Synergistic effects of Zinc oxide nanoparticles and conventional antibiotics against methicillin resistant Staphylococcus aureus

Munazza Sharif, Sarfraz Ali Tunio, Shaista Bano


Background: Methicillin resistance in Staphylococcus aureus (MRSA) is creating crises in therapeutic options for the treatment of S. aureus associated infections, worldwide. Nevertheless, Zinc oxide nanoparticles (ZnO-NPs) are providing a source of an attractive broad-spectrum antibiotic. The aim of the present study was to investigate the synergistic effects of ZnO-NPs and antibiotics against mecA positive MRSA isolates.

Methods: Antibiogram of S. aureus was determined by Kirby Baur disc diffusion assay. The minimum inhibitory concentration (MIC) of antibiotics and ZnO-NPs was determined by using the broth dilution method. The mecA gene in S. aureus was detected by PCR amplification with gene specific forward and reverse primers. The effects of subinhibitory concentration of ZnO-NPs on conventional antibiotics was determined by combined disk diffusion assay.

Results: Out of two hundred clinical specimens, twenty-eight showed the growth of S. aureus. Antibiogram of the isolates showed that S. aureus have acquired resistance to the majority of the conventional antibiotics. However, no isolate showed resistance to vancomycin. The confirmed methicillin resistant S. aureus isolates were sensitive to ZnO-NPs. The antibacterial activity of ZnO-NPs appeared in a dose and time dependent manner since higher dose produced stronger effects in two hours than the effects produced from lower dose in three hours. Furthermore, ZnO-NPs enhanced the antibacterial activity of levofloxacin significantly (p < 0.001).

Conclusions: S. aureus has acquired strong resistance to multiple antibiotics. ZnO-NPs have potential synergism with levofloxacin antibiotic against the multiple drug resistant S. aureus including MRSA.    

Keywords: Levofloxacin; Synergism; Combinational therapy; MRSA 

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Aggarwal S, Jena S, Panda S, Sharma S, Dhawan B, et al. Antibiotic Susceptibility, Virulence Pattern and Typing of Staphylococcus aureus Strains Isolated from Variety of Infections in India. Frontiers in microbiology, (2019); 10(1): 1-18.

Ito T, Katayama Y, Asada K, Mori N, Tsutsumimoto K, et al. Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus. Antimicrobial agents and chemotherapy, (2001); 45(5): 1323-1336.

Lakhundi S and Zhang K. Methicillin-resistant Staphylococcus aureus: molecular characterization, evolution, and epidemiology. Clinical microbiology reviews, (2018); 31(4): 1-103.

Afreen U, Bano S, Tunio SA, Sharif M, and Mirjatt A. Evaluation of Antibacterial Activity of Zinc Oxide Nanoparticles and Acrylamide Composite Against Multidrug-Resistant Pathogenic Bacteria. Pakistan Journal of Analytical & Environmental Chemistry, (2020); 21(1): 125-131.

He W, Liu Y, Wamer WG, and Yin J-J. Electron spin resonance spectroscopy for the study of nanomaterial-mediated generation of reactive oxygen species. Journal of food and drug analysis, (2014); 22(1): 49-63.

Kadiyala U, Turali-Emre ES, Bahng JH, Kotov NA, and VanEpps JS. Unexpected insights into antibacterial activity of zinc oxide nanoparticles against methicillin resistant Staphylococcus aureus (MRSA). Nanoscale, (2018); 10(10): 4927-4939.

Liu Y, He L, Mustapha A, Li H, Hu Z, et al. Antibacterial activities of zinc oxide nanoparticles against Escherichia coli O157: H7. Journal of Applied Microbiology, (2009); 107(4): 1193-1201.

Kistler JM, Vroome CM, Ramsey FV, and Ilyas AM. Increasing multidrug antibiotic resistance in MRSA infections of the hand: a 10-year analysis of risk factors. HAND, (2020); 15(6): 877-881.

CLSI. Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Seventh Informational Supplement M100-S27. Wayne, PA, (2017).

Murakami K, Minamide W, Wada K, Nakamura E, Teraoka H, et al. Identification of methicillin-resistant strains of staphylococci by polymerase chain reaction. Journal of clinical microbiology, (1991); 29(10): 2240-2244.

Naqvi SZH, Kiran U, Ali MI, Jamal A, Hameed A, et al. Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria. International journal of nanomedicine, (2013); 8(1): 3187-3195.

Aslam B, Wang W, Arshad MI, Khurshid M, Muzammil S, et al. Antibiotic resistance: a rundown of a global crisis. Infection and drug resistance, (2018); 11(1): 1645-1658.

Salas M, Wernecki M, Fernández L, Iglesias B, Gutiérrez D, et al. Characterization of clinical MRSA isolates from Northern Spain and assessment of their susceptibility to phage-derived antimicrobials. Antibiotics, (2020); 9(8): 1-18.

Memon FS, Bano S, and Tunio SA. Patterns of antibiotic susceptibility and resistance in some common wound pathogens from Sukkur, Pakistan. Rawal Medical Journal, (2020); 45(2): 287-290.

Wang Y, Yuan L, Yao C, Ding L, Li C, et al. A combined toxicity study of zinc oxide nanoparticles and vitamin C in food additives. Nanoscale, (2014); 6(24): 15333-15342.

Nwaogaraku C, Smith S, and Badaki J. Non detection of mecA gene in methicillin resistant Staphylococcus aureus isolates from pigs. African Journal of Clinical and Experimental Microbiology, (2019); 20(2): 159-163.

Gergova R, Tsitou V, Gergova I, Muhtarova A, and Mitov I. Correlation of methicillin resistance and virulence genes of Staphylococcus aureus with infection types and mode of acquisition in Sofia, Bulgaria. African Journal of Clinical and Experimental Microbiology, (2019); 20(4): 280-288.

Abo-Shama UH, El-Gendy H, Mousa WS, Hamouda RA, Yousuf WE, et al. Synergistic and antagonistic effects of metal nanoparticles in combination with antibiotics against some reference strains of pathogenic microorganisms. Infection and Drug Resistance, (2020); 13(1): 351-362.

Banoee M, Seif S, Nazari ZE, Jafari‐Fesharaki P, Shahverdi HR, et al. ZnO nanoparticles enhanced antibacterial activity of ciprofloxacin against Staphylococcus aureus and Escherichia coli. Journal of Biomedical Materials Research Part B: Applied Biomaterials, (2010); 93(2): 557-561.

Ghasemi F and Jalal R. Antimicrobial action of zinc oxide nanoparticles in combination with ciprofloxacin and ceftazidime against multidrug-resistant Acinetobacter baumannii. Journal of global antimicrobial resistance, (2016); 6118-122.

Davis R and Bryson HM. Levofloxacin. Drugs, (1994); 47(4): 677-700.

Turel I, Leban I, and Bukovec Na. Crystal structure and characterization of the bismuth (III) compound with quinolone family member (ciprofloxacin). Antibacterial study. Journal of Inorganic Biochemistry, (1997); 66(4): 241-245.

Pestova E, Millichap JJ, Noskin GA, and Peterson LR. Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones. Journal of Antimicrobial Chemotherapy, (2000); 45(5): 583-590.


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