Synthesis of C-dot by hydrothermal method and evaluation of its anti-bacterial effect against antibiotic resistant S. areus and K. pneumonea

Document Type : Original Research Article


1 Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University Tehran, Iran

3 Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

4 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


Objective(s): Carbon dots (C-dots) are an emerging class of engineered nanomaterials with broad applications in medicine, bio-imaging, sensing, electronic devices, and catalysis. The study aimed to synthesize carbon nanoparticles with antibacterial therapeutic properties against clindamycin-resistant Staphylococcus aureus and ciprofloxacin-resistant Klebsiella pneumonia strains.
Methods: The C-dots were prepared by a hydrothermal method. Then the synthesized carbon dot were characterized by UV-visible spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy and transmission electron microscopy. The minimum inhibitory concentration of C-dots was evaluated by the micro-broth dilution method. Antibiotic susceptibility testing was performed using the disk diffusion method.
Results: The C-dots significantly reduced S. aureus and K. pneumoniae strains growth when compared to untreated bacteria (control; P < 0.05). Therefore, the minimum inhibitory concentration (MIC) of C-dots for clindamycin-resistant S. areus and ciprofloxacin-resistant K. pneumoniae strains were 500 and 250 µg/ml, respectively. 
The survival percentage of S. areus and K. pneumoniae decreased to 48.05% and 11.6% respectively after treatment with 250 μg/ml C-dots. However, the viability of bacteria decreased to 3.8% and 2.5% at the concentration of 500 μg/ml. 
Conclusions: The results show that by producing antibacterial drugs at the nanoscale, C-dots are a promising new approach to improve the effectiveness of treating infections caused by antibiotic-resistant bacterial strains.


