Synthesized Bis-Triphenyl Phosphonium-Based Nano Vesicles Have Potent and Selective Antibacterial Effects on Several Clinically Relevant Superbugs
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Instruments
2.2. Synthesis of 1,1-(1,12-Dodecanediyl)bis[1,1,1]-triphenylphosphonium di-Bromide (BPPB)
2.3. UV-Vis Analyses
2.4. Potentiometric Titration of BPPB
Preparation of 0.1 M Perchloric Acid Volumetric Solution
2.5. Optical Microscopy Analyses
2.6. Dynamic Light Scattering (DLS) Analysis
2.7. Microbiology
2.7.1. Microorganisms
2.7.2. Determination of the MICs
2.7.3. Killing Curves
2.8. Concentration-Dependent Cytotoxicity Experiments: MTT and LHD Tests
2.8.1. MTT Cytotoxicity Assay
2.8.2. LDH Cytotoxicity Assay
2.8.3. Statistics
3. Results and Discussion
3.1. Synthesis of 1,1-(1,12-Dodecanediyl)bis[1,1,1]-triphenylphosphonium di-Bromide (BPPB)
3.2. UV-Vis Analyses
3.3. Potentiometric Titration of BPPB in Non-Aqueous Medium
3.4. Optical Microscopy Results
3.5. Particle Size, ζ-p, and PDI of BPPB
3.6. Antibacterial Properties
3.6.1. In Vitro Antibacterial Activity of BPPB: Determination of MIC Values (MICs)
An Overview of Previous Achievements by Using Antibacterial Phosphonium Salts
3.6.2. Time-Killing Curves
3.7. Cytotoxicity Experiments on Eukaryotic Cells
3.7.1. Assessment of the BPPB Concentration-Dependent Effects on Cos-7 and HepG2 Cells by MTT and LDH Essays
3.7.2. IC50 and Selectivity Indices
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ermolaev, V.V.; Arkhipova, D.M.; Miluykov, V.A.; Lyubina, A.P.; Amerhanova, S.K.; Kulik, N.V.; Voloshina, A.D.; Ananikov, V.P. Sterically Hindered Quaternary Phosphonium Salts (QPSs): Antimicrobial Activity and Hemolytic and Cytotoxic Properties. Int. J. Mol. Sci. 2021, 23, 86. [Google Scholar] [CrossRef] [PubMed]
- Saliba, R.; Zahar, J.-R.; Dabar, G.; Riachy, M.; Karam-Sarkis, D.; Husni, R. Limiting the Spread of Multidrug-Resistant Bacteria in Low-to-Middle-Income Countries: One Size Does Not Fit All. Pathogens 2023, 12, 144. [Google Scholar] [CrossRef] [PubMed]
- Dryden, M. Reactive Oxygen Species: A Novel Antimicrobial. Int. J. Antimicrob. Agents 2018, 51, 299–303. [Google Scholar] [CrossRef] [PubMed]
- Davis, S.C.; Martinez, L.; Kirsner, R. The Diabetic Foot: The Importance of Biofilms and Wound Bed Preparation. Curr. Diab Rep. 2006, 6, 439–445. [Google Scholar] [CrossRef] [PubMed]
- Alfei, S.; Caviglia, D. Prevention and Eradication of Biofilm by Dendrimers: A Possibility Still Little Explored. Pharmaceutics 2022, 14, 2016. [Google Scholar] [CrossRef] [PubMed]
- Ye, J.; Chen, X. Current Promising Strategies against Antibiotic-Resistant Bacterial Infections. Antibiotics 2022, 12, 67. [Google Scholar] [CrossRef] [PubMed]
- Balestri, A.; Cardellini, J.; Berti, D. Gold and Silver Nanoparticles as Tools to Combat Multidrug-Resistant Pathogens. Curr. Opin. Colloid. Interface Sci. 2023, 66, 101710. [Google Scholar] [CrossRef]
- Richter, S.G.; Elli, D.; Kim, H.K.; Hendrickx, A.P.A.; Sorg, J.A.; Schneewind, O.; Missiakas, D. Small Molecule Inhibitor of Lipoteichoic Acid Synthesis Is an Antibiotic for Gram-Positive Bacteria. Proc. Natl. Acad. Sci. USA 2013, 110, 3531–3536. [Google Scholar] [CrossRef]
- Alfei, S.; Schito, G.C.; Schito, A.M.; Zuccari, G. Reactive Oxygen Species (ROS)-Mediated Antibacterial Oxidative Therapies: Available Methods to Generate ROS and a Novel Option Proposal. Int. J. Mol. Sci. 2024, 25, 7182. [Google Scholar] [CrossRef] [PubMed]
- Dryden, M. Reactive Oxygen Therapy: A Novel Therapy in Soft Tissue Infection. Curr. Opin. Infect. Dis. 2017, 30, 143–149. [Google Scholar] [CrossRef]
- Dryden, M.S.; Cooke, J.; Salib, R.J.; Holding, R.E.; Biggs, T.; Salamat, A.A.; Allan, R.N.; Newby, R.S.; Halstead, F.; Oppenheim, B.; et al. Reactive Oxygen: A Novel Antimicrobial Mechanism for Targeting Biofilm-Associated Infection. J. Glob. Antimicrob. Resist. 2017, 8, 186–191. [Google Scholar] [CrossRef] [PubMed]
