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Review
. 2023 Feb 2;12(2):310.
doi: 10.3390/antibiotics12020310.

Nanomaterials and Coatings for Managing Antibiotic-Resistant Biofilms

Guillem Ferreres  1 , Kristina Ivanova  1 , Ivan Ivanov  1 , Tzanko Tzanov  1
Affiliations
Review

Nanomaterials and Coatings for Managing Antibiotic-Resistant Biofilms

Guillem Ferreres et al. Antibiotics (Basel). .

Abstract

Biofilms are a global health concern responsible for 65 to 80% of the total number of acute and persistent nosocomial infections, which lead to prolonged hospitalization and a huge economic burden to the healthcare systems. Biofilms are organized assemblages of surface-bound cells, which are enclosed in a self-produced extracellular polymer matrix (EPM) of polysaccharides, nucleic acids, lipids, and proteins. The EPM holds the pathogens together and provides a functional environment, enabling adhesion to living and non-living surfaces, mechanical stability, next to enhanced tolerance to host immune responses and conventional antibiotics compared to free-floating cells. Furthermore, the close proximity of cells in biofilms facilitates the horizontal transfer of genes, which is responsible for the development of antibiotic resistance. Given the growing number and impact of resistant bacteria, there is an urgent need to design novel strategies in order to outsmart bacterial evolutionary mechanisms. Antibiotic-free approaches that attenuate virulence through interruption of quorum sensing, prevent adhesion via EPM degradation, or kill pathogens by novel mechanisms that are less likely to cause resistance have gained considerable attention in the war against biofilm infections. Thereby, nanoformulation offers significant advantages due to the enhanced antibacterial efficacy and better penetration into the biofilm compared to bulk therapeutics of the same composition. This review highlights the latest developments in the field of nanoformulated quorum-quenching actives, antiadhesives, and bactericides, and their use as colloid suspensions and coatings on medical devices to reduce the incidence of biofilm-related infections.

Keywords: antiadhesion; antimicrobial; biofilm inhibition; nanoparticles; quorum quenching; quorum sensing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Degradation of AHLs signals by quorum-quenching enzymes lactonase and acylase. (B) Schematic representation of QS process in Gram-positive and Gram-negative bacteria and different mechanisms for its inhibition. Gram-negative bacteria produce acyl-homoserine lactones (AHLs, yellow circles), while Gram-positive secrete autoinducer peptides (AIPs, green lines). When the concentration of these molecules reaches a certain threshold, the genes related with virulence and biofilm formation are expressed. Nanoformulated QQE, QSI, or metals are employed to degrade the QS signals outside the cells or block the cognate QS receptors in bacteria. (C) Inhibition of bacterial virulence by Ag NPs coated with aminocellulose and acylase I assessed through the decrease in the QS-regulated violacein production by C. violaceum (reproduced from [33] under the terms of the Creative Commons Attribution International License (CC BY 4.0)). (D) SEM images of untreated P. aeruginosa biofilm (D1) and treated with acylase loaded NPs (D2) (reproduced from [28] under the terms of the Creative Commons Attribution International License (CC BY 4.0)). (E) Light microscopic images of the untreated P. aeruginosa (E1) and S. marcescens MTCC 97 biofilms (E3), and in the presence of AuNPs synthesized using C. annuum extract (E2 and E4, respectively) (reproduced from [59] under the terms of the Creative Commons Attribution International License (CC BY 4.0)). (F) Live/dead staining assay of P. aeruginosa biofilms (F1) treated with free azithromycin (F2), and in its nanoform (F3 and F4) (Reprinted with permission from Gao et al., ‘Size and Charge Adaptive Clustered Nanoparticles Targeting the Biofilm Microenvironment for Chronic Lung Infection Management.’ ACS Nano 2020, 14, 6588–5699. Copyright 2020 American Chemical Society [45]).
Figure 2
Figure 2
(A) Schematic representation of the anti-adhesive and biofilm-dispersing strategies covered in this review. (B) Nanoaggregates of Ag-amylase degraded EPM of S. aureus biofilm on gold disks. AFM images of the disk showing EPM matrix (B1) and its disintegration by the hybrid Ag-amylase NPs (B2) (reproduced from [34] under the terms of the Creative Commons Attribution International License (CC BY 4.0)). (C) Cristal violet staining of P. aeruginosa biofilms treated with different concentrations of NO-core cross-linked star (Adapted with permission from Duong et al., ‘Nanoparticle (Star Polymer) Delivery of Nitric Oxide Effectively Negates Pseudomonas aeruginosa Biofilm Formation’. Biomacromolecules 2014, 15, 2583–2589. Copyright 2014 American Chemical Society [71]). (D) Scheme of PCBDA@Ag NPs deposition on contact lenses (D1), and confocal microscopy of P. aeruginosa grown on pristine and coated contact lenses (D2) (Reprinted from J. Colloid Interface Sci, 610, Ma et al., Commercial Soft Contact Lenses Engineered with Zwitterionic Silver Nanoparticles for Effectively Treating Microbial Keratitis 923–933, Copyright 2022, with permission from Elsevier [79]).
Figure 3
Figure 3
(A) Schematic representation of the antimicrobial mechanisms of action of bactericidal NPs covered in this review. (B) Cristal violet staining of P. aeruginosa biofilm grown on catheters coated with different concentrations of AgNPs (Reprinted from Prog. Org. Coati, 151, LewisOscar et al., ‘In vitro analysis of green fabricated silver nanoparticles (AgNPs) against Pseudomonas aeruginosa PA14 biofilm formation, their application on urinary catheter,’ 106058, Copyright 2021, with permission from Elsevier [126]). (C) Confocal microscopy images of untreated biofilm (C1) and treated with chitosan-cellobiose dehydrogenase-DNase NPs (C2) (Reprinted from Mater. Sci. Eng. C, 108, Tan et al., ‘Co-Immobilization of Cellobiose Dehydrogenase and Deoxyribonuclease I on Chitosan Nanoparticles against Fungal/Bacterial Polymicrobial Biofilms Targeting Both Biofilm Matrix and Microorganisms,’ 110499, Copyright 2019, with permission from Elsevier [124]). (D) Fluorescence microscopy images showing the grown of P. aeruginosa biofilm on pristine silicone catheters (D1) and its inhibition when the catheters were coated with self-assembled pSBMA-polymyixin B NPs (D2) (reproduced from [100] under the terms of the Creative Commons Attribution International License (CC BY 4.0)).
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