Enhancing the Antibacterial Activity of Erythromycin with Titanium Dioxide Nanoparticles against MRSA

Author(s): Kaleem Ullah, Shujaat A. Khan, Abdul Mannan, Romana Khan, Ghulam Murtaza*, Muhammad A. Yameen*

Journal Name: Current Pharmaceutical Biotechnology

Volume 21 , Issue 10 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Staphylococcus aureus (S. aureus) is the most common infectious agent in the community and hospitals. Infections with S. aureus are now becoming difficult to be treated by using conventional antibiotics due to its emerging methicillin-resistant S. aureus (MRSA) strain.

Objective: In the present study, MRSA was isolated from clinical samples and evaluated for resistance against different antibiotics, TiO2 nanoparticles, and their combinations.

Methods: Clinical samples were collected from Ayub Medical Complex (AMC), Abbottabad, Pakistan, and identified by different biochemical tests and polymerase chain reactions (PCR). Kirby-Bauer disk diffusion method was performed to evaluate antimicrobial susceptibility. Minimum Inhibitory Concentration (MIC) of ampicillin, ciprofloxacin, erythromycin, and vancomycin was found out by agar dilution method while the broth dilution method was used for the MIC of TiO2 nanoparticles and their combinations with erythromycin.

Results: All 13/100 (13%) MRSA were successfully identified. All isolates were susceptible to quinupristin/ dalfopristin, teicoplanin, and vancomycin, while the highest resistance was seen with erythromycin, penicillin, and tetracycline. MIC showed high resistance against ampicillin (0.25-512 mg/L) and erythromycin (0.25-1024 mg/L).

Conclusion: The MIC value of 2 mM TiO2 nanoparticles was found to be the most effective concentration after 12 h of incubation, while the combination of erythromycin with 3 mM TiO2 nanoparticles was found to be more potent which significantly lowered down the MIC of erythromycin to 2-16 mg/L.

Keywords: Titanium dioxide nanoparticles, erythromycin, methicillin-resistant Staphylococcus aureus, antibiotic susceptibility testing, minimum inhibitory concentration, MIC.