- Dunnill, C.; Patton, T.; Brennan, J.; Barrett, J.; Dryden, M.; Cooke, J.; Leaper, D.; Georgopoulos, N.T. Reactive Oxygen Species (ROS) and Wound Healing: The Functional Role of ROS and Emerging ROS-modulating Technologies for Augmentation of the Healing Process. Int. Wound J. 2017, 14, 89–96. [Google Scholar] [CrossRef] [PubMed]
- Bacchetti, F.; Schito, A.M.; Milanese, M.; Castellaro, S.; Alfei, S. Anti Gram-Positive Bacteria Activity of Synthetic Quaternary Ammonium Lipid and Its Precursor Phosphonium Salt. Int. J. Mol. Sci. 2024, 25, 2761. [Google Scholar] [CrossRef] [PubMed]
- Lei, Y.; Zhou, S.; Dong, C.; Zhang, A.; Lin, Y. PDMS Tri-Block Copolymers Bearing Quaternary Ammonium Salts for Epidermal Antimicrobial Agents: Synthesis, Surface Adsorption and Non-Skin-Penetration. React. Funct. Polym. 2018, 124, 20–28. [Google Scholar] [CrossRef]
- Jiao, Y.; Niu, L.; Ma, S.; Li, J.; Tay, F.R.; Chen, J. Quaternary Ammonium-Based Biomedical Materials: State-of-the-Art, Toxicological Aspects and Antimicrobial Resistance. Prog. Polym. Sci. 2017, 71, 53–90. [Google Scholar] [CrossRef]
- Zhou, C.; Wang, Y. Structure–Activity Relationship of Cationic Surfactants as Antimicrobial Agents. Curr. Opin. Colloid. Interface Sci. 2020, 45, 28–43. [Google Scholar] [CrossRef]
- Costa, S.P.F.; Azevedo, A.M.O.; Pinto, P.C.A.G.; Saraiva, M.L.M.F.S. Environmental Impact of Ionic Liquids: Recent Advances in (Eco)Toxicology and (Bio)Degradability. ChemSusChem 2017, 10, 2321–2347. [Google Scholar] [CrossRef]
- Alfei, S.; Piatti, G.; Caviglia, D.; Schito, A. Synthesis, Characterization, and Bactericidal Activity of a 4-Ammoniumbuthylstyrene-Based Random Copolymer. Polymers 2021, 13, 1140. [Google Scholar] [CrossRef]
- Zhou, Z.; Zhou, S.; Zhang, X.; Zeng, S.; Xu, Y.; Nie, W.; Zhou, Y.; Xu, T.; Chen, P. Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications. Bioconjug. Chem. 2023, 34, 302–325. [Google Scholar] [CrossRef]
- Schito, A.M.; Piatti, G.; Caviglia, D.; Zuccari, G.; Alfei, S. Broad-Spectrum Bactericidal Activity of a Synthetic Random Copolymer Based on 2-Methoxy-6-(4-Vinylbenzyloxy)-Benzylammonium Hydrochloride. Int. J. Mol. Sci. 2021, 22, 5021. [Google Scholar] [CrossRef]
- Alfei, S. Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms. Pharmaceutics 2024, 16, 80. [Google Scholar] [CrossRef] [PubMed]
- De Oliveira, D.M.P.; Forde, B.M.; Kidd, T.J.; Harris, P.N.A.; Schembri, M.A.; Beatson, S.A.; Paterson, D.L.; Walker, M.J. Antimicrobial Resistance in ESKAPE Pathogens. Clin. Microbiol. Rev. 2020, 33, e00181-19. [Google Scholar] [CrossRef]
- Zhang, C.; Cui, F.; Zeng, G.; Jiang, M.; Yang, Z.; Yu, Z.; Zhu, M.; Shen, L. Quaternary Ammonium Compounds (QACs): A Review on Occurrence, Fate and Toxicity in the Environment. Sci. Total Environ. 2015, 518–519, 352–362. [Google Scholar] [CrossRef]
- Telesiński, A.; Pawłowska, B.; Biczak, R.; Śnieg, M.; Wróbel, J.; Dunikowska, D.; Meller, E. Enzymatic Activity and Its Relationship with Organic Matter Characterization and Ecotoxicity to Aliivibrio Fischeri of Soil Samples Exposed to Tetrabutylphosphonium Bromide. Sensors 2021, 21, 1565. [Google Scholar] [CrossRef]
- Kimmig, J.; Jerchel, D. Die Wirkung von Invertseifen Auf Die Durch Pilze Und Kokken Bedingten Hautkrankheiten. Klin. Wochenschr. 1950, 28, 429–431. [Google Scholar] [CrossRef] [PubMed]
- Kanazawa, A.; Ikeda, T.; Endo, T. Synthesis and Antimicrobial Activity of Dimethyl- and Trimethyl-Substituted Phosphonium Salts with Alkyl Chains of Various Lengths. Antimicrob. Agents Chemother. 1994, 38, 945–952. [Google Scholar] [CrossRef] [PubMed]
- Alfei, S.; Schito, A.M. Positively Charged Polymers as Promising Devices against Multidrug Resistant Gram-Negative Bacteria: A Review. Polymers 2020, 12, 1195. [Google Scholar] [CrossRef] [PubMed]
