Magnetic Nanoconjugated Teicoplanin: A Novel Tool for Bacterial Infection Site Targeting

Abstract

Nanoconjugated antibiotics can be regarded as next-generation drugs as they possess remarkable potential to overcome multidrug resistance in pathogenic bacteria. Iron oxide nanoparticles (IONPs) have been extensively used in the biomedical field because of their biocompatibility and magnetic properties. More recently, IONPs have been investigated as potential nanocarriers for antibiotics to be magnetically directed to/recovered from infection sites. Here, we conjugated the “last-resort” glycopeptide antibiotic teicoplanin to IONPs after surface functionalization with (3-aminopropyl) triethoxysilane (APTES). Classical microbiological methods and fluorescence and electron microscopy analysis were used to compare antimicrobial activity and surface interactions of naked IONPs, amino-functionalized NPs (NP-APTES), and nanoconjugated teicoplanin (NP-TEICO) with non-conjugated teicoplanin. As bacterial models, differently resistant strains of three Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis) and a Gram-negative representative (Escherichia coli) were used. The results indicated that teicoplanin conjugation conferred a valuable and prolonged antimicrobial activity to IONPs toward Gram-positive bacteria. No antimicrobial activity was detected using NP-TEICO toward the Gram-negative E. coli. Although IONPs and NP-APTES showed only insignificant antimicrobial activity in comparison to NP-TEICO, our data indicate that they might establish diverse interaction patterns at bacterial surfaces. Sensitivity of bacteria to NPs varied according to the surface provided by the bacteria and it was species specific. In addition, conjugation of teicoplanin improved the cytocompatibility of IONPs toward two human cell lines. Finally, NP-TEICO inhibited the formation of S. aureus biofilm, conserving the activity of non-conjugated teicoplanin versus planktonic cells and improving it toward adherent cells.

New Molecular Tools for Regulation and Improvement of A40926 Glycopeptide Antibiotic Production in Nonomuraea gerenzanensis ATCC 39727

“…The urgent need for new potent antibiotics has driven much recent interest in GPAs. For example, chemical synthesis recently resulted in the generation of a plethora of vancomycin derivatives with novel modifications that show superior antimicrobial activities (Okano et al, 2017;Wu and Boger, 2019), while teicoplanin has been conjugated with nanoparticles resulting in increased activity against biofilm-forming pathogens (Armenia et al, 2018).…”

Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm

“…Although many authors have previously reported that IONPs, as well as other types of metal oxide NPs, possess an intrinsic antimicrobial activity (Gabrielyan et al, 2019;Das et al, 2020;Shkodenko et al, 2020), in the different experiments hereby conducted (i.e., agar diffusion assay, BacLight fluorescence assay, bacterial growth kinetics, CFU measurement) a significant bacteriostatic and bactericidal activity was conferred to IONPs only following their conjugation with teicoplanin and vancomycin. As previously reported (Ebrahiminezhad et al, 2014;Arakha et al, 2015;Dinali et al, 2017;Armenia et al, 2018), naked IONPs can interact mainly via electrostatic interactions with bacterial cell envelopes, arresting transiently cell growth and, in sporadic cases, causing cell death, but this phenomenon greatly differs in magnitude from the potent and selective antimicrobial action of 'last-resort' antibiotics such as GPAs towards Gram-positive bacterial strains. In a recent review, Shkodenko et al (2020) reported that in general naked IONPs have to be used at mg/l concentrations to show some antibacterial activity.…”

“…The antimicrobial potential of nanocarried teicoplanin was reported only by Peng et al (2010) , who treated osteomyelitis with teicoplanin-encapsulated biodegradable thermosensitive hydrogel; by Gonzalez Gomez et al (2019) , who tested liposome-encapsulated teicoplanin towards S. aureus ; and by Ucak et al (2020) , who reported teicoplanin delivery in poly lactic-co-glycolic acid NPs functionalized with S. aureus specific aptamers. In 2018, our group succeeded for the first time in conjugating teicoplanin to magnetic IONPs, after their functionalization with (3-aminopropyl) triethoxysilane (APTES; Armenia et al, 2018 ). In the present paper, we have investigated the synthesis and the efficacy of IONPs carrying vancomycin and teicoplanin, as an innovative system for GPA formulation and use.…”

Nanomedicines for the Efficient Treatment of Intracellular Bacteria: The “ART” Principle

“…It is worth noted that in vitro guidance can also realize the infection targeting of nanomedicines ( Yu et al, 2020 ). As an example, magnetic targeting has been recently introduced to enhance the accumulation of nanomedicines at infection sites ( Subbiahdoss et al, 2012 ; Armenia et al, 2018 ). Ji et al utilize the magnetic targeting ability of magnetic nanoparticles to deliver glucose oxidase, efficiently eradicating bacterial/fungi biofilms ( Ji et al, 2021 ).…”