Effect of new methionine-based ionic liquid on the CDR1 and CDR2 gene expression on sensitive and resistant strains of Candida albicans
,
Abstract
Background and Objectives: Previous researchers showed the antimicrobial ability of ionic liquids (ILs) on different infective agents. ILs can dissolve organic components, especially DNA molecules. Among synthesized eight binary ILs mixtures, we have chosen ([Met-HCl] [PyS]) IL for determining the antifungal ability of IL against Candida albicans cells.
Materials and Methods: Well diffusion assay, chrome agar and Germ tube tests were used to detect the Candida samples. PCR, real-time-PCR, and flow cytometry tests were performed to determine the IL's rate of toxic ability.
Results: Well diffusion assay revealed the diameters of the growth inhibition zones were the largest in IL with methionine and Proline amino acids. Minimum inhibitory concentration (MIC) and the Minimum fungicidal concentration (MFC) tests showed that they inhibited the growth of the C. albicans at a range from 250 µg/ml for sensitivity and 400 µg/ml for resistance, MIC average of all samples were 341.62 ± 4.153 µg/ml. IL reduced the expression of CDR1 and CDR2 the genes encoded by the major protein of ABC system transporter by 2.1 (P= 0.009) and 1.2 fold (P= 0.693), revealed by PCR and real time-PCR. In the flow cytometry test, there were increasing dead cells after treating with the ([Met-HCl] [PyS]) even in the most resistant strain.
Conclusion: The novel IL was effective against the most clinical and standard C. albicans.
1. Fang Z, Zheng X, Li L, Qi J, Wu W, Lu Y. Ionic liquids: emerging antimicrobial agents. Pharm Res 2022; 39: 2391-2404.
2. Zhang Q, Cai S, Zhang W, Lan Y, Zhang X. Density, viscosity, conductivity, refractive index and interaction study of binary mixtures of the ionic liquid 1–ethyl–3–methylimidazolium acetate with methyldiethanolamine. J Mol Liq 2017; 233: 471-478.
3. Wu H-B, Zhang B, Liu S-H, Chen C-C. Flammability estimation of 1-hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide. J Loss Prev Process Ind 2020; 66: 104196.
4. Petriček S. Pyridin-2-one in complexes, cocrystals and an ionic liquid. Syntheses, structures and thermal stability. J Mol Struct 2022; 1260: 132790.
5. Mero A, Guglielmero L, D'Andrea F, Pomelli CS, Guazzelli L, Koutsoumpos S, et al. Influence of the cation partner on levulinate ionic liquids properties. J Mol Liq 2022; 354: 118850.
6. Plakia A, Koulocheris V, Louli V, Voutsas E. Vapor-liquid equilibrium of acid gases with imidazolium-based ionic liquids using the UMR-PRU model. CTTA 2022; 8: 100097.
7. Guo Y, Wang Q, Ren S, Zhang M, Peng X. Numerical investigation on the wave transformation in the ionic liquid compressor for the application in hydrogen refuelling stations. Int J Hydrogen Energy 2023; 10.1016/j.ijhydene.2022.12.335.
8. Guglielmero L, Mezzetta A, Pomelli CS, Chiappe C, Guazzelli L. Evaluation of the effect of the dicationic ionic liquid structure on the cycloaddition of CO2 to epoxides. J CO2 Util 2019; 34: 437-445.
9. Singh V, Amirchand KD, Gardas RL. Ionic liquid-nanoparticle based hybrid systems for energy conversion and energy storage applications. J Taiwan Inst Chem Eng 2022; 133: 104237.
10. Shamshina JL, Rogers RD. Are myths and preconceptions preventing us from applying ionic liquid forms of antiviral medicines to the current health crisis? Int J Mol Sci 2020; 21: 6002.
11. Santos MM, Alves C, Silva J, Florindo C, Costa A, Petrovski Ž, et al. Antimicrobial activities of highly bioavailable organic salts and ionic liquids fromfluoroquinolones. Pharmaceutics 2020; 12: 694.