- Bachowska, B.; Kazmierczak-Baranska, J.; Cieslak, M.; Nawrot, B.; Szczęsna, D.; Skalik, J.; Bałczewski, P. High Cytotoxic Activity of Phosphonium Salts and Their Complementary Selectivity towards HeLa and K562 Cancer Cells: Identification of Tri-n-butyl-n-hexadecylphosphonium Bromide as a Highly Potent Anti-HeLa Phosphonium Salt. ChemistryOpen 2012, 1, 33–38. [Google Scholar] [CrossRef] [PubMed]
- Alfei, S. Cationic Materials for Gene Therapy: A Look Back to the Birth and Development of 2,2-Bis-(Hydroxymethyl)Propanoic Acid-Based Dendrimer Scaffolds. Int. J. Mol. Sci. 2023, 24, 16006. [Google Scholar] [CrossRef]
- Pugachev, M.V.; Shtyrlin, N.V.; Sysoeva, L.P.; Nikitina, E.V.; Abdullin, T.I.; Iksanova, A.G.; Ilaeva, A.A.; Musin, R.Z.; Berdnikov, E.A.; Shtyrlin, Y.G. Synthesis and Antibacterial Activity of Novel Phosphonium Salts on the Basis of Pyridoxine. Bioorg. Med. Chem. 2013, 21, 4388–4395. [Google Scholar] [CrossRef]
- Cieniecka-Rosłonkiewicz, A.; Pernak, J.; Kubis-Feder, J.; Ramani, A.; Robertson, A.J.; Seddon, K.R. Synthesis, Anti-Microbial Activities and Anti-Electrostatic Properties of Phosphonium-Based Ionic Liquids. Green Chem. 2005, 7, 855. [Google Scholar] [CrossRef]
- Yuan, B.; Hu, W.; Lv, S.; Huang, J.; Huang, K. Synthesis of Aliphatic Symmetric Diphosphonium Salts and Bactericidal Activity of Selected Products. Chem. J. Mold. 2017, 12, 81–86. [Google Scholar] [CrossRef]
- Wei, W.; Yuan, B.; Lv, S.; Liao, Q.; Huang, J. Synthesis, Characterization and Performance of a New Type of Alkylene Triphenyl Double Quaternary Phosphonium Salt. J. Mater. Sci. Chem. Eng. 2013, 01, 61–65. [Google Scholar] [CrossRef]
- Pugachev, M.V.; Shtyrlin, N.V.; Sapozhnikov, S.V.; Sysoeva, L.P.; Iksanova, A.G.; Nikitina, E.V.; Musin, R.Z.; Lodochnikova, O.A.; Berdnikov, E.A.; Shtyrlin, Y.G. Bis-Phosphonium Salts of Pyridoxine: The Relationship between Structure and Antibacterial Activity. Bioorg. Med. Chem. 2013, 21, 7330–7342. [Google Scholar] [CrossRef]
- Lei, Q.; Lai, X.; Zhang, Y.; Li, Z.; Li, R.; Zhang, W.; Ao, N.; Zhang, H. PEGylated Bis-Quaternary Triphenyl-Phosphonium Tosylate Allows for Balanced Antibacterial Activity and Cytotoxicity. ACS Appl. Bio Mater. 2020, 3, 6400–6407. [Google Scholar] [CrossRef]
- Ceccacci, F.; Sennato, S.; Rossi, E.; Proroga, R.; Sarti, S.; Diociaiuti, M.; Casciardi, S.; Mussi, V.; Ciogli, A.; Bordi, F.; et al. Aggregation Behaviour of Triphenylphosphonium Bolaamphiphiles. J. Colloid. Interface Sci. 2018, 531, 451–462. [Google Scholar] [CrossRef] [PubMed]
- Alfei, S.; Caviglia, D.; Piatti, G.; Zuccari, G.; Schito, A.M. Synthesis, Characterization and Broad-Spectrum Bactericidal Effects of Ammonium Methyl and Ammonium Ethyl Styrene-Based Nanoparticles. Nanomaterials 2022, 12, 2743. [Google Scholar] [CrossRef] [PubMed]
- Alfei, S.; Castellaro, S.; Taptue, G.B. Synthesis and NMR Characterization of Dendrimers Based on 2,2-Bis-(Hydroxymethyl)-Propanoic Acid (Bis-HMPA) Containing Peripheral Amino Acid Residues for Gene Transfection. Org. Commun. 2017, 10, 144–177. [Google Scholar] [CrossRef]
- Alfei, S.; Castellaro, S. Synthesis and Characterization of Polyester-Based Dendrimers Containing Peripheral Arginine or Mixed Amino Acids as Potential Vectors for Gene and Drug Delivery. Macromol. Res. 2017, 25, 1172–1186. [Google Scholar] [CrossRef]
- Alfei, S.; Taptue, G.B.; Catena, S.; Bisio, A. Synthesis of Water-Soluble, Polyester-Based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids. Chin. J. Polym. Sci. 2018, 36, 999–1010. [Google Scholar] [CrossRef]
- Pifer, C.W.; Wollish, E.G. Potentiometric Titration of Salts of Organic Bases in Acetic Acid. Anal. Chem. 1952, 24, 300–306. [Google Scholar] [CrossRef]
- EUCAST. European Committee on Antimicrobial Susceptibility Testing. Available online: https://www.eucast.org/mic_and_zone_distributions_and_ecoffs (accessed on 12 August 2024).
