen the cell wall and the prevention of cell lysis related to cell viability [ 21 , 45 ]. The permeability of various molecules such as water, nutrients, waste, and ions, is a function of a cytoplasmic membrane that encapsulates bacterial cells [ 46 ]. Several antimicrobial compounds have been found to interact with the cell membrane of the bacterial cytoplasm, causing pores [ 47 ].…”

Octenidine’s Efficacy: A Matter of Interpretation or the Influence of Experimental Setups?

“…We recently reported for the Gram-positive bacterium B. subtilis that OCT induced membrane disorder independently of the magnitude of surface charge or presence of different lipid head groups. Mutants lacking specific head groups were as sensitive to OCT as the wildtype [ 9 , 10 ]. Here, we determined OCT’s antimicrobial activity in mutants of E. coli deficient in the production of major anionic phospholipids CL and PG (BKT12 and BKT29; Table 1 ).…”

“…OCT is a small, synthetic pyridine derivative N,N′-(1,10 decanediyldi-1[4H]-pyridinyl-4-ylidene)-bis-(1- octanamine) dihydrochloride] with a broad spectrum of antimicrobial activity against (multidrug-resistant) bacteria and fungi [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Several studies showed very similar values for minimal inhibitory concentration (MIC) and minimal bacterial concentration (MBC) among different species [ 2 , 9 , 10 ]. Surprisingly, Shepherd et al [ 11 ] reported in 2018 the adaptation of clinical isolates of Pseudomonas aeruginosa to OCT, and Wand et al [ 12 ] described an efflux pump SmvA responsible for OCT tolerance in Klebsiella pneumoniae .…”

“…Moreover, a very recent publication further strengthens the position of OCT with regard to undesired resistance and even cross-resistance to CHG or the last-resort antibiotic colistin in different Enterobacterial species even under high selective pressure in vitro [ 15 ]. In addition, our actual data on the mode of action of OCT on Gram-negative bacteria using Escherichia coli as a model organism [ 10 ] and Gram-positive species using Enterococcus hirae and Bacillus subtilis [ 9 ] underpin membrane disruption as a clear non-specific mechanism. The insertion of OCT into the membrane results in a chaotic lipid arrangement that is not based on specific interaction with the lipid head groups, but strongly affects fatty acyl tails [ 10 ].…”

“…The insertion of OCT into the membrane results in a chaotic lipid arrangement that is not based on specific interaction with the lipid head groups, but strongly affects fatty acyl tails [ 10 ]. We also showed that OCT disrupts membranes composed of any bacterial lipid and further, B. subtilis mutants defective in production of various phospholipids, including pssA and pgsA , are still susceptible to OCT to a similar extent as the wildtype [ 9 ].…”