12. Al Kaisy GM, Mutalib MIA, Leveque JM, Rao TVVLN. Novel low viscosity ammonium-based ionic liquids with carboxylate anions: Synthesis, characterization, and thermophysical properties. J Mol Liq 2017; 230: 565-573.
13. Tan Z-Q, Liu J-F, Pang L. Advances in analytical chemistry using the unique properties of ionic liquids. TrAC Trends Anal Chem 2012; 39: 218-227.
14. Yan J, Zhu Y, Hu G, Liang Q, Ge L, Yang K. Chiral quaternary ammonium ionic liquids derived from natural dehydroabietylamine and their potential application in chiral molecular recognition. Tetrahedron 2023; 130: 133165.
15. Costa FM, Saraiva ML, Passos ML. Ionic liquids and organic salts with antimicrobial activity as a strategy against resistant microorganisms. J Mol Liq 2022; 368: 120750.
16. Reddy GKK, Nancharaiah YV. Alkylimidazolium ionic liquids as antifungal alternatives: antibiofilm activity against Candida albicans and underlying mechanism of action. Front Microbiol 2020; 11: 730.
17. Maheronnaghsh M, Teimoori A, Dehghan P, Fatahinia M. The evaluation of the overexpression of the ERG-11, MDR-1, CDR-1, and CDR-2 genes in fluconazole-resistant Candida albicans isolated from Ahvazian cancer patients with oral candidiasis. J Clin Lab Anal 2022; 36(2): e24208.
18. Yang Y-J, Liu Y, Liu D-D, Guo W-Z, Wang L-X, Wang X-J, et al. Development of a flow cytometry-based plating-free system for strain engineering in industrial fungi. Appl Microbiol Biotechnol 2022; 106: 713-727.
19. Singh SK, Savoy AW. Ionic liquids synthesis and applications: An overview. J Mol Liq 2020; 297: 112038.
20. 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: 1141-1149.
21. Černáková L, Líšková A, Lengyelová L, Rodrigues CF. Prevalence and antifungal susceptibility profile of oral Candida spp. Isolates from a Hospital in Slovakia. Medicina (Kaunas) 2022; 58: 576.
22. Suchodolski J, Feder-Kubis J, Krasowska A. Antiadhesive properties of imidazolium ionic liquids based on (−)-Menthol against Candida spp. Int J Mol Sci 2021; 22: 7543.
23. Jampilek J. Novel avenues for identification of new antifungal drugs and current challenges. Expert Opin Drug Discov 2022; 17: 949-968.
24. Gong Y, Yin S, Sun S, Li M. Chelerythrine reverses the drug resistance of resistant Candida albicans and the biofilm to fluconazole. Future Microbiol 2022; 17: 1325-1333.
25. Agrawal D, Patterson T, Rinaldi M, Revankar S. Trailing end-point phenotype of Candida spp. in antifungal susceptibility testing to fluconazole is eliminated by altering incubation temperature. J Med Microbiol 2007; 56: 1003-1004.
26. Braga-Silva LA, Mesquita DG, Ribeiro MD, Carvalho SM, Fracalanzza SE, Santos AL. Trailing end-point phenotype antibiotic-sensitive strains of Candida albicans produce different amounts of aspartyl peptidases. Braz J Med Biol Res 2009; 42: 765-770.
27. Kaur J, Nobile CJ. Antifungal drug-resistance mechanisms in Candida biofilms. Curr Opin Microbiol 2023; 71: 102237.
28. Stevens DA, Espiritu M, Parmar R. Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. Antimicrob Agents Chemother 2004; 48: 3407-3411.
29. De Jong AW, Van Veldhuizen D, Groot AT, Hagen F. Standardized methods to rear high‐quality Galleria mellonella larvae for the study of fungal pathogens. Entomol Exp Appl 2022; 170: 1073-1080.