- Schito, A.M.; Piatti, G.; Stauder, M.; Bisio, A.; Giacomelli, E.; Romussi, G.; Pruzzo, C. Effects of Demethylfruticuline A and Fruticuline A from Salvia Corrugata Vahl. on Biofilm Production in Vitro by Multiresistant Strains of Staphylococcus Aureus, Staphylococcus Epidermidis and Enterococcus Faecalis. Int. J. Antimicrob. Agents 2011, 37, 129–134. [Google Scholar] [CrossRef]
- Berridge, M.V.; Herst, P.M.; Tan, A.S. Tetrazolium Dyes as Tools in Cell Biology: New Insights into Their Cellular Reduction. Biotechnol. Annu. Rev. 2005, 11, 127–152. [Google Scholar] [PubMed]
- Kumar, P.; Nagarajan, A.; Uchil, P.D. Analysis of Cell Viability by the Lactate Dehydrogenase Assay. Cold Spring Harb. Protoc. 2018, 2018, pdb.prot095497. [Google Scholar] [CrossRef] [PubMed]
- Avalos, F.; Ortiz, J.; Zitzumbo, R.; Lopezmanchado, M.; Verdejo, R.; Arroyo, M. Phosphonium Salt Intercalated Montmorillonites. Appl. Clay Sci. 2009, 43, 27–32. [Google Scholar] [CrossRef]
- Daasch, L.; Smith, D. Infrared Spectra of Phosphorus Compounds. Anal. Chem. 1951, 23, 853–868. [Google Scholar] [CrossRef]
- Arkhipova, D.M.; Samigullina, A.I.; Minyaev, M.E.; Lyubina, A.P.; Voloshina, A.D.; Ermolaev, V.V. Synthesis, Crystal Structure, and Biological Activity of Menthol-Based Chiral Quaternary Phosphonium Salts (CQPSs). Struct. Chem. 2024, 35, 75–88. [Google Scholar] [CrossRef]
- Galkina, I.V.; Andriyashin, V.V.; Romanov, S.R.; Egorova, S.N.; Vorob’eva, N.V.; Shulaeva, M.P.; Pozdeev, O.K.; Litvinov, I.A.; Bakhtiyarova, Y.V. Synthesis, Structure and Antimicrobial Activity of Sterically Hindered Bis-Phosphonium Derivatives of 2,6-Di-Tert-Butyl-4-Methylphenol. Mendeleev Commun. 2023, 33, 635–637. [Google Scholar] [CrossRef]
- Akshay Ravindra, P.; Karpagam, S. Synthesis and Biological Activity of Azine Heterocycle Functionalized Quaternary Phosphonium Salts. IOP Conf. Ser. Mater. Sci. Eng. 2017, 263, 022017. [Google Scholar] [CrossRef]
- Kratochvil, B. Titrations in Nonaqueous Solvents. Anal. Chem. 1982, 54, 105–121. [Google Scholar] [CrossRef]
- Seher, A. Dr. I. Gyenes, C. Sc. (Chim.), Titrationen in Nichtwäßrigen Medien, 3. Neubearb. u. Erg. Aufl., 701 S., 206 Abb., 108 Tab., Gln., Ferdinand Enke Verlag, Stuttgart 1970, Preis: 84.—DM. Fette Seifen Anstrichm. 1973, 75, 232. [Google Scholar] [CrossRef]
- Šafařík, L.; Stránský, Z.; Svehla, G.; Burns, D.T. Titrimetric Analysis in Organic Solvents (Comprehensive Analytical Chemistry, Vol. XXII). Anal. Chim. Acta 1987, 201, 367. [Google Scholar] [CrossRef]
- Mascellani, G.; Casalini, C. Use of Mercuric Acetate in Potentiometric Titrations in a Nonaqueous Medium. Anal. Chem. 1975, 47, 2468–2470. [Google Scholar] [CrossRef]
- Kan, P.L.; Papahadjopoulos-Sternberg, B.; Wong, D.; Waigh, R.D.; Watson, D.G.; Gray, A.I.; McCarthy, D.; McAllister, M.; Schätzlein, A.G.; Uchegbu, I.F. Highly Hydrophilic Fused Aggregates (Microsponges) from a C12 Spermine Bolaamphiphile. J. Phys. Chem. B 2004, 108, 8129–8135. [Google Scholar] [CrossRef]
- Franceschi, S.; Andreu, V.; de Viguerie, N.; Riviere, M.; Lattes, A.; Moisand, A. Synthesis and Aggregation Behaviour of Two-Headed Surfactants Containing the Urocanic Acid Moiety. New J. Chem. 1998, 22, 225–231. [Google Scholar] [CrossRef]
- Weissig, V.; Torchilin, V.P. Cationic Bolasomes with Delocalized Charge Centers as Mitochondria-Specific DNA Delivery Systems. Adv. Drug Deliv. Rev. 2001, 49, 127–149. [Google Scholar] [CrossRef]
