Abstract
The discovery of antibiotics in the twentieth century made it possible to treat bacterial infections and revolutionized modern medicine. However, gradually, it is possible to perceive a decrease in the effectiveness of antimicrobial agents against pathogenic isolates, which, together with the low investment in the discovery and/or development of new antibiotics by large pharmaceutical companies since the 1960s, makes it increasingly difficult to treatment of infections caused by these microorganisms. The search for strategies capable of potentiating the effect of existing drugs through the development of new therapeutic approaches, which also have the potential to circumvent bacterial resistance to antibiotics, has become indispensable. In this context, metallic nanoparticles stand out, as they could be used to act synergistically with drugs. Thus, the objective of this review was to present the latest information on the synergistic activity of antibiotics with metallic nanoparticles, pointing out this association as a promising alternative for the preservation of bacterial sensitivity to these drugs. The different metallic nanoparticles can present different benefits in the treatment of bacterial infections, with this being able to potentiate the bacterial activity of antibiotics that are widely used in the clinic, being able to increase the susceptibility in multiresistant microorganisms.
Key points
• Metallic nanoparticles increased the antimicrobial action of drugs;
• Metallic nanoparticles compromise the action of bacterial efflux pumps;
• Biofilm formation was inhibited after treatment with metallic nanoparticles.
Similar content being viewed by others
References
Abo-Shama UH, El-Gendy H, Mousa WS, Hamouda RA, Yousuf WE, Hetta HF, Abdeen EE (2020) Synergistic and antagonistic effects of metal nanoparticles in combination with antibiotics against some reference strains of pathogenic microorganisms. Infect Drug Resist 13:351–362. https://doi.org/10.2147/idr.s234425
Abo-zeid Y, Amer A, El-Houssieny B, Mahmoud M, Sakran W (2021) Overview on bacterial resistance and nanoparticles to overcome bacterial resistance. J Adv Pharm Res. https://doi.org/10.21608/aprh.2021.76488.1131
Allahverdiyev AM, Kon K, Abamor ES, Bagirova M, Rafailovich M (2011) Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents. Expert Rev Anti Infect Ther 9:1035–1052. https://doi.org/10.1586/eri.11.121
Aremu OS, Qwebani-Ogunleye T, Katata-Seru L, Mkhize Z, Trant JF (2021) Synergistic broad-spectrum antibacterial activity of Hypoxis hemerocallidea-derived silver nanoparticles and streptomycin against respiratory pathobionts. Sci Rep 11:15222. https://doi.org/10.1038/s41598-021-93978-z
Arya SS, Sharma MM, Das RK, Rookes J, Cahill D, Lenka SK (2019) Vanillin mediated green synthesis and application of gold nanoparticles for reversal of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates. Heliyon 5:e02021. https://doi.org/10.1016/j.heliyon.2019.e02021
Ashajyothi C, Harish KH, Dubey N, Chandrakanth RK (2016) Antibiofilm activity of biogenic copper and zinc oxide nanoparticles-antimicrobials collegiate against multiple drug resistant bacteria: a nanoscale approach. J Nanostructure Chem 6:329–341. https://doi.org/10.1007/s40097-016-0205-2
Baker S, Pasha A, Satish S (2017) Biogenic nanoparticles bearing antibacterial activity and their synergistic effect with broad spectrum antibiotics: emerging strategy to combat drug resistant pathogens. Saudi Pharm J 25:44–51. https://doi.org/10.1016/j.jsps.2015.06.011
Blecher K, Nasir A, Friedman A (2011) The growing role of nanotechnology in combating infectious disease. Virulence 2:395–401. https://doi.org/10.4161/viru.2.5.17035
Borase HP, Patil CD, Suryawanshi RK, Koli SH, Mohite BV, Benelli G, Patil SV (2017) Mechanistic approach for fabrication of gold nanoparticles by Nitzschia diatom and their antibacterial activity. Bioprocess Biosyst Eng 40:1437–1446. https://doi.org/10.1007/s00449-017-1801-3
Burygin G, Khlebtsov B, Shantrokha A, Dykman L, Bogatyrev V, Khlebtsov N (2009) On the enhanced antibacterial activity of antibiotics mixed with gold nanoparticles. Nanoscale Res Lett 4:794–801. https://doi.org/10.1007/s11671-009-9316-8
Cavalcanti IMF, Menezes TGC, Campos LA de A, Ferraz MS, Maciel MAV, Caetano MNP, Santos-Magalhães NS (2018) Interaction study between vancomycin and liposomes containing natural compounds against methicillin-resistant Staphylococcus aureus clinical isolates. Braz J Pharm Sci 54: e00203. https://doi.org/10.1590/s2175-97902018000200203
Coates ARM, Hu Y, Holt J, Ye P (2020) Antibiotic combination therapy against resistant bacterial infections: synergy, rejuvenation and resistance reduction. In: Expert Rev Anti Infect Ther. 18:5–15. https://doi.org/10.1080/14787210.2020.1705155.