Main Subjects

  1. Chung H, Merakou C, Schaefers MM, Flett KB, Martini S, Lu R, et al. Rapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections. Nat Commun. 2022;13(1).
  2. Miethke M, Pieroni M, Weber T, Brönstrup M, Hammann P, Halby L, et al. Towards the sustainable discovery and development of new antibiotics. Nat Rev Chem [Internet]. 2021;5(10):726-49. Available from:  
  3. Wang Y, Jin Y, Chen W, Wang J, Chen H, Sun L, et al. Construction of nanomaterials with targeting phototherapy properties to inhibit resistant bacteria and biofilm infections. Chem Eng J [Internet]. 2019;358:74-90. Available from:  
  4. Liang G, Shi H, Qi Y, Li J, Jing A, Liu Q, et al. Specific anti-biofilm activity of carbon quantum dots by destroying p. gingivalis biofilm related genes. Int J Nanomedicine. 2020;15:5473-89.  
  5. Jian H-J, Wu RS, Lin TY, Li YJ, Lin HJ, Harroun SG, et al. Super-Cationic Carbon Quantum Dots Synthesized from Spermidine as an Eye Drop Formulation for Topical Treatment of Bacterial Keratitis. ACS Nano. 2017;11:6703.  
  6. Li P, Liu S, Cao W, Zhang G, Yang X, Gong X, et al. Low-toxicity carbon quantum dots derived from gentamicin sulfate to combat antibiotic resistance and eradicate mature biofilms. Chem Commun. 2020;56(15):2316-9.  
  7. Li H, Huang J, Song Y, Zhang M, Wang H, Lu F, et al. Degradable Carbon Dots with Broad-Spectrum Antibacterial Activity. ACS Appl Mater Interfaces [Internet]. 2018 Aug 15;10(32):26936-46. Available from:  
  8. Song Y, Lu F, Li H, Wang H, Zhang M, Liu Y, et al. Degradable Carbon Dots from Cigarette Smoking with Broad-Spectrum Antimicrobial Activities against Drug-Resistant Bacteria. ACS Appl Bio Mater. 2018;1(6):1871-9.  
  9. Wu Y, van der Mei HC, Busscher HJ, Ren Y. Enhanced bacterial killing by vancomycin in staphylococcal biofilms disrupted by novel, DMMA-modified carbon dots depends on EPS production. Colloids Surfaces B Biointerfaces [Internet]. 2020;193(March):111114. Available from:  
  10. Lin F, Li C, Chen Z. Bacteria-derived carbon dots inhibit biofilm formation of Escherichia coli without affecting cell growth. Front Microbiol. 2018;9(FEB):1-9.  
  11. Wang H, Lu F, Ma C, Ma Y, Zhang M, Wang B, et al. Carbon dots with positive surface charge from tartaric acid and m-aminophenol for selective killing of Gram-positive bacteria. J Mater Chem B. 2021;9(1):125-30.  
  12. Duin D Van, Paterson DL. Multidrug Resistant Bacteria in the Community : An Update. 2021;34(4):709-22.  
  13. Neill JO'. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations The Review on Antimicrobial Resistance Chaired. 2014;(December).  
  14. Dresler S, Szymczak G, Wójcik M. Comparison of some secondary metabolite content in the seventeen species of the boraginaceae family. Pharm Biol. 2017;55(1):691-5.  
  15. CLSI. CLSI M100-ED29: 2021 Performance Standards for Antimicrobial Susceptibility Testing, 30th Edition. Vol. 40, Clsi. 2020. 50-51 p.  
  16. Custovic A, Smajlovic J, Hadzic S, Ahmetagic S, Tihic N, Hadzagic H. Epidemiological Surveillance of Bacterial Nosocomial Infections in the Surgical Intensive Care Unit. Mater Socio Medica. 2014;26(1):7.  
  17. Zhao D, Zhang R, Liu X, Li X, Xu M, Huang X, et al. Screening of Chitosan Derivatives-Carbon Dots Based on Antibacterial Activity and Application in Anti-Staphylococcus aureus Biofilm. Int J Nanomedicine. 2022;17(February):937-52.  
  18. Varghese M, Balachandran M. Antibacterial efficiency of carbon dots against Gram-positive and Gram-negative bacteria: A review. J Environ Chem Eng [Internet]. 2021;9(6):106821. Available from:  
  19. Li P, Poon YF, Li W, Zhu HY, Yeap SH, Cao Y, et al. A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability. Nat Mater [Internet]. 2011;10(2):149-56. Available from:  
  20. Varghese M, Balachandran M. Antibacterial efficiency of carbon dots against Gram-positive and Gram-negative bacteria: A review. J Environ Chem Eng. 2021;9(6).  
  21. Ye Z, Li G, Lei J, Liu M, Jin Y, Li B. One-Step and One-Precursor Hydrothermal Synthesis of Carbon Dots with Superior Antibacterial Activity. Vol. 3, ACS Applied Bio Materials. 2020. 7095-7102 p.  