- Alfei, S.; Marengo, B.; Domenicotti, C. Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells. Antioxidants 2020, 9, 50. [Google Scholar] [CrossRef]
- Alfei, S.; Zuccari, G.; Caviglia, D.; Brullo, C. Synthesis and Characterization of Pyrazole-Enriched Cationic Nanoparticles as New Promising Antibacterial Agent by Mutual Cooperation. Nanomaterials 2022, 12, 1215. [Google Scholar] [CrossRef] [PubMed]
- Alfei, S.; Brullo, C.; Caviglia, D.; Zuccari, G. Preparation and Physicochemical Characterization of Water-Soluble Pyrazole-Based Nanoparticles by Dendrimer Encapsulation of an Insoluble Bioactive Pyrazole Derivative. Nanomaterials 2021, 11, 2662. [Google Scholar] [CrossRef]
- Fröhlich, E. The Role of Surface Charge in Cellular Uptake and Cytotoxicity of Medical Nanoparticles. Int. J. Nanomed. 2012, 2012, 5577–5591. [Google Scholar] [CrossRef]
- Alfei, S.; Spallarossa, A.; Lusardi, M.; Zuccari, G. Successful Dendrimer and Liposome-Based Strategies to Solubilize an Antiproliferative Pyrazole Otherwise Not Clinically Applicable. Nanomaterials 2022, 12, 233. [Google Scholar] [CrossRef]
- Petri-Fink, A.; Chastellain, M.; Juillerat-Jeanneret, L.; Ferrari, A.; Hofmann, H. Development of Functionalized Superparamagnetic Iron Oxide Nanoparticles for Interaction with Human Cancer Cells. Biomaterials 2005, 26, 2685–2694. [Google Scholar] [CrossRef] [PubMed]
- Jambhrunkar, S.; Yu, M.; Yang, J.; Zhang, J.; Shrotri, A.; Endo-Munoz, L.; Moreau, J.; Lu, G.; Yu, C. Stepwise Pore Size Reduction of Ordered Nanoporous Silica Materials at Angstrom Precision. J. Am. Chem. Soc. 2013, 135, 8444–8447. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.; Mccrate, J.M.; Lee, J.C.-M.; Li, H. The Role of Surface Charge on the Uptake and Biocompatibility of Hydroxyapatite Nanoparticles with Osteoblast Cells. Nanotechnology 2011, 22, 105708. [Google Scholar] [CrossRef]
- Akinc, A.; Battaglia, G. Exploiting Endocytosis for Nanomedicines. Cold Spring Harb. Perspect. Biol. 2013, 5, a016980. [Google Scholar] [CrossRef]
- Mondal, A.H.; Khare, K.; Saxena, P.; Debnath, P.; Mukhopadhyay, K.; Yadav, D. A Review on Colistin Resistance: An Antibiotic of Last Resort. Microorganisms 2024, 12, 772. [Google Scholar] [CrossRef]
- Silva, J.T.; López-Medrano, F. Cefiderocol, a New Antibiotic against Multidrug-Resistant Gram-Negative Bacteria. Rev. Esp. Quimioter. 2021, 34 (Suppl. S1), 41–43. [Google Scholar] [CrossRef]
- Karakonstantis, S.; Rousaki, M.; Kritsotakis, E.I. Cefiderocol: Systematic Review of Mechanisms of Resistance, Heteroresistance and In Vivo Emergence of Resistance. Antibiotics 2022, 11, 723. [Google Scholar] [CrossRef]
- Alfei, S.; Schito, A.M. β-Lactam Antibiotics and β-Lactamase Enzymes Inhibitors, Part 2: Our Limited Resources. Pharmaceuticals 2022, 15, 476. [Google Scholar] [CrossRef] [PubMed]
- Alfei, S.; Zuccari, G. Recommendations to Synthetize Old and New β-Lactamases Inhibitors: A Review to Encourage Further Production. Pharmaceuticals 2022, 15, 384. [Google Scholar] [CrossRef]
- Schito, A.M.; Piatti, G.; Caviglia, D.; Zuccari, G.; Zorzoli, A.; Marimpietri, D.; Alfei, S. Bactericidal Activity of Non-Cytotoxic Cationic Nanoparticles against Clinically and Environmentally Relevant Pseudomonas Spp. Isolates. Pharmaceutics 2021, 13, 1411. [Google Scholar] [CrossRef] [PubMed]
- García-Solache, M.; Rice, L.B. The Enterococcus: A Model of Adaptability to Its Environment. Clin. Microbiol. Rev. 2019, 32, e00058-18. [Google Scholar] [CrossRef] [PubMed]