Costa Júnior SD, da Silva WRC, da Silva AMCM, Maciel MAV, Cavalcanti IMF (2020) Synergistic effect between usnic acid and polymyxin B against resistant clinical isolates of Pseudomonas aeruginosa. Evid Based Complementary Altern Med 2020:e9852145. https://doi.org/10.1155/2020/9852145
El Domany EB, Tamer M. E, Ahmed AE, Farghli AA (2018) Biosynthesis, characterization, antibacterial and synergistic effect of silver nanoparticles using Fusarium oxysporum. J Pure Appl Microbiol 11(3):1441–1446. https://doi.org/10.22207/JPAM.11.3.27
Espitia PJP, de Fatima Ferreira Soares N, dos Reis Coimbra JS, de Andrade NJ, Cruz RS, Medeiros EAA (2012) Zinc oxide nanoparticles: synthesis, antimicrobial activity and food packaging applications. Food Bioproc Tech 5:1447–1464. https://doi.org/10.1007/s11947-012-0797-6
Franci G, Falanga A, Galdiero S, Palomba L, Rai M, Morelli G, Galdiero M (2015) Silver nanoparticles as potential antibacterial agents. Molecules 20:8856–8874. https://doi.org/10.3390/molecules20058856
Frei A, Zuegg J, Elliott AG, Baker M, Braese S, Brown C, Chen F, Dowson CG, Dujardin G, Jung N, King AP, Mansour AM, Massi M, Moat J, Mohamed HA, Renfrew AK, Rutledge PJ, Sadler PJ, Todd MH, Willans CE (2020) Metal complexes as a promising source for new antibiotics. Chem Sci 11:2627–2639. https://doi.org/10.1039/c9sc06460e
González-Bello C (2017) Antibiotic adjuvants – a strategy to unlock bacterial resistance to antibiotics. Bioorganic Med Chem Lett 27:4221–4228. https://doi.org/10.1016/j.bmcl.2017.08.027
Habash MB, Goodyear MC, Park AJ, Surette MD, Vis EC, Harris RJ, Khursigara CM (2017) Potentiation of tobramycin by silver nanoparticles against Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 61:e00415-17. https://doi.org/10.1128/aac.00415-17
Hutchings MI, Truman AW, Wilkinson B (2019) Antibiotics: past, present and future. Curr Opin Microbiol 51:72–80. https://doi.org/10.1016/j.mib.2019.10.008
Ingle AP, Duran N, Rai M (2013) Bioactivity, mechanism of action, and cytotoxicity of copper-based nanoparticles: a review. Appl Microbiol Biotechnol 98:1001–1009. https://doi.org/10.1007/s00253-013-5422-8
Keshari A, Srivastava R, Yadav S, Nath G, Gond S (2020) synergistic activity of green silver nanoparticles with antibiotics. J Nanomed Res 5:44–54. https://doi.org/10.22034/nmrj.2020.01.006
Khameneh B, Diab R, Ghazvini K, Fazly Bazzaz BS (2016) Breakthroughs in bacterial resistance mechanisms and the potential ways to combat them. Microb Pathog 95:32–42. https://doi.org/10.1016/j.micpath.2016.02.009
Kim JS, Kuk E, Yu KN, Kim J-H, Park SJ, Lee HJ, Kim SH, Park YK, Park YH, Hwang C-Y, Kim Y-K, Lee Y-S, Jeong DH, Cho M-H (2007) Antimicrobial effects of silver nanoparticles. Nanomed Nanotechnol Biol Med 3:95–101. https://doi.org/10.1016/j.nano.2006.12.001
Kumar M, Jaiswal S, Sodhi KK, Shree P, Singh DK, Agrawal PK, Shukla P (2019) Antibiotics bioremediation: perspectives on its ecotoxicity and resistance. Environ Int 124:448–461. https://doi.org/10.1016/j.envint.2018.12.065
Kumar S, Varela MF (2013) Molecular mechanisms of bacterial resistance to antimicrobial agents. In: Microbial pathogens and strategies for combating them: science, technology and education. Formatex Research Center 4:522–534
Kurup RS, Cherian E, Thomas PC (2018) Synthesis of ZnO nanoparticle and evaluation of its potential to enhance the activity of antibiotics. IOP Conf Ser Mater Sci Eng 360:012001. https://doi.org/10.1088/1757-899x/360/1/012001
Lee B, Lee DG (2019) Synergistic antibacterial activity of gold nanoparticles caused by apoptosis-like death. J Appl Microbiol 127:701–712. https://doi.org/10.1111/jam.14357
Lee N-Y, Ko W-C, Hsueh P-R (2019) Nanoparticles in the treatment of infections caused by multidrug-resistant organisms. Front Pharmacol 10:1153. https://doi.org/10.3389/fphar.2019.01153
Lopez-Carrizales M, Velasco K, Castillo C, Flores A, Magaña M, Martinez-Castanon G, Martinez-Gutierrez F (2018) In vitro synergism of silver nanoparticles with antibiotics as an alternative treatment in multiresistant uropathogens. Antibiotics 7:50. https://doi.org/10.3390/antibiotics7020050