Daum, R.S. Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N. Engl. J. Med., 2007, 357(4), 380-390.
[http://dx.doi.org/10.1056/NEJMcp070747] [PMID: 17652653]
Klevens, R.M.; Morrison, M.A.; Nadle, J.; Petit, S.; Gershman, K.; Ray, S.; Harrison, L.H.; Lynfield, R.; Dumyati, G.; Townes, J.M.; Craig, A.S.; Zell, E.R.; Fosheim, G.E.; McDougal, L.K.; Carey, R.B.; Fridkin, S.K. Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA, 2007, 298(15), 1763-1771.
[http://dx.doi.org/10.1001/jama.298.15.1763] [PMID: 17940231]
Sydnor, E.R.M.; Perl, T.M. Hospital epidemiology and infection control in acute-care settings. Clin. Microbiol. Rev., 2011, 24(1), 141-173.
[http://dx.doi.org/10.1128/CMR.00027-10] [PMID: 21233510]
Liao, C.H.; Lai, C.C.; Chen, S.Y.; Huang, Y.T.; Hsueh, P.R. Strain relatedness of meticillin-resistant Staphylococcus aureus isolates recovered from patients with repeated bacteraemia. Clin. Microbiol. Infect., 2010, 16(5), 463-469.
[http://dx.doi.org/10.1111/j.1469-0691.2009.02885.x] [PMID: 19614716]
Larkin, E.A.; Carman, R.J.; Krakauer, T.; Stiles, B.G. Staphylococcus aureus: The toxic presence of a pathogen extraordinaire. Curr. Med. Chem., 2009, 16(30), 4003-4019.
[http://dx.doi.org/10.2174/092986709789352321] [PMID: 19747126]
Lina, G.; Piémont, Y.; Godail-Gamot, F.; Bes, M.; Peter, M.O.; Gauduchon, V.; Vandenesch, F.; Etienne, J. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin. Infect. Dis., 1999, 29(5), 1128-1132.
[http://dx.doi.org/10.1086/313461] [PMID: 10524952]
Sakoulas, G.; Moise-Broder, P.A.; Schentag, J.; Forrest, A.; Moellering, R.C., Jr; Eliopoulos, G.M. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J. Clin. Microbiol., 2004, 42(6), 2398-2402.
[http://dx.doi.org/10.1128/JCM.42.6.2398-2402.2004] [PMID: 15184410]
Davies, J.; Davies, D. Origins and evolution of antibiotic resistance. Microbiol. Mol. Biol. Rev., 2010, 74(3), 417-433.
[http://dx.doi.org/10.1128/MMBR.00016-10] [PMID: 20805405]
Felten, A.; Grandry, B.; Lagrange, P.H.; Casin, I. Evaluation of three techniques for detection of low-level Methicillin-Resistant Staphylococcus aureus (MRSA): A disk diffusion method with cefoxitin and moxalactam, the Vitek 2 system, and the MRSA-screen latex agglutination test. J. Clin. Microbiol., 2002, 40(8), 2766-2771.
[http://dx.doi.org/10.1128/JCM.40.8.2766-2771.2002] [PMID: 12149327]
Haghi, M.; Hekmatafshar, M.; Janipour, M.B.; Seyyed, S. Antibacterial effect of TiO2 nanoparticles on pathogenic strain of E. coli. Int. J. Adv. Biotechnol. Res., 2012, 3(3), 621-624.
Wu, X.; Liu, H.; Liu, J.; Haley, K.N.; Treadway, J.A.; Larson, J.P.; Ge, N.; Peale, F.; Bruchez, M.P. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat. Biotechnol., 2003, 21(1), 41-46.
[http://dx.doi.org/10.1038/nbt764] [PMID: 12459735]
Sungkaworn, T.; Triampo, W.; Nalakarn, P.; Triampo, D.; Tang, I.M.; Lenbury, Y. The Effects of TiO2 Nanoparticles on tumor cell colonies: Fractal dimension and morphological properties. Int. J. Biomed. Sci., 2007, 2(1), 67-74.
Rengifo-Herrera, J.A.; Pierzchała, K.; Sienkiewicz, A.; Forró, L.; Kiwi, J.; Pulgarin, C. Abatement of organics and Escherichia coli by N, S co-doped TiO2 under UV and visible light. Implications of the formation of singlet oxygen (1O2) under visible light. Appl. Catal. B, 2009, 88(3-4), 398-406.
Kato, H.; Kudo, A. Visible-light-response and photocatalytic activities of TiO2 and SrTiO3 photocatalysts codoped with antimony and chromium. J. Phys. Chem. B, 2002, 106(19), 5029-5034.
Murakami, K.; Minamide, W.; Wada, K.; Nakamura, E.; Teraoka, H.; Watanabe, S. Identification of methicillin-resistant strains of staphylococci by polymerase chain reaction. J. Clin. Microbiol., 1991, 29(10), 2240-2244.
[PMID: 1939577]
Brakstad, O.G.; Aasbakk, K.; Maeland, J.A. Detection of Staphylococcus aureus by polymerase chain reaction amplification of the nuc gene. J. Clin. Microbiol., 1992, 30(7), 1654-1660.
[PMID: 1629319]
Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. Clinical and Laboratory Standards Institute, 2013, 32, 1-184.
Khan, R.; Kim, S.W.; Kim, T-J.; Lee, H. A novel acid-base catalyzed sol-gel synthesis of highly active mesoporous TiO2 photocatalystst. Bull. Korean Chem. Soc., 2007, 28(11), 1951-1957.
Chakraborty, S.; Afaq, N.; Singh, N.; Majumdar, S. Antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus. J. Integr. Med., 2018, 16(5), 350-357.
[http://dx.doi.org/10.1016/j.joim.2018.07.005] [PMID: 30120078]
Witte, W.; Kresken, M.; Braulke, C.; Cuny, C. Increasing incidence and widespread dissemination of Methicillin-Resistant Staphylococcus aureus (MRSA) in hospitals in central Europe, with special reference to German hospitals. Clin. Microbiol. Infect., 1997, 3(4), 414-422.
[http://dx.doi.org/10.1111/j.1469-0691.1997.tb00277.x] [PMID: 11864151]
Skov, R.; Smyth, R.; Larsen, A.R.; Bolmstrôm, A.; Karlsson, A.; Mills, K.; Frimodt-Moller, N.; Kahlmeter, G. Phenotypic detection of methicillin resistance in Staphylococcus aureus by disk diffusion testing and Etest on Mueller-Hinton agar. J. Clin. Microbiol., 2006, 44(12), 4395-4399.
[http://dx.doi.org/10.1128/JCM.01411-06] [PMID: 17050809]
Bukhari, S.Z.; Ahmed, S.; Zia, N. Antimicrobial susceptibility pattern of Staphylococcus aureus on clinical isolates and efficacy of laboratory tests to diagnose MRSA: A multi-centre study. J. Ayub Med. Coll. Abbottabad, 2011, 23(1), 139-142.
[PMID: 22830169]
Lim, K.T.; Hanifah, Y.A.; Yusof, M.; Thong, K.L. ermA, ermC, tetM and tetK are essential for erythromycin and tetracycline resistance among methicillin-resistant Staphylococcus aureus strains isolated from a tertiary hospital in Malaysia. Indian J. Med. Microbiol., 2012, 30(2), 203-207.
[http://dx.doi.org/10.4103/0255-0857.96693] [PMID: 22664438]
Roy, A.S. Effect of Nano - Titanium Dioxide with Different Antibiotics against Methicillin-Resistant Staphylococcus aureus. J. Biomater. Nanobiotechnol., 2010, 1(1), 37-41.
Desai, V.S.; Kowshik, M. Antimicrobial activity of titanium dioxide nanoparticles synthesized by Sol-Gel technique. Res. J. Microbiol., 2009, 4, 97-103.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 07 September, 2020
Page: [948 - 954]
Pages: 7
DOI: 10.2174/1389201021666200128124142

Article Metrics

PDF: 34