Farnesol Emulsion as an Effective Broad-Spectrum Agent against ESKAPE Biofilms
Abstract
:1. Introduction
2. Results
2.1. Farnesol Impedes Biofilm Development
2.2. Farnesol Disrupts Established Biofilms
2.3. No Resistance to Farnesol Was Observed
2.4. Farnesol Directly Kills Bacteria and Also Detaches Biofilms
2.5. Farnesol Is Effective against Biofilm-Associated Skin Infections
3. Discussion
4. Materials and Methods
4.1. Bacterial Strains and Culture
4.2. OD600 and Determining CFU/mL
4.3. Inhibiting Biofilm Formation
4.4. Disrupting Established Biofilms
4.5. Viability Assay Using Live/Dead with Quantitative Microscopy
4.6. Evaluation of Antimicrobial Resistance
4.7. Evaluation of Cell Membrane Damage Using Propidium Iodide (PI)
4.8. Developing and Treating Biofilms on Ex Vivo Human Skin
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Mulani, M.S.; Kamble, E.E.; Kumkar, S.N.; Tawre, M.S.; Pardesi, K.R. Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review. Front. Microbiol. 2019, 10, 539. [Google Scholar] [CrossRef] [PubMed]
- Rice, L.B. Federal Funding for the Study of Antimicrobial Resistance in Nosocomial Pathogens: No ESKAPE. J. Infect. Dis. 2008, 197, 1079–1081. [Google Scholar] [CrossRef] [PubMed]
- Santajit, S.; Indrawattana, N. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. BioMed Res. Int. 2016, 2016, e2475067. [Google Scholar] [CrossRef] [PubMed]
- Tacconelli, E.; Carrara, E.; Savoldi, A.; Harbarth, S.; Mendelson, M.; Monnet, D.L.; Pulcini, C.; Kahlmeter, G.; Kluytmans, J.; Carmeli, Y.; et al. Discovery, Research, and Development of New Antibiotics: The WHO Priority List of Antibiotic-Resistant Bacteria and Tuberculosis. Lancet Infect. Dis. 2018, 18, 318–327. [Google Scholar] [CrossRef] [PubMed]
- Costerton, J.W.; Stewart, P.S.; Greenberg, E.P. Bacterial Biofilms: A Common Cause of Persistent Infections. Science 1999, 284, 1318–1322. [Google Scholar] [CrossRef] [PubMed]
- Davies, D. Understanding Biofilm Resistance to Antibacterial Agents. Nat. Rev. Drug. Discov. 2003, 2, 114–122. [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] [PubMed]
- Hall, C.W.; Mah, T.-F. Molecular Mechanisms of Biofilm-Based Antibiotic Resistance and Tolerance in Pathogenic Bacteria. FEMS Microbiol. Rev. 2017, 41, 276–301. [Google Scholar] [CrossRef] [PubMed]
- Langford, B.J.; So, M.; Raybardhan, S.; Leung, V.; Westwood, D.; MacFadden, D.R.; Soucy, J.-P.R.; Daneman, N. Bacterial Co-Infection and Secondary Infection in Patients with COVID-19: A Living Rapid Review and Meta-Analysis. Clin. Microbiol. Infect. 2020, 26, 1622–1629. [Google Scholar] [CrossRef]
- Catalano, A.; Iacopetta, D.; Ceramella, J.; Pellegrino, M.; Giuzio, F.; Marra, M.; Rosano, C.; Saturnino, C.; Sinicropi, M.S.; Aquaro, S. Antibiotic-Resistant ESKAPE Pathogens and COVID-19: The Pandemic beyond the Pandemic. Viruses 2023, 15, 1843. [Google Scholar] [CrossRef] [PubMed]
- Loyola-Cruz, M.Á.; Gonzalez-Avila, L.U.; Martínez-Trejo, A.; Saldaña-Padilla, A.; Hernández-Cortez, C.; Bello-López, J.M.; Castro-Escarpulli, G. ESKAPE and Beyond: The Burden of Coinfections in the COVID-19 Pandemic. Pathogens 2023, 12, 743. [Google Scholar] [CrossRef]