30. Cantón E, Pemán J, Gobernado M, Viudes A, Espinel-Ingroff A. Patterns of amphotericin B killing kinetics against seven Candida species. Antimicrob Agents Chemother 2004; 48: 2477-2482.
31. Lima A, Widen R, Vestal G, Uy D, Silbert S. A TaqMan probe-based real-time PCR assay for the rapid identification of the emerging multidrug-resistant pathogen Candida auris on the BD Max system. J Clin Microbiol 2019; 57(7): e01604-18.
32. Simões M, Pereira AR, Simões LC, Cagide F, Borges F. Biofilm control by ionic liquids. Drug Discov Today 2021; 26: 1340-1346.
33. Reddy GKK, Nancharaiah YV. Alkylimidazolium ionic liquids as antifungal alternatives: antibiofilm activity against Candida albicans and underlying mechanism of action. Front Microbiol 2020; 11: 730.
34. Schrekker CM, Sokolovicz YC, Raucci MG, Selukar BS, Klitzke JS, Lopes W, et al. Multitask imidazolium salt additives for innovative poly (l-lactide) biomaterials: morphology control, Candida spp. biofilm inhibition, human mesenchymal stem cell biocompatibility, and skin tolerance. ACS Appl Mater Interfaces 2016; 8: 21163-21176.
35. Guo H-Y, Cao B, Deng G, Hao X-L, Wu F-G, Yu Z-W. Effect of imidazolium-based ionic liquids on the structure and phase behavior of palmitoyl-oleoyl-phosphatidylethanolamine. J Phys Chem B 2019; 123: 5474-5482.
36. Takamuku T, Hoke H, Idrissi A, Marekha BA, Moreau M, Honda Y, et al. Microscopic interactions of the imidazolium-based ionic liquid with molecular liquids depending on their electron-donicity. Phys Chem Chem Phys 2014; 16: 23627-23638.
37. Kiran Kumar Reddy G, Nancharaiah YV. Alkylimidazolium ionic liquids for biofilm control: Experimental studies on controlling multispecies biofilms in natural waters. J Mol Liq 2021; 336: 116859.
38. Li Y, Yang F, Li Y, Cai M, Li H, Fan X, et al. Choline amino acid ionic liquids: A novel green potential lubricant. J Mol Liq 2022; 360: 119539.
39. Michalski J, Odrzygóźdź C, Mester P, Narożna D, Cłapa T. Defeat undefeatable: ionic liquids as novel antimicrobial agents. J Mol Liq 2023; 369: 120782.
40. Dimitrić N, Spremo N, Vraneš M, Belić S, Karaman M, Kovačević S, et al. New protic ionic liquids for fungi and bacteria removal from paper heritage artefacts. RSC Adv 2019; 9: 17905-17912.
41. Yang DD, Paterna NJ, Senetra AS, Casey KR, Trieu PD, Caputo GA, et al. Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy. iScience 2021; 24: 101853.
42. Chen LM, Xu YH, Zhou CL, Zhao J, Li CY, Wang R. Overexpression of CDR1 and CDR2 Genes plays an important role in fluconazole resistance in Candida albicans with G487T and T916C Mutations. J Int Med Res 2010; 38: 536-545.
43. Suchodolski J, Krasowska A. Fructose induces fluconazole resistance in Candida albicans through activation of Mdr1 and CDR1 transporters. Int J Mol Sci 2021; 22: 2127.
44. Borgeat V, Brandalise D, Grenouillet F, Sanglard D. Participation of the ABC Transporter CDR1 in Azole Resistance of Candida lusitaniae. J Fungi (Basel) 2021; 7: 760.
45. Shao J, Zhang M, Wang T, Li Y, Wang C. The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans. Pharm Biol 2016; 54: 984-992.
