Interaction of cationic antiseptics with cardiolipin-containing model bacterial membranes
https://doi.org/10.47183/mes.2021.024
Abstract
Plasma membrane is one of the major targets for cationic antiseptics (CA). The study was aimed to assess molecular effects of CAs of different chemical classes on cardiolipin-containing regions of bacterial plasma membranes. The study was carried out using coarse-grained molecular modeling. Interaction of CAs, such as miramistin, chlorhexidine, picloxidine, and octenidine, with cardiolipin-containing bilayer was assessed based on the CA coarse-grained models. CAs reduced lipid lateral diffusion coefficients and increased the membrane area per lipid. All CAs, except miramistin, reduced the lipid fatty acid chain order parameters. Adding octenidine at a CA : lipid ratio of 1 : 4 resulted in cardiolipin clustering with subsequent pulling the neutral phosphatidylethanolamine molecules out of the model bilayer. It was found that CАs have the potential for sorption to lipid bilayer, causing clustering of negatively charged lipids. Antiseptic octenidine causes formation of cardiolipin microdomains. Abnormal lateral lipid distribution together with pulling out phosphatidylethanolamine molecules can result in increased lipid bilayer permeability. The most significant reduction of cardiolipin lateral diffusion coefficient by 2.8 ± 0.4 times was observed in the presence of CA chlorhexidine at an antiseptic : lipid ratio of 1 : 4.
Keywords
About the Authors
E. G. KholinaRussian Federation
Orekhovyi bulvar, 28, Moscow, 115682
M. E. Bozdaganyan
Russian Federation
Orekhovyi bulvar, 28, Moscow, 115682
M. G. Strakhovskaya
Russian Federation
Orekhovyi bulvar, 28, Moscow, 115682
I. B. Kovalenko
Russian Federation
Ilya B. Kovalenko
Orekhovyi bulvar, 28, Moscow, 115682
References
1. Denyer SP, Hugo WB. Biocide-induced damage to the bacterial cyctoplasmic membrane. Soc Appl Bacteriol Tech Ser. 1991; 27: 171–87.
2. Kroll RG, Patchett RA. Biocide-induced perturbations of aspects of cell homeostasis : intracellular pH, membrane potential and solute transport. Soc Appl Bacteriol Tech Ser. 1991; 27: 189–202.
3. Russell AD, Hugo WB. Perturbation of homeostatic mechanisms in bacteria by pharmaceuticals. In: Whittenbury R, Gould GW, Banks JG, Board RG, editors. Homeostatic mechanisms in microorganisms. Bath University Press, Bath, England. 1988; р. 206–19.
4. Fuller SJ. Biocide-induced enzyme inhibition. Soc Appl Bacteriol Tech Ser. 1991; 27: 235–49.
5. Kuyyakanond T, Quesnel LB. The mechanism of action of chlorhexidine. FEMS Microbiol Lett Oxford Academic. 1992; 100 (1–3): 211–15.
6. Cheung, HY, Wong MM, Cheung SH, Liang LY, Lam YW, Chiu SK. Differential actions of chlorhexidine on the cell wall of Bacillus subtilis and Escherichia coli. PLoS One. 2012; 7 (5): e36659.
7. Strakhovskaya MG, Khalatyan AS, Budzinskaya MV, Kholina EG, Kolyshkina NA, Kovalenko IB, Zhukhovitsky VG. Chuvstvitel'nost' antibiotikorezistentnyh koagulazonegativnyh stafilokokkov k antiseptiku pikloksidinu. Klinicheskaja praktika. 2020; 11 (1): 42–48. Russian.
8. Gilbert P, Moore LE. Cationic antiseptics: diversity of action under a common epithet. J Appl Microbiol. 2005; 99 (4): 703–15.
9. Dolgushin FM, Goloveshkin AS, Ananyev IV, Osintseva SV, Torubaev YV, Krylov SS, et al. Interplay of noncovalent interactions in antiseptic quaternary ammonium surfactant Miramistin. Acta Crystallogr Sect C International Union of Crystallography (IUCr). 2019; 75 (4): 402–11.
10. Vereshchagin AN, Frolov NA, Egorova KS, Seitkalieva MM, Ananikov VP. Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials. Int J Mol Sci. 2021; 22 (13): 67–93.
11. Van Oosten B, Marquardt D, Komljenović I, Bradshaw JP, Sternin E, Harroun TA. Small molecule interaction with lipid bilayers: a molecular dynamics study of chlorhexidine. J Mol Graph Model. 2014; 48: 96–104.