- Lugito, N.P.H.; Cucunawangsih, C.; Wiwing, V.; Suryadinata, N. Prevalence of Antimicrobial Resistance of ESKAPE Pathogens before and during Pandemic COVID-19 Pandemic in a University Affiliated Hospital in Tangerang, Indonesia. Open J. Med. Microbiol. 2023, 13, 146–158. [Google Scholar] [CrossRef]
- Ku, C.-M.; Lin, J.-Y. Farnesol, a Sesquiterpene Alcohol in Essential Oils, Ameliorates Serum Allergic Antibody Titres and Lipid Profiles in Ovalbumin-Challenged Mice. Allergol. Et Immunopathol. 2016, 44, 149–159. [Google Scholar] [CrossRef]
- de Araújo Delmondes, G.; Bezerra, D.S.; de Queiroz Dias, D.; de Souza Borges, A.; Araújo, I.M.; Lins da Cunha, G.; Bandeira, P.F.R.; Barbosa, R.; Melo Coutinho, H.D.; Felipe, C.F.B.; et al. Toxicological and Pharmacologic Effects of Farnesol (C15H26O): A Descriptive Systematic Review. Food Chem. Toxicol. 2019, 129, 169–200. [Google Scholar] [CrossRef]
- Lapczynski, A.; Bhatia, S.P.; Letizia, C.S.; Api, A.M. Fragrance Material Review on Farnesol. Food Chem. Toxicol. 2008, 46, S149–S156. [Google Scholar] [CrossRef]
- Burdock, G.A. Fenaroli’s Handbook of Flavor Ingredients, 6th ed.; CRC Press: Boca Raton, FL, USA, 2009; ISBN 978-0-429-15083-8. [Google Scholar]
- Ramage, G.; Saville, S.P.; Wickes, B.L.; López-Ribot, J.L. Inhibition of Candida Albicans Biofilm Formation by Farnesol, a Quorum-Sensing Molecule. Appl. Environ. Microbiol. 2002, 68, 5459–5463. [Google Scholar] [CrossRef]
- Fernandes, R.A.; Monteiro, D.R.; Arias, L.S.; Fernandes, G.L.; Delbem, A.C.B.; Barbosa, D.B. Biofilm Formation by Candida Albicans and Streptococcus Mutans in the Presence of Farnesol: A Quantitative Evaluation. Biofouling 2016, 32, 329–338. [Google Scholar] [CrossRef]
- Lee, J.H.; Kim, C.; Kim, S.-H.; Sethi, G.; Ahn, K.S. Farnesol Inhibits Tumor Growth and Enhances the Anticancer Effects of Bortezomib in Multiple Myeloma Xenograft Mouse Model through the Modulation of STAT3 Signaling Pathway. Cancer Lett. 2015, 360, 280–293. [Google Scholar] [CrossRef]
- Szűcs, G.; Murlasits, Z.; Török, S.; Kocsis, G.F.; Pálóczi, J.; Görbe, A.; Csont, T.; Csonka, C.; Ferdinandy, P. Cardioprotection by Farnesol: Role of the Mevalonate Pathway. Cardiovasc. Drugs Ther. 2013, 27, 269–277. [Google Scholar] [CrossRef] [PubMed]
- Vinholes, J.; Rudnitskaya, A.; Gonçalves, P.; Martel, F.; Coimbra, M.A.; Rocha, S.M. Hepatoprotection of Sesquiterpenoids: A Quantitative Structure–Activity Relationship (QSAR) Approach. Food Chem. 2014, 146, 78–84. [Google Scholar] [CrossRef] [PubMed]
- Jo, A.; Lee, Y.; Kam, T.-I.; Kang, S.-U.; Neifert, S.; Karuppagounder, S.S.; Khang, R.; Kang, H.; Park, H.; Chou, S.-C.; et al. PARIS Farnesylation Prevents Neurodegeneration in Models of Parkinson’s Disease. Sci. Transl. Med. 2021, 13, eaax8891. [Google Scholar] [CrossRef] [PubMed]
- Pammi, M.; Liang, R.; Hicks, J.M.; Barrish, J.; Versalovic, J. Farnesol Decreases Biofilms of Staphylococcus Epidermidis and Exhibits Synergy With Nafcillin and Vancomycin. Pediatr. Res. 2011, 70, 578–583. [Google Scholar] [CrossRef] [PubMed]
