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Improving the antimicrobial efficacy against resistant Staphylococcus aureus by a combined use of conjugated oligoelectrolytes


Autoři: Elias L. Bazan aff001;  Lin Ruan aff001;  Cheng Zhou aff001
Působiště autorů: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore aff001;  Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0224816

Souhrn

Two membrane-intercalating conjugated oligoelectrolytes (COEs), namely COE-D8 and COE-S6, were combined to achieve enhanced antimicrobial efficacy. COE-D8 has a shorter molecular length than COE-S6 and is typical of effective antimicrobial COE molecules, presumably due to its prominent membrane disrupting function. In contrast, COE-D6 exhibits lower efficacy against bacteria and lower toxicity toward mammalian cells. Surprisingly, after supplementing 8 μM COE-S6, the minimum inhibitory concentration (MIC) of COE-D8 against methicillin-resistant Staphylococcus aureus (MRSA) was improved 8-fold, from 0.5 μM to 0.063 μM (0.050 μg mL−1). No increased toxicity toward mammalian cells was observed by the combination of COEs, as indicated by cytotoxicity measurements using the 3T3 cell line. Indeed, there is an extended ratio between the half maximal inhibitory concentration based on 3T3 cells to MIC against MRSA from 12 to greater than 256. Biophysical experiments using liposome models suggest that COE-S6 promotes the interactions between COE-D8 and lipid bilayers, which is in agreement with damages of cellular permeability and morphology, as observed by confocal microscopy and scanning electron microscopy. The application of a combined mixture of COEs further demonstrates their promising potential as a new class of antimicrobial agents with high efficacy and selectivity.

Klíčová slova:

Staphylococcus aureus – Methicillin-resistant Staphylococcus aureus – Antimicrobials – Cytotoxicity – Vancomycin – Scanning electron microscopy – Lipid bilayer – NIH 3T3 cells


Zdroje

1. Nikaido H. Multidrug Resistance in Bacteria. Annu Rev Biochem. 2009; 78(1):119–46. doi: 10.1146/annurev.biochem.78.082907.145923 19231985

2. Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2014; 13:42. doi: 10.1038/nrmicro3380 25435309

3. Hofer U. The cost of antimicrobial resistance. Nat Rev Microbiol. 2019; 17(1):3–. doi: 10.1038/s41579-018-0125-x 30467331

4. Falagas ME, Karageorgopoulos DE, Leptidis J, Korbila IP. MRSA in Africa: Filling the Global Map of Antimicrobial Resistance. PLoS One. 2013; 8(7):e68024. doi: 10.1371/journal.pone.0068024 23922652

5. Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci. 2002; 99(11):7687–92. doi: 10.1073/pnas.122108599 12032344

6. Turner NA, Sharma-Kuinkel BK, Maskarinec SA, Eichenberger EM, Shah PP, Carugati M, et al. Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nat Rev Microbiol. 2019; 17(4):203–18. doi: 10.1038/s41579-018-0147-4 30737488

7. LANDY M, LARKUM NW, OSWALD EJ, STREIGHTOFF F. INCREASED SYNTHESIS OF p-AMINOBENZOIC ACID ASSOCIATED WITH THE DEVELOPMENT OF SULFONAMIDE RESISTANCE IN STAPHYLOCOCCUS AUREUS. Science. 1943; 97(2516):265–7. doi: 10.1126/science.97.2516.265 17744237

8. Oakberg EF, Luria SE. Mutations to Sulfonamide Resistance in STAPHYLOCOCCUS AUREUS. Genetics. 1947; 32(3):249–61. 17247242

9. Enright MC. The evolution of a resistant pathogen–the case of MRSA. Curr Opin Pharmacol. 2003; 3(5):474–9. doi: 10.1016/s1471-4892(03)00109-7 14559091

