Abstract
The present study reports the functionalization of antibiotic-conjugated Alternanthera pungens and Trichodesma indicum copper nanoparticles (CuNPs). Initially, antibiotic profiling of multi-drug resistant (MDR) clinical isolates against five antibiotics was verified and then gentamicin and ampicillin conjugates of CuNPs were prepared. Biosynthesized nanostructures were characterized through UV–visible spectroscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction and scanning electron microscope. Biogenic synthesized CuNPs displayed highest antibacterial activity (24.0–31.3 mm inhibition zones) when capped with gentamicin as compared to the ampicillin-conjugated NPs which showed resistance against most of the bacterial species. A. pungens-derived conjugates of gentamicin (CuAp-GNT) along with the vehicle revealed 4.86 ± 0.20% and 4.25 ± 2.96% hemolytic potential and highest MDA production in S. typhimurium (3.18 ± 1.52 µg/mL and 6.31 ± 3.49 µg/mL) and K. pneumoniae (2.99 ± 0.90 µg/mL and 4.06 ± 1.20 µg/mL). Similarly, CuAp-GNT also showed highest DNA protection ability by displaying 1342.99 ± 11.87 band intensity. All-inclusive, CuAp showed more promising effects when conjugated with gentamicin indicating that capping of gentamicin with the active components of the plant-based copper nanostructures increases the antibacterial capacity of the drug. Hence, conjugation of antibiotics with bio-based sources offers great potential for identifying potent drug leads.
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References
Abd El-Wahed AA, Farag MA, Eraqi WA et al (2021) Unravelling the beehive air volatiles profile as analysed via solid-phase microextraction (SPME) and chemometrics. J King Saud Uni Sci 33(5):101449. https://doi.org/10.1016/j.jksus.2021.101449
Agarwal P, Singhal L, Gupta V, Guglani V, Chander J (2019) Vancomycin-resistant enterococci & healthcare-associated risk factors in paediatric intensive care unit. Indian J Med Res 149(1):71. https://doi.org/10.4103/ijmr.IJMR_2063_16
Alishah H, Pourseyedi S, Ebrahimipour SY, Mahani SE, Rafiei N (2016) Green synthesis of starch-mediated CuO nanoparticles: preparation, characterization, antimicrobial activities and in vitro MTT assay against MCF-7 cell line. Rend Lincei 28(1):65–71. https://doi.org/10.1007/s12210-016-0574-y
Cavassin ED, De-Figueiredo LFP, Otoch JP et al (2015) Comparison of methods to detect the in vitro activity of silver nanoparticles (AgNP) against multidrug resistant bacteria. J Nanobiotechnol 13(1):1–64. https://doi.org/10.1186/s12951-015-0120-6
Chacana J, Alizadeh S, Labelle MA et al (2017) Effect of ozonation on anaerobic digestion sludge activity and viability. Chemosphere 176:405–411. https://doi.org/10.1016/j.chemosphere.2017.02.108
Chatterjee R, Singh D, Tripathi S, Chauhan A, Aggarwal ML, Varma A (2021) Isolation and characterization of multiple drug resistant human enteric pathogens from sewage water of Delhi. Nat Environ Pollut Technol 20(2):569–578. https://doi.org/10.46488/NEPT.2021.v20i02.013
Choi J, Reipa V, Hitchins VM, Goering PL, Malinauskas RA (2011) Physicochemical characterization and in vitro hemolysis evaluation of silver nanoparticles. Toxicol Sci 123(1):133–143. https://doi.org/10.1093/toxsci/kfr149
Deb A, Vimala R (2018) Camptothecin loaded graphene oxide nanoparticle functionalized with polyethylene glycol and folic acid for anticancer drug delivery. J Drug Deliv Sci Technol 43:333–342. https://doi.org/10.1016/j.jddst.2017.10.025