- Kuroda, M.; Nagasaki, S.; Ohta, T. Sesquiterpene Farnesol Inhibits Recycling of the C55 Lipid Carrier of the Murein Monomer Precursor Contributing to Increased Susceptibility to β-Lactams in Methicillin-Resistant Staphylococcus aureus. J. Antimicrob. Chemother. 2007, 59, 425–432. [Google Scholar] [CrossRef] [PubMed]
- Jabra-Rizk, M.A.; Meiller, T.F.; James, C.E.; Shirtliff, M.E. Effect of Farnesol on Staphylococcus aureus Biofilm Formation and Antimicrobial Susceptibility. Antimicrob. Agents Chemother. 2006, 50, 1463–1469. [Google Scholar] [CrossRef] [PubMed]
- Han, Y.; Zhang, Y.; Zeng, W.; Huang, Z.; Cheng, H.; Kong, J.; Xu, C.; Xu, M.; Zhou, T.; Cao, J. Synergy with Farnesol Rejuvenates Colistin Activity against Colistin-Resistant Gram-Negative Bacteria in Vitro and in Vivo. Int. J. Antimicrob. Agents 2023, 62, 106899. [Google Scholar] [CrossRef] [PubMed]
- Tan, L.; Ma, R.; Reeves, T.; Katz, A.J.; Levi, N. Repurposing Farnesol for Combating Drug-Resistant and Persistent Single and Polymicrobial Biofilms. Antibiotics 2024, 13, 350. [Google Scholar] [CrossRef] [PubMed]
- Tan, L.; Ma, R.; Katz, A.J.; Levi, N. Farnesol Repurposing for Prevention and Treatment of Acinetobacter baumannii Biofilms. Biofilm 2024, 7, 100198. [Google Scholar] [CrossRef] [PubMed]
- Jamal, M.; Andleeb, S.; Jalil, F.; Imran, M.; Nawaz, M.A.; Hussain, T.; Ali, M.; ur Rahman, S.; Das, C.R. Isolation, Characterization and Efficacy of Phage MJ2 against Biofilm Forming Multi-Drug Resistant Enterobacter cloacae. Folia Microbiol. 2019, 64, 101–111. [Google Scholar] [CrossRef] [PubMed]
- Moellering, R.C. NDM-1—A Cause for Worldwide Concern. New Engl. J. Med. 2010, 363, 2377–2379. [Google Scholar] [CrossRef] [PubMed]
- Otsu, N. A Threshold Selection Method from Gray-Level Histograms. IEEE Trans. Syst. Man Cybern. 1979, 9, 62–66. [Google Scholar] [CrossRef]
- Vorregaard, M. Biofilms. In Informatics and Mathematical Modelling; Technical University of Denmark: Kongens Lyngby, Denmark, 2008. [Google Scholar]
- Inoue, Y.; Togashi, N.; Hamashima, H. Farnesol-Induced Disruption of the Staphylococcus aureus Cytoplasmic Membrane. Biol. Pharm. Bull. 2016, 39, 653–656. [Google Scholar] [CrossRef] [PubMed]
- Cerca, N.; Gomes, F.; Bento, J.C.; França, A.; Rolo, J.; Miragaia, M.; Teixeira, P.; Oliveira, R. Farnesol Induces Cell Detachment from Established S. epidermidis Biofilms. J. Antibiot. 2013, 66, 255–258. [Google Scholar] [CrossRef]
- Norbury, W.; Herndon, D.N.; Tanksley, J.; Jeschke, M.G.; Finnerty, C.C. Infection in Burns. Surg. Infect. 2016, 17, 250–255. [Google Scholar] [CrossRef]
- Azzopardi, E.A.; Azzopardi, E.; Camilleri, L.; Villapalos, J.; Boyce, D.E.; Dziewulski, P.; Dickson, W.A.; Whitaker, I.S. Gram Negative Wound Infection in Hospitalised Adult Burn Patients-Systematic Review and Metanalysis-. PLoS ONE 2014, 9, e95042. [Google Scholar] [CrossRef]