- Levitus, M.; Rewane, A.; Perera, T.B. Vancomycin-Resistant Enterococci; StatPearls Publishing: Treasure Island, FL, USA, 2024. [Google Scholar]
- Chiang, H.-Y.; Perencevich, E.N.; Nair, R.; Nelson, R.E.; Samore, M.; Khader, K.; Chorazy, M.L.; Herwaldt, L.A.; Blevins, A.; Ward, M.A.; et al. Incidence and Outcomes Associated With Infections Caused by Vancomycin-Resistant Enterococci in the United States: Systematic Literature Review and Meta-Analysis. Infect. Control Hosp. Epidemiol. 2017, 38, 203–215. [Google Scholar] [CrossRef] [PubMed]
- Miller, W.R.; Murray, B.E.; Rice, L.B.; Arias, C.A. Vancomycin-Resistant Enterococci. Infect. Dis. Clin. N. Am. 2016, 30, 415–439. [Google Scholar] [CrossRef]
- Fernández-Hidalgo, N.; Escolà-Vergé, L. Enterococcus Faecalis Bacteremia. J. Am. Coll. Cardiol. 2019, 74, 202–204. [Google Scholar] [CrossRef]
- Rosa, T.F.; Coelho, S.S.; Foletto, V.S.; Bottega, A.; Serafin, M.B.; Machado, C.d.S.; Franco, L.N.; Paula, B.R.; Hörner, R. Alternatives for the Treatment of Infections Caused by ESKAPE Pathogens. J. Clin. Pharm. Ther. 2020, 45, 863–873. [Google Scholar] [CrossRef] [PubMed]
- Alfei, S.; Brullo, C.; Caviglia, D.; Piatti, G.; Zorzoli, A.; Marimpietri, D.; Zuccari, G.; Schito, A.M. Pyrazole-Based Water-Soluble Dendrimer Nanoparticles as a Potential New Agent against Staphylococci. Biomedicines 2021, 10, 17. [Google Scholar] [CrossRef] [PubMed]
- Bozdogan, B. Antibacterial Susceptibility of a Vancomycin-Resistant Staphylococcus Aureus Strain Isolated at the Hershey Medical Center. J. Antimicrob. Chemother. 2003, 52, 864–868. [Google Scholar] [CrossRef] [PubMed]
- Tsiodras, S.; Gold, H.S.; Sakoulas, G.; Eliopoulos, G.M.; Wennersten, C.; Venkataraman, L.; Moellering, R.C.; Ferraro, M.J. Linezolid Resistance in a Clinical Isolate of Staphylococcus Aureus. Lancet 2001, 358, 207–208. [Google Scholar] [CrossRef]
- Liu, C.; Bayer, A.; Cosgrove, S.E.; Daum, R.S.; Fridkin, S.K.; Gorwitz, R.J.; Kaplan, S.L.; Karchmer, A.W.; Levine, D.P.; Murray, B.E.; et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. Clin. Infect. Dis. 2011, 52, e18–e55. [Google Scholar] [CrossRef]
- Nour El-Din, H.T.; Yassin, A.S.; Ragab, Y.M.; Hashem, A.M. Phenotype-Genotype Characterization and Antibiotic-Resistance Correlations Among Colonizing and Infectious Methicillin-Resistant Staphylococcus Aureus Recovered from Intensive Care Units. Infect. Drug Resist. 2021, 14, 1557–1571. [Google Scholar] [CrossRef] [PubMed]
- Breijyeh, Z.; Jubeh, B.; Karaman, R. Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It. Molecules 2020, 25, 1340. [Google Scholar] [CrossRef]
- Nunes, B.; Cagide, F.; Fernandes, C.; Borges, A.; Borges, F.; Simões, M. Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus Aureus. Int. J. Mol. Sci. 2023, 25, 504. [Google Scholar] [CrossRef] [PubMed]
- Wesevich, A.; Sutton, G.; Ruffin, F.; Park, L.P.; Fouts, D.E.; Fowler, V.G.; Thaden, J.T. Newly Named Klebsiella Aerogenes (Formerly Enterobacter Aerogenes) Is Associated with Poor Clinical Outcomes Relative to Other Enterobacter Species in Patients with Bloodstream Infection. J. Clin. Microbiol. 2020, 58, e00582-20. [Google Scholar] [CrossRef] [PubMed]
- Yahav, D.; Giske, C.G.; Grāmatniece, A.; Abodakpi, H.; Tam, V.H.; Leibovici, L. New β-Lactam–β-Lactamase Inhibitor Combinations. Clin. Microbiol. Rev. 2020, 34, e00115-20. [Google Scholar] [CrossRef] [PubMed]