46. Valli M, Sauer M, Branduardi P, Borth N, Porro D, Mattanovich D. Intracellular pH distribution in Saccharomyces cerevisiae cell populations, analyzed by flow cytometry. Appl Environ Microbiol 2005; 71: 1515-1521.
47. Hernlem B, Hua S-S. Dual fluorochrome flow cytometric assessment of yeast viability. Curr Microbiol 2010; 61: 57-63.
48. Cook K, Tarnawsky K, Swinton AJ, Yang DD, Senetra AS, Caputo GA, et al. Correlating lipid membrane permeabilities of imidazolium ionic liquids with their cytotoxicities on yeast, bacterial, and mammalian cells. Biomolecules 2019; 9: 251.
2. Zhang Q, Cai S, Zhang W, Lan Y, Zhang X. Density, viscosity, conductivity, refractive index and interaction study of binary mixtures of the ionic liquid 1–ethyl–3–methylimidazolium acetate with methyldiethanolamine. J Mol Liq 2017; 233: 471-478.
3. Wu H-B, Zhang B, Liu S-H, Chen C-C. Flammability estimation of 1-hexyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide. J Loss Prev Process Ind 2020; 66: 104196.
4. Petriček S. Pyridin-2-one in complexes, cocrystals and an ionic liquid. Syntheses, structures and thermal stability. J Mol Struct 2022; 1260: 132790.
5. Mero A, Guglielmero L, D'Andrea F, Pomelli CS, Guazzelli L, Koutsoumpos S, et al. Influence of the cation partner on levulinate ionic liquids properties. J Mol Liq 2022; 354: 118850.
6. Plakia A, Koulocheris V, Louli V, Voutsas E. Vapor-liquid equilibrium of acid gases with imidazolium-based ionic liquids using the UMR-PRU model. CTTA 2022; 8: 100097.
7. Guo Y, Wang Q, Ren S, Zhang M, Peng X. Numerical investigation on the wave transformation in the ionic liquid compressor for the application in hydrogen refuelling stations. Int J Hydrogen Energy 2023; 10.1016/j.ijhydene.2022.12.335.
8. Guglielmero L, Mezzetta A, Pomelli CS, Chiappe C, Guazzelli L. Evaluation of the effect of the dicationic ionic liquid structure on the cycloaddition of CO2 to epoxides. J CO2 Util 2019; 34: 437-445.
9. Singh V, Amirchand KD, Gardas RL. Ionic liquid-nanoparticle based hybrid systems for energy conversion and energy storage applications. J Taiwan Inst Chem Eng 2022; 133: 104237.
10. Shamshina JL, Rogers RD. Are myths and preconceptions preventing us from applying ionic liquid forms of antiviral medicines to the current health crisis? Int J Mol Sci 2020; 21: 6002.
11. Santos MM, Alves C, Silva J, Florindo C, Costa A, Petrovski Ž, et al. Antimicrobial activities of highly bioavailable organic salts and ionic liquids fromfluoroquinolones. Pharmaceutics 2020; 12: 694.
12. Al Kaisy GM, Mutalib MIA, Leveque JM, Rao TVVLN. Novel low viscosity ammonium-based ionic liquids with carboxylate anions: Synthesis, characterization, and thermophysical properties. J Mol Liq 2017; 230: 565-573.
13. Tan Z-Q, Liu J-F, Pang L. Advances in analytical chemistry using the unique properties of ionic liquids. TrAC Trends Anal Chem 2012; 39: 218-227.
14. Yan J, Zhu Y, Hu G, Liang Q, Ge L, Yang K. Chiral quaternary ammonium ionic liquids derived from natural dehydroabietylamine and their potential application in chiral molecular recognition. Tetrahedron 2023; 130: 133165.
15. Costa FM, Saraiva ML, Passos ML. Ionic liquids and organic salts with antimicrobial activity as a strategy against resistant microorganisms. J Mol Liq 2022; 368: 120750.
