Antibacterial Activity of 1-Dodecylpyridinium Tetrafluoroborate and Its Inclusion Complex With Sulfobutyl Ether-β-Cyclodextrin Against MDR Acinetobacter baumannii Strains
DOI:
https://doi.org/10.20535/ibb.2023.7.4.288529Keywords:
cationic biocide, antibacterial activity, acute toxicity, molecular docking, β-cyclodextrin, inclusion complexAbstract
Background. The bacterial pathogen Acinetobacter baumannii is one of the most dangerous multi-drug-resistant (MDR) microorganisms, which causes numerous bacterial infections. Nowadays, there is an urgent need for new broad-spectrum antibacterial agents with specific molecular mechanisms of action. Long-chain 1-alkylpyridinium salts are efficient cationic biocides which can inhibit enzymes involved in the biosynthesis of bacterial fatty acids. Incorporating these compounds into inclusion complexes with cyclic oligosaccharide β-cyclodextrin can reduce their relatively high acute toxicity.
Objective. The aim of this research was to develop new anti-A. baumannii agents based on hydrophobic 1-alkylpyridinium salt and its inclusion complex with sulfobutyl ether b-cyclodextrin (SBECD).
Methods. Hydrophobic cationic biocide 1-dodecylpyridinium tetrafluoroborate (PyrC12-BF4) and its inclusion complex with SBECD have been synthesized. The structure of the SBECD/PyrC12-BF4 complex was characterized by 1H Nuclear Magnetic Resonance spectroscopy, as well as UV spectroscopy. In vitro antibacterial activity of the synthesized compounds was estimated against MDR clinical isolates of A. baumannii using standard disc diffusion method. Acute toxicity studies were performed on Daphnia magna model hydrobiont. Molecular docking was performed using the crystal structure of the A. baumannii 3-oxoacyl-[acyl-carrier-protein] reductase (FabG).
Results. The results of 1H NMR study revealed the formation of an inclusion complex between SBECD and PyrC12-BF4. The cationic biocide demonstrated high activity against four tested antibiotic-resistant strains of A. baumannii, whereas the SBECD/PyrC12-BF4 complex was active against only two bacterial strains. Molecular docking of 1-dodecylpyridinium ligand into the active site of the A. baumannii (FabG) showed complex formation at an allosteric site located between subunits C, D. The acute toxicity (LC50) of PyrC12-BF4 and its inclusion complex was found to be 0.007 and 0.033 ml/g, respectively.
Conclusions. Hydrophobic cationic biocide PyrC12-BF4 has high antibacterial activity against MDR A. baumannii. The inhibition of the active site FabG may be one of the possible mechanisms of anti-A. baumannii activity of the PyrC12-BF4. The SBECD/PyrC12-BF4 inclusion complex showed an almost 5-fold reduction in acute toxicity compared to PyrC12-BF4, while retaining activity against certain tested A. baumannii bacterial strains.
