Infection and Drug Resistance (Mar 2022)
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
Abstract
Ewelina Piktel,1 Urszula Wnorowska,1 Joanna Depciuch,2 Dawid Łysik,3 Mateusz Cieśluk,1 Krzysztof Fiedoruk,1 Joanna Mystkowska,3 Magdalena Parlińska-Wojtan,2 Paul A Janmey,4 Robert Bucki1 1Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, 15-222, Poland; 2Institute of Nuclear Physic, Polish Academy of Sciences, Krakow, PL-31342, Poland; 3Institute of Biomedical Engineering, Bialystok University of Technology, Bialystok, 15-351, Poland; 4Department of Physiology and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, 19102, USACorrespondence: Robert Bucki, Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, Bialystok, 15-222, Poland, Tel + 48 85 748 5793, Email [email protected]: 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.Graphical Abstract: Keywords: gold nanoparticles, non-spherical nanoparticles, N-acetyl-cysteine, bacteria biofilm, cystic fibrosis, Pseudomonas aeruginosa