- Karaiskos, I.; Galani, I.; Papoutsaki, V.; Galani, L.; Giamarellou, H. Carbapenemase Producing Klebsiella Pneumoniae: Implication on Future Therapeutic Strategies. Expert Rev. Anti Infect. Ther. 2022, 20, 53–69. [Google Scholar] [CrossRef] [PubMed]
- Rolston, K.V.I.; Safdar, A. Pseudomonas, Stenotrophomonas, Acinetobacter, and Other Nonfermentative Gram-Negative Bacteria and Medically Important Anaerobic Bacteria in Transplant Recipients. In Principles and Practice of Transplant Infectious Diseases; Springer: New York, NY, USA, 2019; pp. 461–472. [Google Scholar]
- Brooke, J.S. Advances in the Microbiology of Stenotrophomonas Maltophilia. Clin. Microbiol. Rev. 2021, 34, e00030-19. [Google Scholar] [CrossRef] [PubMed]
- Sommers, K.J.; Michaud, M.E.; Hogue, C.E.; Scharnow, A.M.; Amoo, L.E.; Petersen, A.A.; Carden, R.G.; Minbiole, K.P.C.; Wuest, W.M. Quaternary Phosphonium Compounds: An Examination of Non-Nitrogenous Cationic Amphiphiles That Evade Disinfectant Resistance. ACS Infect. Dis. 2022, 8, 387–397. [Google Scholar] [CrossRef]
- Li, L.; Zhou, H.; Gai, F.; Chi, X.; Zhao, Y.; Zhang, F.; Zhao (Kent), Z. Synthesis of Quaternary Phosphonium N-Chloramine Biocides for Antimicrobial Applications. RSC Adv. 2017, 7, 13244–13249. [Google Scholar] [CrossRef]
- Xuan, J.; Chen, S.; Ning, B.; Tolleson, W.H.; Guo, L. Development of HepG2-Derived Cells Expressing Cytochrome P450s for Assessing Metabolism-Associated Drug-Induced Liver Toxicity. Chem. Biol. Interact. 2016, 255, 63–73. [Google Scholar] [CrossRef]
- Donato, M.T.; Tolosa, L.; Gómez-Lechón, M.J. Culture and Functional Characterization of Human Hepatoma HepG2 Cells. Methods Mol. Biol. 2015, 1250, 77–93. [Google Scholar] [CrossRef]
- Tolosa, L.; Gómez-Lechón, M.J.; López, S.; Guzmán, C.; Castell, J.V.; Donato, M.T.; Jover, R. Human Upcyte Hepatocytes: Characterization of the Hepatic Phenotype and Evaluation for Acute and Long-Term Hepatotoxicity Routine Testing. Toxicol. Sci. 2016, 152, 214–229. [Google Scholar] [CrossRef] [PubMed]
- Martínez-Sena, T.; Moro, E.; Moreno-Torres, M.; Quintás, G.; Hengstler, J.; Castell, J.V. Metabolomics-Based Strategy to Assess Drug Hepatotoxicity and Uncover the Mechanisms of Hepatotoxicity Involved. Arch. Toxicol. 2023, 97, 1723–1738. [Google Scholar] [CrossRef] [PubMed]
- Arzumanian, V.A.; Kiseleva, O.I.; Poverennaya, E.V. The Curious Case of the HepG2 Cell Line: 40 Years of Expertise. Int. J. Mol. Sci. 2021, 22, 13135. [Google Scholar] [CrossRef] [PubMed]
- Cushnie, T.P.T.; Cushnie, B.; Echeverría, J.; Fowsantear, W.; Thammawat, S.; Dodgson, J.L.A.; Law, S.; Clow, S.M. Bioprospecting for Antibacterial Drugs: A Multidisciplinary Perspective on Natural Product Source Material, Bioassay Selection and Avoidable Pitfalls. Pharm. Res. 2020, 37, 125. [Google Scholar] [CrossRef] [PubMed]
Sample | Weight (mg) | * MW | * P+ (mmol) | 0.1 N HClO4 (mL) | ** P+ (mmol) | ** MW | *** Residuals | Error (%) |
---|---|---|---|---|---|---|---|---|
BPPB | 280.0 | 852.7 | 0.6567 | 6.60 | 0.6600 | 848.5 | 4.2 | 0.5 |
Measure | BPPB * NPs |
---|---|
Z-Ave (nm) | 45.28 ± 3.99 |
PDI | 0.557 ± 0.03 |
ζ-p (mV) | +18.33 ± 0.98 |
Strains | BPPB (852.7) 1 | Reference Antibiotics |
---|---|---|
MIC µg/mL | MIC µg/mL | |
E. faecalis 1 VRE | 0.50 | 256 (V); 64 (T) |
E. faecalis 79 VRE | 0.50 | 256 (V); 128 (T) |
E. faecalis 365 VRE | 0.50 | 32 (V); 0.5 (T) |
E. faecalis 425 VRE | 0.50 | 32 (V); 1 (T) |
E. faecium 152 VRE | 0.25 | 128 (V); 64 (T) |
E. faecium 182 VRE | 0.25 | 64 (V); 1 (T) |
E. faecium 364 VRE | 0.50 | 32 (V); 0.5 (T) |