Machowska A, StålsbyLundborg C (2018) Drivers of irrational use of antibiotics in Europe. Int J Environ Res Public Health 16:27. https://doi.org/10.3390/ijerph16010027
Mohanraj VJ, Chen Y (2007) Nanoparticles - a review. Trop J Pharm Res 5:561–573. https://doi.org/10.4314/tjpr.v5i1.14634
Moteriya P, Chanda S (2018) Biosynthesis of silver nanoparticles formation from Caesalpinia pulcherrima stem metabolites and their broad spectrum biological activities. J Genet Eng Biotechnol 16:105–113. https://doi.org/10.1016/j.jgeb.2017.12.003
Murugan S (2018) Investigation of the synergistic antibacterial action of copper nanoparticles on certain antibiotics against human pathogens. Int J Pharm Pharm Sci 10:83. https://doi.org/10.22159/ijpps.2018v10i10.28069
do Nascimento PPS, de Siqueira Ferraz-Carvalho R, da Silva TS, de Sousa Araújo TA, de Amorim ELC, Pereira MA, Cavalcanti IMF (2021) Interaction between bark extract of Anadenanthera colubrina var. cebil (Griseb) Altschul with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA). Res Soc Dev 10:e14210615469–e14210615469. https://doi.org/10.33448/rsd-v10i6.15469
Naqvi SS, Anwer H, Siddiqui A, Zohra RR, Ali SA, Shah MR, Hashim S (2021) Novel synthesis of maltol capped copper nanoparticles and their synergistic antibacterial activity with antibiotics. Plasmonics 16:1915–1928. https://doi.org/10.1007/s11468-021-01452-3
Nikparast Y, Saliani M (2018) Synergistic effect between phyto-syntesized silver nanoparticles and ciprofloxacin antibiotic on some pathogenic bacterial strains. J Med Bacteriol 7:36–43
Niño-Martínez N, Salas Orozco MF, Martínez-Castañón G-A, Torres Méndez F, Ruiz F (2019) Molecular mechanisms of bacterial resistance to metal and metal oxide nanoparticles. Int J Mol Sci 20:2808. https://doi.org/10.3390/ijms20112808
Padalia H, Moteriya P, Chanda S (2017) Synergistic antimicrobial and cytotoxic potential of zinc oxide nanoparticles synthesized using Cassia auriculata leaf extract. BioNanoScience 8:196–206. https://doi.org/10.1007/s12668-017-0463-6
Pallela PNVK, Ruddaraju LK, Veerla SC, Matangi R, Kollu P, Ummey S, Pammi SVN (2020) Synergetic antibacterial potential, dye degrading capability and biocompatibility of Asperagus racemosus root assisted ZnO nanoparticles. Mater Today Commun 25:101574. https://doi.org/10.1016/j.mtcomm.2020.101574
Prabhjot K, Nene A, Sharma D, Somani PR, Tuli HS (2019) Synergistic effect of copper nanoparticles and antibiotics to enhance antibacterial potential. Bio-Mat Tech 1:33–47
Ramasami N, S M, S JP, P P (2019) Green synthesis and characterization of bioinspired silver, gold and platinum nanoparticles and evaluation of their synergistic antibacterial activity after combining with different classes of antibiotics. Mater Sci Eng C 96:693–707 https://doi.org/10.1016/j.msec.2018.11.050
Regea G (2018) Review on antibiotics resistance and its economic impacts. J of Pharmacol and Clin Res 5:JPCR.MS.ID. 555675. https://doi.org/10.19080/JPCR.2018.05.555675
Ruddaraju LK, Pammi SVN, Pallela PNVK, Padavala VS, Kolapalli VRM (2019) Antibiotic potentiation and anti-cancer competence through bio-mediated ZnO nanoparticles. Mater Sci Eng C 103:109756. https://doi.org/10.1016/j.msec.2019.109756
Sabir S, Arshad M, Chaudhari SK (2014) Zinc oxide nanoparticles for revolutionizing agriculture: synthesis and applications. Sci World J 2014:1–8. https://doi.org/10.1155/2014/925494
Sánchez-Sanhueza G, Fuentes-Rodríguez D, Bello-Toledo H (2016) Copper nanoparticles as potential antimicrobial agent in disinfecting root canals: a systematic review. Int J Odontostomat 10:547–554. https://doi.org/10.4067/s0718-381x2016000300024
Santos EMP, Martins CCB, de Oliveira Santos JV, da Silva WRC, Silva SBC, Pelagio-Flores MA, Galembeck A, Cavalcanti IMF (2021) Silver nanoparticles-chitosan composites activity against resistant bacteria: tolerance and biofilm inhibition. J Nanopart Res: Interdisciplinary Forum Nanoscale Sci Technol 23:196. https://doi.org/10.1007/s11051-021-05314-1