16. Reddy GKK, Nancharaiah YV. Alkylimidazolium ionic liquids as antifungal alternatives: antibiofilm activity against Candida albicans and underlying mechanism of action. Front Microbiol 2020; 11: 730.
17. Maheronnaghsh M, Teimoori A, Dehghan P, Fatahinia M. The evaluation of the overexpression of the ERG-11, MDR-1, CDR-1, and CDR-2 genes in fluconazole-resistant Candida albicans isolated from Ahvazian cancer patients with oral candidiasis. J Clin Lab Anal 2022; 36(2): e24208.
18. Yang Y-J, Liu Y, Liu D-D, Guo W-Z, Wang L-X, Wang X-J, et al. Development of a flow cytometry-based plating-free system for strain engineering in industrial fungi. Appl Microbiol Biotechnol 2022; 106: 713-727.
19. Singh SK, Savoy AW. Ionic liquids synthesis and applications: An overview. J Mol Liq 2020; 297: 112038.
20. 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: 1141-1149.
21. Černáková L, Líšková A, Lengyelová L, Rodrigues CF. Prevalence and antifungal susceptibility profile of oral Candida spp. Isolates from a Hospital in Slovakia. Medicina (Kaunas) 2022; 58: 576.
22. Suchodolski J, Feder-Kubis J, Krasowska A. Antiadhesive properties of imidazolium ionic liquids based on (−)-Menthol against Candida spp. Int J Mol Sci 2021; 22: 7543.
23. Jampilek J. Novel avenues for identification of new antifungal drugs and current challenges. Expert Opin Drug Discov 2022; 17: 949-968.
24. Gong Y, Yin S, Sun S, Li M. Chelerythrine reverses the drug resistance of resistant Candida albicans and the biofilm to fluconazole. Future Microbiol 2022; 17: 1325-1333.
25. Agrawal D, Patterson T, Rinaldi M, Revankar S. Trailing end-point phenotype of Candida spp. in antifungal susceptibility testing to fluconazole is eliminated by altering incubation temperature. J Med Microbiol 2007; 56: 1003-1004.
26. Braga-Silva LA, Mesquita DG, Ribeiro MD, Carvalho SM, Fracalanzza SE, Santos AL. Trailing end-point phenotype antibiotic-sensitive strains of Candida albicans produce different amounts of aspartyl peptidases. Braz J Med Biol Res 2009; 42: 765-770.
27. Kaur J, Nobile CJ. Antifungal drug-resistance mechanisms in Candida biofilms. Curr Opin Microbiol 2023; 71: 102237.
28. Stevens DA, Espiritu M, Parmar R. Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. Antimicrob Agents Chemother 2004; 48: 3407-3411.
29. De Jong AW, Van Veldhuizen D, Groot AT, Hagen F. Standardized methods to rear high‐quality Galleria mellonella larvae for the study of fungal pathogens. Entomol Exp Appl 2022; 170: 1073-1080.
30. Cantón E, Pemán J, Gobernado M, Viudes A, Espinel-Ingroff A. Patterns of amphotericin B killing kinetics against seven Candida species. Antimicrob Agents Chemother 2004; 48: 2477-2482.
31. Lima A, Widen R, Vestal G, Uy D, Silbert S. A TaqMan probe-based real-time PCR assay for the rapid identification of the emerging multidrug-resistant pathogen Candida auris on the BD Max system. J Clin Microbiol 2019; 57(7): e01604-18.
32. Simões M, Pereira AR, Simões LC, Cagide F, Borges F. Biofilm control by ionic liquids. Drug Discov Today 2021; 26: 1340-1346.
33. Reddy GKK, Nancharaiah YV. Alkylimidazolium ionic liquids as antifungal alternatives: antibiofilm activity against Candida albicans and underlying mechanism of action. Front Microbiol 2020; 11: 730.