Deyno S, Fekadu S, Astatkie A (2017) Resistance of Staphylococcus aureus to antimicrobial agents in Ethiopia: a meta-analysis. Antimicrob Resist Infect Control 6(1):85. https://doi.org/10.1186/s13756-017-0243-7
Gęgotek A, Skrzydlewska E (2019) Biological effect of protein modifications by lipid peroxidation products. Chem Phys Lipids 221:46–52. https://doi.org/10.1016/j.chemphyslip.2019.03.011
Giannousi K, Pantazaki A, Dendrinou-Samara C (2017) Copper-based nanoparticles as antimicrobials. Nanostruct Antimicrob Ther. https://doi.org/10.1016/B978-0-323-46152-8.00023-8
Giri L, Belwal T, Bahukhandi A et al (2017) Oxidative DNA damage protective activity and antioxidant potential of Ashtvarga species growing in the Indian Himalayan Region. Ind Crops Prod 102:173–179. https://doi.org/10.1016/j.indcrop.2017.03.023
Gounani Z, Asadollahi MA, Pedersen JN et al (2018) Mesoporous silica nanoparticles carrying multiple antibiotics provide enhanced synergistic effect and improved biocompatibility. Colloids Surf B 175:498–508. https://doi.org/10.1016/j.colsurfb.2018.12.035
Gurunathan S (2019) Rapid biological synthesis of silver nanoparticles and their enhanced antibacterial effects against Escherichia fergusonii and Streptococcus mutans. Arab J Chem 12(2):168–180. https://doi.org/10.1016/j.arabjc.2014.11.014
Hasheminya SM, Dehghannya J (2020) Green synthesis and characterization of copper nanoparticles using Eryngium caucasicum Trautv aqueous extracts and its antioxidant and antimicrobial properties. Part Sci Technol 38(8):1019–1026. https://doi.org/10.1080/02726351.2019.1658664
Hossain MS, Rana MS, Islam R, Islam AM (2018) Phenolic content analysis and evaluation of antinociceptive, antioxidant, anti-inflammatory potential of Alternanthera pungens Kunth. J Bangladesh Acad Sci 42(2):129–136. https://doi.org/10.3329/jbas.v42i2.40040
Hu W, Wu Y, Bian Y et al (2021) Joint effects of carbon nanotubes and copper oxide nanoparticles on fermentation metabolism towards Saccharofermentans acetigenes: Enhancing environmental adaptability and transcriptional expression. Bioresour Technol 336:125318. https://doi.org/10.1016/j.biortech.2021.125318
Jessop IA, Pérez YP, Jachura A et al (2021) New hybrid copper nanoparticles/conjugated polyelectrolyte composite with antibacterial activity. Polymers 13(3):401. https://doi.org/10.3390/polym13030401
Joghee S, Kalarikkal SP, Sundaram GM, Kumar TDA, Chidambaram SB (2021) Chemical profiling and in-vitro anti-inflammatory activity of bioactive fraction (s) from Trichodesma indicum (L.) R. Br. against LPS induced inflammation in RAW 264.7 murine macrophage cells. J Ethnopharmacol. https://doi.org/10.1016/j.jep.2021.114235
Kaur A, Kumar R (2019) Enhanced bactericidal efficacy of polymer stabilized silver nanoparticles in conjugation with different classes of antibiotics. RSC Adv 9(2):1095–1105. https://doi.org/10.1039/C8RA07980C
Kazmi Z, Safdar N, Chaudhry GES, Ain NU, Husnain SM, Yasmin A (2021) Radical scavenging capability influences the multifarious therapeutic tendencies of phyto-engineered CuO nanostructures. J Inorg Organomet Polym Mater 31(7):3125–3136. https://doi.org/10.1007/s10904-021-01940-3
Khorrami MB, Sadeghnia HR, Pasdar A, Ghayour-Mobarhan M, RiahiZanjani B, Darroudi M (2018) Role of pullulan in preparation of ceria nanoparticles and investigation of their biological activities. J Mol Struct 1157:127–131. https://doi.org/10.1016/j.molstruc.2017.12.053
Kiriyanthan RM, Sharmili SA, Balaji R et al (2020) Photocatalytic, antiproliferative and antimicrobial properties of copper nanoparticles synthesized using Manilkara zapota leaf extract: a photodynamic approach. Photodiagnosis Photodyn Ther 32:102058. https://doi.org/10.1016/j.pdpdt.2020.102058