12. Amsterdam D, Ostrov BE. Disinfectants and antiseptics: Modes of action, mechanisms of resistance, and testing regimens. Antibiotics in Laboratory Medicine. Wolters Kluwer Health Adis (ESP), 2014; p. 1135–230.
13. Lin TY, Weibel DB. Organization and function of anionic phospholipids in bacteria. Appl Microbiol Biotechnol. 2016; 100 (10): 4255–67.
14. Epand RM, Epand RF. Bacterial membrane lipids in the action of antimicrobial agents. J Pept Sci. 2011; 17 (5): 298–305.
15. Matsumoto K, Kusaka J, Nishibori A, Hara H. Lipid domains in bacterial membranes. Mol Microbiol. 2006; 61 (5): 1110–17.
16. Strahl H, Errington J. Bacterial Membranes: Structure, Domains, and Function. Annu Rev Microbiol. 2017; 71: 519–38.
17. Mileykovskaya E, Dowhan W. Cardiolipin membrane domains in prokaryotes and eukaryotes. Biochim Biophys Acta — Biomembr. Elsevier B.V. 2009; 1788 (10): 2084–91.
18. Romantsov T, Battle AR, Hendel JL, Martinac B, Wood JM. Protein localization in Escherichia coli cells: comparison of the cytoplasmic membrane proteins ProP, LacY, ProW, AqpZ, MscS, and MscL. Journal of bacteriology. 2010; 192 (4): 912–24.
19. Camberg JL, Johnson TL, Patrick M, Abendroth J, Hol WG, Sandkvist M. Synergistic stimulation of EpsE ATP hydrolysis by EpsL and acidic phospholipids. The EMBO journal. 2007; 26 (1): 19–27.
20. Kholina EG, Kovalenko IB, Bozdaganyan ME, Strakhovskaya MG, Orekhov PS. Cationic antiseptics facilitate pore formation in model bacterial membranes. The Journal of Physical Chemistry B. 2020; 124 (39): 8593–600.
21. Qi Y, Ingуlfsson HI, Cheng X, Lee J, Marrink SJ, Im W. CHARMMGUI martini maker for coarse-grained simulations with the martini force field. Journal of chemical theory and computation. 2015; 11 (9): 4486–94.
22. Marrink SJ, Risselada HJ, Yefimov S, Tieleman DP, De Vries AH, et al. The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations. J Phys Chem B. 2007; 111 (27): 7812–24.
23. Abraham MJ, Murtola T, Schulz R, Pall S, Smith JC, Hess B, et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. Software X. 2015; 1: 19–25.
24. Yesylevskyy SO, Schäfer LV, Sengupta D, Marrink SJ. Polarizable water model for the coarse-grained MARTINI force field. PLoS computational biology. 2010; 6 (6): e1000810.
25. Singer SJ, Nicolson GL. The Fluid Mosaic Model of the Structure of Cell Membranes. Science. 1972; 175 (4023): 720–31.
26. Macháň R, Hof M. Lipid diffusion in planar membranes investigated by fluorescence correlation spectroscopy. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2010; 1798 (7): 1377–91.
27. Moradi S, Nowroozi A, Shahlaei M. Shedding light on the structural properties of lipid bilayers using molecular dynamics simulation: a review study. RSC Adv. The Royal Society of Chemistry. 2019: 9 (8): 4644–58.
28. John T, Thomas T, Abel B, Wood BR, Chalmers DK, Martin LL. How kanamycin A interacts with bacterial and mammalian mimetic membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2017; 1859 (11): 2242–52.
29. Berglund NA, Piggot TJ, Jefferies D, Sessions RB, Bond PJ, Khalid S. Interaction of the antimicrobial peptide polymyxin B1 with both membranes of E. coli: a molecular dynamics study. PLoS computational biology. 2005; 11 (4): e1004180.
30. Malanovic N, Ön A, Pabst G, Zellner A, Lohner K. Octenidine: Novel insights into the detailed killing mechanism of Gramnegative bacteria at a cellular and molecular level. Int J Antimicrob Agents. 2020; 56 (5): 106146.
Review
For citations:
Kholina E.G., Bozdaganyan M.E., Strakhovskaya M.G., Kovalenko I.B. Interaction of cationic antiseptics with cardiolipin-containing model bacterial membranes. Extreme Medicine. 2021;23(3):38-45. https://doi.org/10.47183/mes.2021.024