학술논문
Ceragenin-mediated disruption of Pseudomonas aeruginosa biofilms.
Document Type
Academic Journal
Author
Wnorowska U; Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland.; Łysik D; Institute of Biomedical Engineering, Bialystok University of Technology, Bialystok, Poland.; Piktel E; Independent Laboratory of Nanomedicine, Medical University of Białystok, Białystok, Poland.; Zakrzewska M; Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland.; Okła S; Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University of Kielce, Kielce, Poland.; Lesiak A; Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University of Kielce, Kielce, Poland.; Spałek J; Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University of Kielce, Kielce, Poland.; Mystkowska J; Institute of Biomedical Engineering, Bialystok University of Technology, Bialystok, Poland.; Savage PB; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.; Janmey P; Department of Physiology and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.; Fiedoruk K; Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland.; Bucki R; Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland.
Source
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Microbial biofilms, as a hallmark of cystic fibrosis (CF) lung disease and other chronic infections, remain a desirable target for antimicrobial therapy. These biopolymer-based viscoelastic structures protect pathogenic organisms from immune responses and antibiotics. Consequently, treatments directed at disrupting biofilms represent a promising strategy for combating biofilm-associated infections. In CF patients, the viscoelasticity of biofilms is determined mainly by their polymicrobial nature and species-specific traits, such as Pseudomonas aeruginosa filamentous (Pf) bacteriophages. Therefore, we examined the impact of microbicidal ceragenins (CSAs) supported by mucolytic agents-DNase I and poly-aspartic acid (pASP), on the viability and viscoelasticity of mono- and bispecies biofilms formed by Pf-positive and Pf-negative P. aeruginosa strains co-cultured with Staphylococcus aureus or Candida albicans.
Methods: The in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms' viscoelastic properties characterized by shear storage (G') and loss moduli (G"), were analyzed with a rotational rheometer.
Results: Our results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters.
Conclusion: Due to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents.
Competing Interests: Paul B. Savage and Robert Bucki are the paid consultants to N8 Medical, which focuses on commercialization of medical devices that incorporate ceragenins. The funder provided support in the form of salaries for authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2024 Wnorowska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Methods: The in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms' viscoelastic properties characterized by shear storage (G') and loss moduli (G"), were analyzed with a rotational rheometer.
Results: Our results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters.
Conclusion: Due to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents.
Competing Interests: Paul B. Savage and Robert Bucki are the paid consultants to N8 Medical, which focuses on commercialization of medical devices that incorporate ceragenins. The funder provided support in the form of salaries for authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2024 Wnorowska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)