Kuete V, Alibert-Franco S, Eyong K, Ngameni B, Folefoc G, Nguemeving J (2011) Antibacterial activity of some natural products against bacteria expressing a multidrug-resistant phenotype. Int J Antimicrob Agents 37:156–161. https://doi.org/10.1016/j.ijantimicag.2010.10.020
Lin YX, Zhang SN, Xue ZH et al (2019) Boosting selective nitrogen reduction to ammonia on electron-deficient copper nanoparticles. Nat Commun 10(1):1–7. https://doi.org/10.1038/s41467-019-12312-4
Liu Y, Yang Z, Wang J (2021) Fenton-like degradation of sulfamethoxazole in Cu0/Zn0-air system over abroad pH range: performance, kinetics and mechanism. Chem Eng J 403:126320. https://doi.org/10.1016/j.cej.2020.126320
Mahmoodi S, Elmi A, Hallaj-Nezhadi S (2018) Copper nanoparticles as antibacterial agents. J Mol Pharm Org Proc Res 6:1–7
Malaekeh-Nikouei B, Fazly Bazzaz BS, Mirhadi E, Tajani AS, Khameneh B (2020) The role of nanotechnology in combating biofilm-based antibiotic resistance. J Drug Deliv Sci Technol. https://doi.org/10.1016/j.jddst.2020.101880
Mesdaghinia A, Pourpak Z, Naddafi K et al (2019) An in vitro method to evaluate hemolysis of human red blood cells (RBCs) treated by airborne particulate matter (PM10). MethodsX 6:156–161. https://doi.org/10.1016/j.mex.2019.01.001
Minhas FT, Arslan G, Gubbuk IH et al (2018) Evaluation of antibacterial properties on polysulfone composite membranes using synthesized biogenic silver nanoparticles with Ulva compressa (L.) kutz. and Cladophora glomerata (L.) kutz. extracts. Int J Biol Macromol 107:157–165. https://doi.org/10.1016/j.ijbiomac.2017.08.149
Miri A, Sarani M (2018) Biosynthesis, characterization and cytotoxic activity of ceo2 nanoparticles. Ceram Int 44(11):12642–12647. https://doi.org/10.1016/j.ceramint.2018.04.063
Mukhopadhyay R, Kazi J, Debnath MC (2018) Synthesis and characterization of copper nanoparticles stabilized with Quisqualis indica extract: evaluation of its cytotoxicity and apoptosis in B16F10 melanoma cells. Biomed Pharmacother 97:1373–1385. https://doi.org/10.1016/j.biopha.2017.10.167
Murei A, Ayinde WB, Gitari MW, Samie A (2020) Functionalization and antimicrobial evaluation of ampicillin, penicillin and vancomycin with Pyrenacantha grandiflora Baill and silver nanoparticles. Sci Rep 10(1):1–14. https://doi.org/10.1038/s41598-020-68290-x
Padil VVT, Černík M (2013) Green synthesis of copper oxide nanoparticles using gum karaya as a biotemplate and their antibacterial application. Int J Nanomedicine 8:889. https://doi.org/10.2147/IJN.S40599
Palza H (2015) Antimicrobial polymers with metal nanoparticles. Int J Mol Sci 16:2099–2116. https://doi.org/10.3390/ijms16012099
Rajagopal G, Nivetha A, Sundar M et al (2021) Mixed phytochemicals mediated synthesis of copper nanoparticles for anticancer and larvicidal applications. Heliyon 7(6):e07360. https://doi.org/10.1016/j.heliyon.2021.e07360
Rajesh KM, Ajitha B, Reddy YAK, Suneetha Y, Reddy PS (2018) Assisted green synthesis of copper nanoparticles using Syzygium aromaticum bud extract: physical, optical and antimicrobial properties. Optik 154:593–600. https://doi.org/10.1016/j.ijleo.2017.10.074
Rajput V, Minkina T, Fedorenko A et al (2018) Toxicity of copper oxide nanoparticles on spring barley (Hordeum sativum distichum). Sci Total Environ 645:1103–1113. https://doi.org/10.1016/j.scitotenv.2018.07.211
Selvabai AP, Banu AS, Jeya M, Shanmugam P (2017) Characterization of methicillin resistant Staphylococcus aureus based on its virulence factors and antimicrobial susceptibility profile. Indian J Microbiol Res 4(1):74–78. https://doi.org/10.18231/2394-5478