References
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 Jun 24;22(13):6793. DOI: 10.3390/ijms22136793
Morais DS, Guedes RM, Lopes MA. Antimicrobial approaches for textiles: from research to market. Materials (Basel). 2016 Jun 21;9(6):498. DOI: 10.3390/ma9060498
Hora PI, Pati SG, McNamara PJ, Arnold WA. Increased use of quaternary ammonium compounds during the SARS-Cov-2 pandemic and beyond: consideration of environmental implications. Environ Sci Technol Lett. 2020 Jun 26;7(9):622-31. DOI: 10.1021/acs.estlett.0c00437
Gonҫalves RA, Holmberg K, Lindman B. Cationic surfactants: a review. J Mol Liq. 2023;375:121335. DOI: 10.1016/j.molliq.2023.121335
Gilbert P, Moore LE. Cationic antiseptics: diversity of action under a common epithet. J Appl Microbiol. 2005;99(4):703-15. DOI: 10.1111/j.1365-2672.2005.02664.x
Zhou C, Wang Y. Structure-activity relationship of cationic surfactants as antimicrobial agents. Curr Opin Colloid Interf. 2020;45:28-43. DOI: 10.1016/j.cocis.2019.11.009
Pérez L, García MT, Pinazo A, Pérez-Matas E, Hafidi Z, Bautista E. Cationic surfactants based on arginine-phenylalanine and arginine-tryptophan: synthesis, aggregation behavior, antimicrobial activity, and biodegradation. Pharmaceutics. 2022 Nov 25;14(12):2602. DOI: 10.3390/pharmaceutics14122602
Mao X, Auer DL, Buchalla W, Hiller KA, Maisch T, Hellwig E, et al. Cetylpyridinium chloride: mechanism of action, antimicrobial efficacy in biofilms, and potential risks of resistance. Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00576-20. DOI: 10.1128/AAC.00576-20
Ishikawa S, Matsumura Y, Yoshizako F, Tsuchido T. Characterization of a cationic surfactant-resistant mutant isolated spontaneously from Escherichia coli. J Appl Microbiol. 2002;92(2):261-8. DOI: 10.1046/j.1365-2672.2002.01526.x
Kalpana S, Lin WY, Wang YC, Fu Y, Lakshmi A, Wang HY. Antibiotic resistance diagnosis in ESKAPE pathogens-A review on proteomic perspective. Diagnostics (Basel). 2023 Mar 7;13(6):1014. DOI: 10.3390/diagnostics13061014
The world is running out of antibiotics, WHO report confirms [Internet]. World Health Organization. 2017 [cited 2023 Jul 17]. Available from: http://www.who.int/mediacentre/news/releases/2017/running-out-antibiotics/en/
Merli M, D'Amico F, Travi G, Puoti M. Current state of antimicrobial treatment of lower respiratory tract infections due to carbapenem-resistant Acinetobacter baumannii. Future Pharmacol. 2023;3(2):473-87. DOI: 10.3390/futurepharmacol3020030
Vella P, Rudraraju RS, Lundbäck T, Axelsson H, Almqvist H, Vallin M, et al. A FabG inhibitor targeting an allosteric binding site inhibits several orthologs from Gram-negative ESKAPE pathogens. Bioorg Med Chem. 2021 Jan 15;30:115898. DOI: 10.1016/j.bmc.2020.115898
Carson L, Chau PKW, Earle MJ, Gilea MA, Gilmore BF, Gorman SP, et al. Antibiofilm activities of 1-alkyl-3-methylimidazolium chloride ionic liquids. Green Chem. 2009;11:492-97. DOI: 10.1039/B821842K
Cornellas A, Perez L, Comelles F, Ribosa I, Manresa A, Garcia MT. Self-aggregation and antimicrobial activity of imi-dazolium and pyridinium based ionic liquids in aqueous solution. J Colloid Interface Sci. 2011 Mar 1;355(1):164-71. DOI: 10.1016/j.jcis.2010.11.063
Caballero Gómez N, Abriouel H, Grande MJ, Pérez Pulido R, Gálvez A. Combined treatments of enterocin AS-48 with biocides to improve the inactivation of methicillin-sensitive and methicillin-resistant Staphylococcus aureus planktonic and sessile cells. Int J Food Microbiol. 2013 May 15;163(2-3):96-100. DOI: 10.1016/j.ijfoodmicro.2013.02.018
Semenyuta IV, Trush MM, Kovalishyn VV, Rogalsky SP, Hodyna DM, Karpov P, et al. Structure-activity relationship modeling and experimental validation of the imidazolium and pyridinium based ionic liquids as potential antibacterials of MDR Acinetobacter baumannii and Staphylococcus aureus. Int J Mol Sci. 2021 Jan 8;22(2):563. DOI: 10.3390/ijms22020563
Hafez NFM, Mutalib MIA, Bustam MAB, El-Harbawib M, Leveque JM. Ecotoxicity of pyridinium based Ils towards guppy fish and four bacterial strains. Procedia Eng. 2016;148:830-8. DOI: 10.1016/j.proeng.2016.06.625
Trush M, Metelytsia L, Semenyuta I, Kalashnikova L, Papeykin O, Venger I, et al. Reduced ecotoxicity and improved biodegradability of cationic biocides based on ester-functionalized pyridinium ionic liquids. Environ Sci Pollut Res Int. 2019 Feb;26(5):4878-89. DOI: 10.1007/s11356-018-3924-8
Hodyna D, Bardeau JF, Metelytsia L, Riabov S, Kobrina L, Laptiy S, et al. Efficient antimicrobial activity and reduced toxicity of 1-dodecyl-3-methylimidazolium tetrafluoroborate ionic liquid/β-cyclodextrin complex. Chem Eng J. 2016;284:1136-45. DOI: 10.1016/j.cej.2015.09.041
Gao Y, Zhao X, Dong B, Zheng L, Li N, Zhang S. Inclusion complexes of beta-cyclodextrin with ionic liquid surfactants. J Phys Chem B. 2006 May 4;110(17):8576-81. DOI: 10.1021/jp057478f
Stella VJ, Rajewski RA. Sulfobutylether-β-cyclodextrin. Int J Pharm. 2020 Jun 15;583:119396. DOI: 10.1016/j.ijpharm.2020.119396
Bauer A, Kirby W, Sherris J, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966;45(4):493-6. DOI: 10.1093/AJCP/45.4_TS.493
OECD Guideline for testing of chemicals. Daphnia sp. Acute Immobilisation. Test No 202. 1992. p. 9.