10. Ito T, Kuwahara K, Hiramatsu K. Staphylococcal Cassette Chromosome mec (SCCmec) Analysis of MRSA. Methods Mol Biol. 2007; 391:87–102. doi: 10.1007/978-1-59745-468-1_7 18025671

11. Lee AS, de Lencastre H, Garau J, Kluytmans J, Malhotra-Kumar S, Peschel A, et al. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers. 2018; 4:18033. doi: 10.1038/nrdp.2018.33 29849094

12. Stryjewski ME, Corey GR. Methicillin-Resistant Staphylococcus aureus: An Evolving Pathogen. Clin Infect Dis. 2014; 58(suppl_1):S10–S9. doi: 10.1093/cid/cit613 24343827

13. Foster TJ. Antibiotic resistance in Staphylococcus aureus. Current status and future prospects. FEMS Microbiol Rev. 2017; 41(3):430–49. doi: 10.1093/femsre/fux007 28419231

14. Chang JY, Kim S-E, Kim TH, Woo S-Y, Ryu MS, Joo Y-H, et al. Emergence of rifampin-resistant staphylococci after rifaximin administration in cirrhotic patients. PLoS One. 2017; 12(10):e0186120. doi: 10.1371/journal.pone.0186120 28982166

15. Antonoplis A, Zang X, Huttner MA, Chong KKL, Lee YB, Co JY, et al. A Dual-Function Antibiotic-Transporter Conjugate Exhibits Superior Activity in Sterilizing MRSA Biofilms and Killing Persister Cells. J Am Chem Soc. 2018; 140(47):16140–51. doi: 10.1021/jacs.8b08711 30388366

16. Vicetti Miguel CP, Mejias A, Leber A, Sanchez PJ. A decade of antimicrobial resistance in Staphylococcus aureus: A single center experience. PLoS One. 2019; 14(2):e0212029. doi: 10.1371/journal.pone.0212029 30753206

17. Narayanaswamy VP, Giatpaiboon SA, Uhrig J, Orwin P, Wiesmann W, Baker SM, et al. In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus. PLoS One. 2018; 13(1):e0191522. doi: 10.1371/journal.pone.0191522 29342216

18. Nguyen LT, Haney EF, Vogel HJ. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol. 2011; 29(9):464–72. doi: 10.1016/j.tibtech.2011.05.001 21680034

19. Wu X, Kwon S-J, Kim J, Kane RS, Dordick JS. Biocatalytic Nanocomposites for Combating Bacterial Pathogens. Annu Rev Chem Biomol Eng. 2017; 8(1):87–113. doi: 10.1146/annurev-chembioeng-060816-101612 28592177

20. Zhang L-j Gallo RL. Antimicrobial peptides. Curr Biol. 2016; 26(1):R14–R9. doi: 10.1016/j.cub.2015.11.017 26766224

21. Siriwardena TN, Capecchi A, Gan B-H, Jin X, He R, Wei D, et al. Optimizing Antimicrobial Peptide Dendrimers in Chemical Space. Angew Chem Int Edit. 2018; 57(28):8483–7. doi: 10.1002/anie.201802837 29767453

22. Lázár V, Martins A, Spohn R, Daruka L, Grézal G, Fekete G, et al. Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides. Nat Microbl. 2018; 3(6):718–31. doi: 10.1038/s41564-018-0164-0 29795541

23. Choi H, Yang Z, Weisshaar JC. Oxidative stress induced in E. coli by the human antimicrobial peptide LL-37. PLoS Pathog. 2017; 13(6):e1006481. doi: 10.1371/journal.ppat.1006481 28665988

24. Mahlapuu M, Håkansson J, Ringstad L, Björn C. Antimicrobial Peptides: An Emerging Category of Therapeutic Agents. Front Cell Infect Microbiol. 2016; 6:194–. doi: 10.3389/fcimb.2016.00194 28083516