Shankar S, Rhim JW (2014) Effect of copper salts and reducing agents on characteristics and antimicrobial activity of copper nanoparticles. Mater Lett 132:307–311. https://doi.org/10.1016/j.matlet.2014.06.014
Sharma P, Pant S, Dave V, Tak K, Sadhu V, Reddy KR (2019) Green synthesis and characterization of copper nanoparticles by Tinospora cardifolia to produce nature-friendly copper nano-coated fabric and their antimicrobial evaluation. J Microbiol Methods 160:107–116. https://doi.org/10.1016/j.mimet.2019.03.007
Singer AC, Shaw H, Rhodes V, Hart A (2016) Review of antimicrobial resistance in the environment and its relevance to environmental regulators. J Front Microbiol 7:1728. https://doi.org/10.3389/fmicb.2016.01728
Singh H, Du J, Singh P, Yi TH (2018) Extracellular synthesis of silver nanoparticles by pseudomonas sp. Thg-ls1.4 and their antimicrobial application. J Pharm Anal 8(4):258–264. https://doi.org/10.1016/j.jpha.2018.04.004
Thiruvengadam M, Chung IM, Gomathi T et al (2019) Synthesis, characterization and pharmacological potential of green synthesized copper nanoparticles. Bioproc Biosyst Eng 42(11):1769–1777. https://doi.org/10.1007/s00449-019-02173-y
Valodkar M, Rathore PS, Jadeja RN, Thounaojam M, Devkar RV, Thakore S (2012) Cytotoxicity evaluation and antimicrobial studies of starch capped water soluble copper nanoparticles. J Hazard Mater 201:244–249. https://doi.org/10.1016/j.jhazmat.2011.11.077
Wang L, Hu C, Shao L (2017) The antimicrobial activity of nanoparticles: present situation and prospects for the future. Int J Nanomedicine 12:1227. https://doi.org/10.2147/IJN.S121956
Woźniak-Budych MJ, Przysiecka Ł, Langer K et al (2017) Green synthesis of rifampicin-loaded copper nanoparticles with enhanced antimicrobial activity. J Mater Sci Mater Med 28(3):1–16. https://doi.org/10.1007/s10856-017-5857-z
Yallappa S, Manjanna J, Sindhe MA, Satyanarayan ND, Pramod SN, Nagaraja K (2013) Microwave assisted rapid synthesis and biological evaluation of stable copper nanoparticles using Terminalia arjuna bark extract. Spectrochim Acta A Mol Biomol Spectrosc 110:108–115. https://doi.org/10.1016/j.saa.2013.03.005
Yaqub A, Malkani N, Shabbir A et al (2020) Novel biosynthesis of copper nanoparticles using Zingiber and Allium sp. with synergic effect of doxycycline for anticancer and bactericidal activity. Curr Microbiol 77(9):2287–2299. https://doi.org/10.1007/s00284-020-02058-4
Yazdi MET, Modarres M, Amiri MS, Darroudi M (2019) Phyto-synthesis of silver nanoparticles using aerial extract of Salvia leriifolia Benth and evaluation of their antibacterial and photo-catalytic properties. Res Chem Intermed 45(3):1105–1116. https://doi.org/10.1007/s11164-018-3666-8
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FS: Writing–original draft, performed the experiments and data analysis. NS: Conceptualization, experimental design of the study and supervision. IF: Data curation and contributed in data revision. AY: Formal analysis, reviewing and editing the manuscript. WH: Performed the experiments and contributed to data revision.
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Saleem, F., Safdar, N., Fatima, I. et al. Functionalization of ampicillin and gentamicin with biogenic copper nanoparticles (CuNPs) remodel antimicrobial and cytotoxic outcome against MDR clinical isolates. Arch Microbiol 205, 88 (2023). https://doi.org/10.1007/s00203-023-03425-y
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DOI: https://doi.org/10.1007/s00203-023-03425-y