E. faecium 479 VRE | 0.50 | 64 (V); 1 (T) |
S. aureus A MRSA | 0.25 | 256 (O) |
S. aureus B MRSA | 0.25 | 512 (O) |
S. aureus D MSSA | 0.25 | 1 (O) |
S. aureus F MSSA | 0.50 | 0.5 (O) |
S. aureus 17 MRSA | 0.25 | 256 (O) |
S. aureus 18 MRSA | 0.25 | 512 (O) |
S. aureus 187 MRSA | 0.50 | 256 (O) |
S. aureus 195 MRSA | 0.25 | 256 (O) |
S. epidermidis 195 MRSE | 0.25 | 256 (O) |
S. epidermidis 2 MRSE | 0.25 | 128 (O) |
S. epidermidis 22 MRSE | 0.25 | 128 (O) |
S. epidermidis 171 MRSE * | 0.25 | 256 (O) |
S. epidermidis 178 MRSE * | 0.25 | 64 (O) |
S. epidermidis 181 MRSE * | 0.50 | 256 (O) |
Strains | BPPB (852.7) 1 | Reference Antibiotics |
---|---|---|
MIC µg/mL | MIC µg/mL | |
P. aeruginosa 1 V °,* | 32 | 16 (M) |
P. aeruginosa 2 V °,* | 16 | 16 (M) |
P. aeruginosa 259 °,*,** | 32 | 4 (M) |
P. aeruginosa 265 MDR *** | 32 | 16 (M) |
A. baumannii 257 * | 8 | 16 (M) |
A. baumannii 279 * | 8 | 16 (M) |
A. baumannii 283 * | 4 | 8 (M) |
A. baumannii 236 * | 8 | 16 (M) |
A. baumannii 406 * | 8 | 8 (M) |
S. maltophylia 280 | 1 | 0.5 (TMP-SMX) |
S. maltophylia 384 R TMP-SMX | 4 | 32 (TMP-SMX) |
S. maltophylia 390 | 2 | 1 (TMP-SMX) |
S. maltophylia 39 | 2 | 0.5 (TMP-SMX) |
S. maltophylia 392 | 2 | 0.5 (TMP-SMX) |
K. pneumoniae 376 *,KPC | 16 | 32 (M) |
K. pneumoniae 377 *,KPC | 16 | 16 (M) |
K. pneumoniae 488 *,KPC | 16 | 32 (M) |
K. pneumoniae 490 *,KPC,*** | 16 | 32 (M) |
K. pneumoniae 540 *,VIM,RC | 16 | 32 (M) |
K. aerogenes 500 *,KPC | 16 | 64 (M) |
E. coli 224 S | 1 | 0.03 (M) |
E. coli 462 *,NDM | 2 | 32 (M) |
E. coli 477 *,KPC | 1 | 16 (M) |
E. coli 539 *,NDM,RC | 2 | 32 (M) |
E. coli 525 *,VIM | 16 | 32 (M) |
E. cloacae 517 *,VIM | 16 | 8 (M) |
E. cloacae 527 *,VIM | 32 | 32 (M) |
E. hormaechei 544 *,VIM,RC | 32 | 32 (M) |
Strains | BPPB (852.7) 1 | Cos-7 | HepG2 |
---|---|---|---|
MIC (µg/mL) | SI | SI | |
E. faecalis | 0.50 | 11 | 23 |
E. faecium | 0.25–0.50 | 11–22 | 23–46 |
S. aureus | 0.25 | 22 | 46 |
S. epidermidis | 0.25 | 22 | 46 |
Strains | BPPB (852.7) 1 | Cos-7 | HepG2 |
---|---|---|---|
MIC (µg/mL) | SI | SI | |
P. aeruginosa | 32 | 0.2 | 0.4 |
A. baumannii | 8 | 0.7 | 1.4 |
S. maltophylia | 2 | 2.8 | 5.6 |
K. pneumoniae | 16 | 0.4 | 0.7 |
K. aerogenes | 16 | 0.4 | 0.7 |
E. coli | 1–2 | 5.5–2.8 | 11.3–5.6 |
E. cloacae | 16–32 | 0.4–0.2 | 0.7–0.4 |
E. hormaechei | 32 | 0.2 | 0.4 |
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Alfei, S.; Zuccari, G.; Bacchetti, F.; Torazza, C.; Milanese, M.; Siciliano, C.; Athanassopoulos, C.M.; Piatti, G.; Schito, A.M. Synthesized Bis-Triphenyl Phosphonium-Based Nano Vesicles Have Potent and Selective Antibacterial Effects on Several Clinically Relevant Superbugs. Nanomaterials 2024, 14, 1351. https://doi.org/10.3390/nano14161351
Alfei S, Zuccari G, Bacchetti F, Torazza C, Milanese M, Siciliano C, Athanassopoulos CM, Piatti G, Schito AM. Synthesized Bis-Triphenyl Phosphonium-Based Nano Vesicles Have Potent and Selective Antibacterial Effects on Several Clinically Relevant Superbugs. Nanomaterials. 2024; 14(16):1351. https://doi.org/10.3390/nano14161351
Chicago/Turabian StyleAlfei, Silvana, Guendalina Zuccari, Francesca Bacchetti, Carola Torazza, Marco Milanese, Carlo Siciliano, Constantinos M. Athanassopoulos, Gabriella Piatti, and Anna Maria Schito. 2024. "Synthesized Bis-Triphenyl Phosphonium-Based Nano Vesicles Have Potent and Selective Antibacterial Effects on Several Clinically Relevant Superbugs" Nanomaterials 14, no. 16: 1351. https://doi.org/10.3390/nano14161351