25. Chen CH, Starr CG, Troendle E, Wiedman G, Wimley WC, Ulmschneider JP, et al. Simulation-Guided Rational de Novo Design of a Small Pore-Forming Antimicrobial Peptide. J Am Chem Soc. 2019; 141(12):4839–48. doi: 10.1021/jacs.8b11939 30839209

26. Shen W, He P, Xiao C, Chen X. From Antimicrobial Peptides to Antimicrobial Poly(α-amino acid)s. Adv Healthc Mater. 2018; 7(20):1800354. doi: 10.1002/adhm.201800354 29923332

27. Yang Y, Cai Z, Huang Z, Tang X, Zhang X. Antimicrobial cationic polymers: from structural design to functional control. Polym J (Tokyo, Jpn). 2017; 50:33. https://doi.org/10.1038/pj.2017.72

28. Xiao F, Cao B, Wang C, Guo X, Li M, Xing D, et al. Pathogen-Specific Polymeric Antimicrobials with Significant Membrane Disruption and Enhanced Photodynamic Damage To Inhibit Highly Opportunistic Bacteria. ACS Nano. 2019; 13(2):1511–25. doi: 10.1021/acsnano.8b07251 30632740

29. Ergene C, Yasuhara K, Palermo EF. Biomimetic antimicrobial polymers: recent advances in molecular design. Polym Chem. 2018; 9(18):2407–27. https://doi.org/10.1039/C8PY00012C

30. Chin W, Zhong G, Pu Q, Yang C, Lou W, De Sessions PF, et al. A macromolecular approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset. Nat Commun. 2018; 9(1):917. doi: 10.1038/s41467-018-03325-6 29500445

31. Cuthbert TJ, Hisey B, Harrison TD, Trant JF, Gillies ER, Ragogna PJ. Surprising Antibacterial Activity and Selectivity of Hydrophilic Polyphosphoniums Featuring Sugar and Hydroxy Substituents. Angew Chem Int Edit. 2018; 57(39):12707–10. doi: 10.1002/anie.201806412 29996005

32. Li J, Zhang K, Ruan L, Chin SF, Wickramasinghe N, Liu H, et al. Block Copolymer Nanoparticles Remove Biofilms of Drug-Resistant Gram-Positive Bacteria by Nanoscale Bacterial Debridement. Nano Lett. 2018; 18(7):4180–7. doi: 10.1021/acs.nanolett.8b01000 29902011

33. Guo J, Qin J, Ren Y, Wang B, Cui H, Ding Y, et al. Antibacterial activity of cationic polymers: side-chain or main-chain type? Polym Chem. 2018; 9(37):4611–6. https://doi.org/10.1039/C8PY00665B

34. Judzewitsch PR, Nguyen T-K, Shanmugam S, Wong EHH, Boyer C. Towards Sequence-Controlled Antimicrobial Polymers: Effect of Polymer Block Order on Antimicrobial Activity. Angew Chem Int Edit. 2018; 57(17):4559–64. doi: 10.1002/anie.201713036 29441657

35. Zheng L-Y, Zhu J-F. Study on antimicrobial activity of chitosan with different molecular weights. Carbohydr Polym. 2003; 54(4):527–30. https://doi.org/10.1016/j.carbpol.2003.07.009

36. Namivandi-Zangeneh R, Kwan RJ, Nguyen T-K, Yeow J, Byrne FL, Oehlers SH, et al. The effects of polymer topology and chain length on the antimicrobial activity and hemocompatibility of amphiphilic ternary copolymers. Polym Chem. 2018; 9(13):1735–44. https://doi.org/10.1039/C7PY01069A

37. Ergene C, Palermo EF. Antimicrobial Synthetic Polymers: An Update on Structure-Activity Relationships. Curr Pharm Des. 2018; 24(8):855–65. doi: 10.2174/1381612824666180213140732 29436992

38. Wang B, Queenan BN, Wang S, Nilsson KPR, Bazan GC. Precisely Defined Conjugated Oligoelectrolytes for Biosensing and Therapeutics. Adv Mater. 2019; 31(22):1806701. doi: 10.1002/adma.201806701 30698856