34. Schrekker CM, Sokolovicz YC, Raucci MG, Selukar BS, Klitzke JS, Lopes W, et al. Multitask imidazolium salt additives for innovative poly (l-lactide) biomaterials: morphology control, Candida spp. biofilm inhibition, human mesenchymal stem cell biocompatibility, and skin tolerance. ACS Appl Mater Interfaces 2016; 8: 21163-21176.
35. Guo H-Y, Cao B, Deng G, Hao X-L, Wu F-G, Yu Z-W. Effect of imidazolium-based ionic liquids on the structure and phase behavior of palmitoyl-oleoyl-phosphatidylethanolamine. J Phys Chem B 2019; 123: 5474-5482.
36. Takamuku T, Hoke H, Idrissi A, Marekha BA, Moreau M, Honda Y, et al. Microscopic interactions of the imidazolium-based ionic liquid with molecular liquids depending on their electron-donicity. Phys Chem Chem Phys 2014; 16: 23627-23638.
37. Kiran Kumar Reddy G, Nancharaiah YV. Alkylimidazolium ionic liquids for biofilm control: Experimental studies on controlling multispecies biofilms in natural waters. J Mol Liq 2021; 336: 116859.
38. Li Y, Yang F, Li Y, Cai M, Li H, Fan X, et al. Choline amino acid ionic liquids: A novel green potential lubricant. J Mol Liq 2022; 360: 119539.
39. Michalski J, Odrzygóźdź C, Mester P, Narożna D, Cłapa T. Defeat undefeatable: ionic liquids as novel antimicrobial agents. J Mol Liq 2023; 369: 120782.
40. Dimitrić N, Spremo N, Vraneš M, Belić S, Karaman M, Kovačević S, et al. New protic ionic liquids for fungi and bacteria removal from paper heritage artefacts. RSC Adv 2019; 9: 17905-17912.
41. Yang DD, Paterna NJ, Senetra AS, Casey KR, Trieu PD, Caputo GA, et al. Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy. iScience 2021; 24: 101853.
42. Chen LM, Xu YH, Zhou CL, Zhao J, Li CY, Wang R. Overexpression of CDR1 and CDR2 Genes plays an important role in fluconazole resistance in Candida albicans with G487T and T916C Mutations. J Int Med Res 2010; 38: 536-545.
43. Suchodolski J, Krasowska A. Fructose induces fluconazole resistance in Candida albicans through activation of Mdr1 and CDR1 transporters. Int J Mol Sci 2021; 22: 2127.
44. Borgeat V, Brandalise D, Grenouillet F, Sanglard D. Participation of the ABC Transporter CDR1 in Azole Resistance of Candida lusitaniae. J Fungi (Basel) 2021; 7: 760.
45. Shao J, Zhang M, Wang T, Li Y, Wang C. The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans. Pharm Biol 2016; 54: 984-992.
46. Valli M, Sauer M, Branduardi P, Borth N, Porro D, Mattanovich D. Intracellular pH distribution in Saccharomyces cerevisiae cell populations, analyzed by flow cytometry. Appl Environ Microbiol 2005; 71: 1515-1521.
47. Hernlem B, Hua S-S. Dual fluorochrome flow cytometric assessment of yeast viability. Curr Microbiol 2010; 61: 57-63.
48. Cook K, Tarnawsky K, Swinton AJ, Yang DD, Senetra AS, Caputo GA, et al. Correlating lipid membrane permeabilities of imidazolium ionic liquids with their cytotoxicities on yeast, bacterial, and mammalian cells. Biomolecules 2019; 9: 251.
| Files | ||
| Issue | Vol 15 No 2 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v15i2.12485 | |
| Keywords | ||
| Ionic liquid; Candida albicans; Candidiasis; Antifungal agents; Methionine | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Eslami M, Ezabadi A, Bayat M, Omidi B, Mortazavi P. Effect of new methionine-based ionic liquid on the CDR1 and CDR2 gene expression on sensitive and resistant strains of Candida albicans. Iran J Microbiol. 2023;15(2):325-335.