- Nisar, S.; Kirkpatrick, L.D.; Shupp, J.W. Bacterial Virulence Factors and Their Contribution to Pathophysiology after Thermal Injury. Surg. Infect. 2021, 22, 69–76. [Google Scholar] [CrossRef] [PubMed]
- James, G.A.; Swogger, E.; Wolcott, R.; Pulcini, E.d.; Secor, P.; Sestrich, J.; Costerton, J.W.; Stewart, P.S. Biofilms in Chronic Wounds. Wound Repair Regen. 2008, 16, 37–44. [Google Scholar] [CrossRef]
- Rhoads, D.D.; Cox, S.B.; Rees, E.J.; Sun, Y.; Wolcott, R.D. Clinical Identification of Bacteria in Human Chronic Wound Infections: Culturing vs. 16S Ribosomal DNA Sequencing. BMC Infect. Dis. 2012, 12, 321. [Google Scholar] [CrossRef]
- Aloke, C.; Achilonu, I. Coping with the ESKAPE Pathogens: Evolving Strategies, Challenges and Future Prospects. Microb. Pathog. 2023, 175, 105963. [Google Scholar] [CrossRef]
- Almaaytah, A.; Farajallah, A.; Abualhaijaa, A.; Al-Balas, Q. A3, a Scorpion Venom Derived Peptide Analogue with Potent Antimicrobial and Potential Antibiofilm Activity against Clinical Isolates of Multi-Drug Resistant Gram Positive Bacteria. Molecules 2018, 23, 1603. [Google Scholar] [CrossRef]
- Panlilio, H.; Lam, A.K.; Heydarian, N.; Haight, T.; Wouters, C.L.; Moen, E.L.; Rice, C.V. Dual-Function Potentiation by PEG-BPEI Restores Activity of Carbapenems and Penicillins against Carbapenem-Resistant Enterobacteriaceae. ACS Infect. Dis. 2021, 7, 1657–1665. [Google Scholar] [CrossRef] [PubMed]
- Chmielewska, S.J.; Skłodowski, K.; Piktel, E.; Suprewicz, Ł.; Fiedoruk, K.; Daniluk, T.; Wolak, P.; Savage, P.B.; Bucki, R. NDM-1 Carbapenemase-Producing Enterobacteriaceae Are Highly Susceptible to Ceragenins CSA-13, CSA-44, and CSA-131. Infect. Drug Resist. 2020, 13, 3277–3294. [Google Scholar] [CrossRef] [PubMed]
- Herigstad, B.; Hamilton, M.; Heersink, J. How to Optimize the Drop Plate Method for Enumerating Bacteria. J. Microbiol. Methods 2001, 44, 121–129. [Google Scholar] [CrossRef] [PubMed]
- Heydorn, A.; Nielsen, A.T.; Hentzer, M.; Sternberg, C.; Givskov, M.; Ersbøll, B.K.; Molin, S. Quantification of Biofilm Structures by the Novel Computer Program Comstat. Microbiology 2000, 146, 2395–2407. [Google Scholar] [CrossRef]
- de Breij, A.; Riool, M.; Cordfunke, R.A.; Malanovic, N.; de Boer, L.; Koning, R.I.; Ravensbergen, E.; Franken, M.; van der Heijde, T.; Boekema, B.K.; et al. The Antimicrobial Peptide SAAP-148 Combats Drug-Resistant Bacteria and Biofilms. Sci. Transl. Med. 2018, 10, eaan4044. [Google Scholar] [CrossRef] [PubMed]
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Tan, L.; Ma, R.; Katz, A.J.; Levi, N. Farnesol Emulsion as an Effective Broad-Spectrum Agent against ESKAPE Biofilms. Antibiotics 2024, 13, 778. https://doi.org/10.3390/antibiotics13080778
Tan L, Ma R, Katz AJ, Levi N. Farnesol Emulsion as an Effective Broad-Spectrum Agent against ESKAPE Biofilms. Antibiotics. 2024; 13(8):778. https://doi.org/10.3390/antibiotics13080778
Chicago/Turabian StyleTan, Li, Rong Ma, Adam J. Katz, and Nicole Levi. 2024. "Farnesol Emulsion as an Effective Broad-Spectrum Agent against ESKAPE Biofilms" Antibiotics 13, no. 8: 778. https://doi.org/10.3390/antibiotics13080778