N-Acetyl-Cysteine Increases Activity of Peanut-Shaped Gold Nanoparticles Against Biofilms Formed by Clinical Strains of Pseudomonas aeruginosa Isolated from Sputum of Cystic Fibrosis Patients

Ewelina Piktel; Urszula Wnorowska; Joanna Depciuch; Dawid Łysik; Mateusz Cieśluk; Krzysztof Fiedoruk; Joanna Mystkowska; Magdalena Parlińska-Wojtan; Paul A Janmey; Robert Bucki

doi:10.2147/IDR.S348357

N-Acetyl-Cysteine Increases Activity of Peanut-Shaped Gold Nanoparticles Against Biofilms Formed by Clinical Strains of Pseudomonas aeruginosa Isolated from Sputum of Cystic Fibrosis Patients

Infect Drug Resist. 2022 Mar 5:15:851-871. doi: 10.2147/IDR.S348357. eCollection 2022.

Affiliations

¹ Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, 15-222, Poland.
² Institute of Nuclear Physic, Polish Academy of Sciences, Krakow, PL-31342, Poland.
³ Institute of Biomedical Engineering, Bialystok University of Technology, Bialystok, 15-351, Poland.
⁴ Department of Physiology and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, 19102, USA.

Abstract

Background: Extracellular polymeric substances (EPS) produced by bacteria, as they form a biofilm, determine the stability and viscoelastic properties of biofilms and prevent antibiotics from penetrating this multicellular structure. To date, studies demonstrated that an appropriate optimization of the chemistry and morphology of nanotherapeutics might provide a favorable approach to control their interaction with EPS and/or diffusion within the biofilm matrix. Targeting the biofilms' EPS, which in certain conditions can adopt liquid crystal structure, was demonstrated to improve the anti-biofilm activity of antibiotics and nanoparticles. A similar effect is achievable by interfering EPS' production by mucoactive agents, such as N-acetyl-cysteine (NAC). In our previous study, we demonstrated the nanogram efficiency of non-spherical gold nanoparticles, which due to their physicochemical features, particularly morphology, were noted to be superior in antimicrobial activity compared to their spherical-shaped counterparts.

Methods: To explore the importance of EPS matrix modulation in achieving a suitable efficiency of peanut-shaped gold nanoparticles (AuP NPs) against biofilms produced by Pseudomonas aeruginosa strains isolated from cystic fibrosis patients, fluorescence microscopy, as well as resazurin staining were employed. Rheological parameters of AuP NPs-treated biofilms were investigated by rotational and creep-recovery tests using a rheometer in a plate-plate arrangement.

Results: We demonstrated that tested nanoparticles significantly inhibit the growth of mono- and mixed-species biofilms, particularly when combined with NAC. Notably, gold nanopeanuts were shown to decrease the viscosity and increase the creep compliance of Pseudomonas biofilm, similarly to EPS-targeting NAC. Synergistic activity of AuP NPs with tobramycin was also observed, and the AuP NPs were able to eradicate bacteria within biofilms formed by tobramycin-resistant isolates.

Conclusion: We propose that peanut-shaped gold nanoparticles should be considered as a potent therapeutic agent against Pseudomonas biofilms.

Keywords: N-acetyl-cysteine; Pseudomonas aeruginosa; bacteria biofilm; cystic fibrosis; gold nanoparticles; non-spherical nanoparticles.

Grants and funding

This work was financially supported by grants from the National Science Centre, Poland: UMO-2018/30/M/NZ6/00502 (RB) and Medical University of Bialystok: SUB/1/DN/21/006/1122 (EP). Part of the study was conducted with the use of equipment purchased by the Medical University of Białystok as part of the RPOWP 2007-2013 funding, Priority I, Axis 1.1, contract No. UDA564 RPPD.01.01.00-20-001/15-00 dated 26.06.2015. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.