39. Hinks J, Wang Y, Poh WH, Donose BC, Thomas AW, Wuertz S, et al. Modeling cell membrane perturbation by molecules designed for transmembrane electron transfer. Langmuir. 2014; 30(9):2429–40. doi: 10.1021/la403409t 24499294

40. Cheng Z, N. CGW, S. HJC, Thomas S, Talgat S, Bo L, et al. Informed Molecular Design of Conjugated Oligoelectrolytes To Increase Cell Affinity and Antimicrobial Activity. Angew Chem Int Edit. 2018; 57(27):8069–72. doi: 10.1002/anie.201803103 29707869

41. Wang B, Wang M, Mikhailovsky A, Wang S, Bazan GC. A Membrane‐Intercalating Conjugated Oligoelectrolyte with High‐Efficiency Photodynamic Antimicrobial Activity. Angew Chem Int Edit. 2017; 56(18):5031–4. doi: 10.1002/anie.201701146 28370842

42. Wang B, Feng G, Seifrid M, Wang M, Liu B, Bazan GC. Antibacterial Narrow-Band-Gap Conjugated Oligoelectrolytes with High Photothermal Conversion Efficiency. Angew Chem Int Edit. 2017; 56(50):16063–6. doi: 10.1002/anie.201709887 29073342

43. Garner LE, Park J, Dyar SM, Chworos A, Sumner JJ, Bazan GC. Modification of the optoelectronic properties of membranes via insertion of amphiphilic phenylenevinylene oligoelectrolytes. J Am Chem Soc. 2010; 132(29):10042–52. doi: 10.1021/ja1016156 20608655

44. Yan H, Rengert ZD, Thomas AW, Rehermann C, Hinks J, Bazan GC. Influence of molecular structure on the antimicrobial function of phenylenevinylene conjugated oligoelectrolytes. Chem Sci. 2016; 7(9):5714–22. doi: 10.1039/c6sc00630b 30034711

45. Zhou C, Chia GWN, Ho JCS, Moreland AS, Seviour T, Liedberg B, et al. A Chain-Elongated Oligophenylenevinylene Electrolyte Increases Microbial Membrane Stability. Adv Mater. 2019; 31(18):1808021. doi: 10.1002/adma.201808021 30908801

46. Stokes JM, MacNair CR, Ilyas B, French S, Côté J-P, Bouwman C, et al. Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance. Nat Microbl. 2017; 2:17028. doi: 10.1038/nmicrobiol.2017.28 28263303

47. Yazawa H, Zimmermann B, Asami Y, Bernimoulin J-P. Simvastatin Promotes Cell Metabolism, Proliferation, and Osteoblastic Differentiation in Human Periodontal Ligament Cells. J Periodontol. 2005; 76(2):295–302. doi: 10.1902/jop.2005.76.2.295 15974856

48. Demetzos C. Differential Scanning Calorimetry (DSC): A Tool to Study the Thermal Behavior of Lipid Bilayers and Liposomal Stability. J Liposome Res. 2008; 18(3):159–73. doi: 10.1080/08982100802310261 18770070

49. Stiefel P, Schmidt-Emrich S, Maniura-Weber K, Ren Q. Critical aspects of using bacterial cell viability assays with the fluorophores SYTO9 and propidium iodide. BMC Microbiol. 2015; 15(1):36. doi: 10.1186/s12866-015-0376-x 25881030

50. Stocks SM. Mechanism and use of the commercially available viability stain, BacLight. Cytometry A. 2004; 61A(2):189–95. doi: 10.1002/cyto.a.20069 15382024

51. Soriano A, Marco F, Martínez JA, Pisos E, Almela M, Dimova VP, et al. Influence of Vancomycin Minimum Inhibitory Concentration on the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia. Clin Infect Dis. 2008; 46(2):193–200. doi: 10.1086/524667 18171250


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