Satapathy S, Kumar S, Sukhdane KS, Shukla SP (2017) Biogenic synthesis and characterization of silver nanoparticles and their effects against bloom-forming algae and synergistic effect with antibiotics against fish pathogenic bacteria. J Appl Phycol 29:1865–1875. https://doi.org/10.1007/s10811-017-1091-9
Patel S, Singh D, Singh MR, Chauhan NS (2017) Nanoparticles as a platform for antimicrobial drug delivery. Adv Pharmacol Pharm 5:31–43. https://doi.org/10.13189/app.2017.050301
Shaikh S, Nazam N, Rizvi SMD, Ahmad K, Baig MH, Lee EJ, Choi I (2019) Mechanistic insights into the antimicrobial actions of metallic nanoparticles and their implications for multidrug resistance. Int J Mol Sci 20:2468. https://doi.org/10.3390/ijms20102468
Singh A, Gautam PK, Verma A, Singh V, Shivapriya PM, Shivalkar S, Sahoo AK, Samanta SK (2020) Green synthesis of metallic nanoparticles as effective alternatives to treat antibiotics resistant bacterial infections: a review. Biotechnol Rep 25:e00427. https://doi.org/10.1016/j.btre.2020.e00427
Singh T, Jyoti K, Patnaik A, Singh A, Chauhan SC (2018) Spectroscopic, microscopic characterization of Cannabis sativa leaf extract mediated silver nanoparticles and their synergistic effect with antibiotics against human pathogen. Alex Eng J 57:3043–3051. https://doi.org/10.1016/j.aej.2018.04.002
Sirelkhatim A, Mahmud S, Seeni A, Kaus NHM, Ann LC, Bakhori SKM, Hasan H, Mohamad D (2015) Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nano-Micro Lett 7:219–242. https://doi.org/10.1007/s40820-015-0040-x
Sultan I, Rahman S, Jan AT, Siddiqui MT, Mondal AH, Haq QMR (2018) Antibiotics, resistome and resistance mechanisms: a bacterial perspective. Front Microbiol 9:2066. https://doi.org/10.3389/fmicb.2018.02066
Vazquez-Muñoz R, Meza-Villezcas A, Fournier PGJ, Soria-Castro E, Juarez-Moreno K, Gallego-Hernández AL, Bogdanchikova N, Vazquez-Duhalt R, Huerta-Saquero A (2019) Enhancement of antibiotics antimicrobial activity due to the silver nanoparticles impact on the cell membrane. PLoS ONE 14:e0224904. https://doi.org/10.1371/journal.pone.0224904
Wright GD (2016) Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol 24:862–871. https://doi.org/10.1016/j.tim.2016.06.009
Xie Y, He Y, Irwin PL, Jin T, Shi X (2011) Antibacterial activity and mechanism of action of zinc oxide nanoparticles against Campylobacter jejuni. Appl Environ Microbiol 77:2325–2331. https://doi.org/10.1128/aem.02149-10
Yaqub A, Malkani N, Shabbir A, Ditta SA, Tanvir F, Ali S, Naz M, Kazmi SAR, Ullah R (2020) Novel biosynthesis of copper nanoparticles using Zingiber and Allium sp. with synergic effect of doxycycline for anticancer and bactericidal activity. Curr Microbiol 77:2287–2299. https://doi.org/10.1007/s00284-020-02058-4
Zharov VP, Mercer KE, Galitovskaya EN, Smeltzer MS (2006) Photothermal nanotherapeutics and nanodiagnostics for selective killing of bacteria targeted with gold nanoparticles. Biophys J 90:619–627. https://doi.org/10.1529/biophysj.105.061895
Funding
Maria Anndressa Alves Agreles thanks the Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE) for the Scientific Initiation grant (PIBIC).
This study was partially funded by the National Council for Scientific and Technological Development (CNPq) (426,065/2018–2).
Author information
Authors and Affiliations
Contributions
MAAA, IDLC, and IMFC: participated in all stages from study design of the review to the final version of the article.
Corresponding author
Ethics declarations
Ethics approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Competing interests
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Agreles, M.A.A., Cavalcanti, I.D.L. & Cavalcanti, I.M.F. Synergism between metallic nanoparticles and antibiotics. Appl Microbiol Biotechnol 106, 3973–3984 (2022). https://doi.org/10.1007/s00253-022-12001-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-022-12001-1