  22. Li Y-J, Harroun SG, Su Y-C, Huang C-F, Unnikrishnan B, Lin H-J, et al. Synthesis of Self-Assembled Spermidine-Carbon Quantum Dots Effective against Multidrug-Resistant Bacteria. Adv Healthc Mater. 2016;5:2545.  
  23. Bing W, Sun H, Yan Z, Ren J, Qu X. Programmed Bacteria Death Induced by Carbon Dots with Different Surface Charge. Small. 2016;12:4713.  
  24. Su S, Shelton CB. Size Dependent Antibacterial Behavior. ASME Int Mech Eng Congr Expo Proc. 2016;15:1-4.  
  25. Wu Y, Yang G, Mei HC Van Der, Shi L, Busscher HJ. Synergy between " Probiotic " Carbon Quantum Dots and Ciprofloxacin in Eradicating Infectious Biofilms and Their Biosafety in Mice. 2021;  
  26. Bojang E, Jafali J, Perreten V, Hart J, Harding-Esch EM, Sillah A, et al. Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control. BMC Microbiol. 2017;17(1):1-10.  
  27. den Heijer CDJ, van Bijnen EME, Paget WJ, Pringle M, Goossens H, Bruggeman CA, et al. Prevalence and resistance of commensal Staphylococcus aureus, including meticillin-resistant S aureus, in nine European countries: A cross-sectional study. Lancet Infect Dis [Internet]. 2013;13(5):409-15. Available from:  
  28. Aqel AA, Ibrahim A, Shehabi A. Rare occurrence of mupirocin resistance among clinical Staphylococcus isolates in Jordan. Acta Microbiol Immunol Hung. 2012;59(2):239-47.  
  29. Desroches M, Potier J, Laurent F, Bourrel AS, Doucet-Populaire F, Decousser JW, et al. Prevalence of mupirocin resistance among invasive coagulase-negative staphylococci and methicillin-resistan Staphylococcus aureus (MRSA) in France: Emergence of a mupirocin-resistant MRSA clone harbouring mupA. J Antimicrob Chemother. 2013;68(8):1714-7.  
  30. Petinaki E, Spiliopoulou I, Kontos F, Maniati M, Bersos Z, Stakias N, et al. Clonal dissemination of mupirocin-resistant staphylococci in Greek hospitals. J Antimicrob Chemother. 2004;53(1):105-8.  
  31. Abbasi-Montazeri E, Khosravi AD, Feizabadi MM, Goodarzi H, Khoramrooz SS, Mirzaii M, et al. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) isolates with high-level mupirocin resistance from patients and personnel in a burn center. Burns [Internet]. 2013;39(4):650-4. Available from:  
  32. Goudarzi M, Kobayashi N, Dadashi M, Pantůček R, Nasiri MJ, Fazeli M, et al. Prevalence, Genetic Diversity, and Temporary Shifts of Inducible Clindamycin Resistance Staphylococcus aureus Clones in Tehran, Iran: A Molecular-Epidemiological Analysis From 2013 to 2018. Front Microbiol. 2020;11(April):1-18.  
  33. Castanheira M, Watters AA, Bell JM, Turnidge JD, Jones RN. Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. isolated in North America and Australia, 2007-2008. Antimicrob Agents Chemother. 2010;54(9):3614-7.  
  34. Rezaie Keikhaie K, Sargazi A, Hassansnhahian M, Shahi Z. Detection of Intracellular Adhesion (ica) and Biofilm Formation Genes in Staphylococcus aureus Isolates from Clinical Samples. Res Mol Med. 2017;5(1):40-3.  
  35. Kamali E, Jamali A, Ardebili A, Ezadi F, Mohebbi A. Evaluation of antimicrobial resistance, biofilm forming potential, and the presence of biofilm-related genes among clinical isolates of Pseudomonas aeruginosa. BMC Res Notes [Internet]. 2020;13(1):4-9. Available from:  
  36. Ayatollahi J, Sharifyazdi M, Fadakarfard R, Hossein S. Antibiotic resistance pattern of Klebsiella pneumoniae in obtained samples from Ziaee Hospital of Ardakan , Yazd , Iran during 2016 to 2017. 2020;02:32-6.  
  37. Alcántar-curiel MD, Ledezma-escalante CA, Jarillo-quijada MD, Gayosso-vázquez C, Morf R, Rodr E, et al. Association of Antibiotic Resistance , Cell Adherence , and Biofilm Production with the Endemicity of Nosocomial Klebsiella pneumoniae. 2018;2018.  
  38. Ahanjan M, Naderi F, Solimanii A, Practitioner G. Prevalence of Beta-lactamases Genes and Antibiotic Resistance Pattern of Klebsiella pneumoniae Isolated from Teaching hospitals, Sari, Iran, 2014. Journal of Mazandaran University of Medical Sciences. 2017 Jun 10;27(149):79-87.  
  39. Queenan AM, Bush K. Carbapenemases : the Versatile -Lactamases. 2007;20(3):440-58.