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009 Dec;30(16):2785-91. DOI: 10.1002/jcc.21256
ChemAxon Marvin Sketch, 5.3.735 [Internet]. Chemaxon [cited 2023 Jul 16]. Available from: https://www.chemaxon.com/
Stewart computational chemistry - mopac home page [Internet]. OpenMOPAC [cited 2023 Jul 16]. Available from: http://OpenMOPAC.net/
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010 Jan 30;31(2):455-61. DOI: 10.1002/jcc.21334
Discovery Studio Visualizer, v4.0.100.13345 [Internet]. Dassault Systèmes. 2020 [cited 2023 Jul 17]. Available from: https://discover.3ds.com/discovery-studio-visualizer-download
UCLA-Doe Lab - saves v6.0 [Internet]. [cited 2023 Jul 17]. Available from: https://saves.mbi.ucla.edu/
Passino DR, Smith S. Acute bioassays and hazard evaluation of representative contaminants detected in Great Lakes fish. Environ Toxicol. Chem. 1987;6(11):901-7. DOI: 10.1002/etc.5620061111
Qu XK, Zhu LY, Li L, Wei XL, Liu F, Sun DZ. Host-guest complexation of β-, γ-cyclodextrin with alkyl trimethyl ammonium bromides in aqueous solution. J Sol Chem. 2007;36:643-50. DOI: 10.1007/s10953-007-9132-7
Gao YA, Li ZH, Du JM, Han BX, Li GZ, Hou WG, et al. Preparation and characterization of inclusion complexes of beta-cyclodextrin with ionic liquid. Chemistry. 2005 Oct 7;11(20):5875-80. DOI: 10.1002/chem.200500120
Mohamad S, Surikumaran H, Raoov M, Marimuthu T, Chandrasekaram K, Subramaniam P. Conventional study on novel dicationic ionic liquid inclusion with β-cyclodextrin. Int J Mol Sci. 2011;12(9):6329-45. DOI: 10.3390/ijms12096329
Venkata Nancharaiah Y, Reddy GK, Lalithamanasa P, Venugopalan VP. The ionic liquid 1-alkyl-3-methylimidazolium demonstrates comparable antimicrobial and antibiofilm behavior to a cationic surfactant. Biofouling. 2012;28(10):1141-9. DOI: 10.1080/08927014.2012.736966
Sayed SRM, Ezzat AO, Yassin MT, Abdelbacki MM. Synthesis, characterization and application of novel cationic surfactants as antibacterial agents. Separations. 2023;10(2):97. DOI: 10.3390/separations10020097
Yao J, Rock CO. Bacterial fatty acid metabolism in modern antibiotic discovery. Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Nov;1862(11):1300-9. DOI: 10.1016/j.bbalip.2016.09.014
Nardello-Rataj V, Leclercq L. Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens. Beilstein J Org Chem. 2014 Nov 7;10:2603-22. DOI: 10.3762/bjoc.10.273
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