Inhibition of Staphylococcus aureus biofilm-forming functional amyloid by molecular tweezers
Autor: | Thomas Schrader, Yasser B. Ruiz-Blanco, Joel Mieres-Perez, Nir Salinas, James M. Gibson, Orit Malka, Elsa Sanchez-Garcia, Angela Bailey Eden, Gal Bitan, Raz Jelinek, Meytal Landau, Ravit Malishev, Sofiya Kolusheva, Chunyu Wang, Frank-Gerrit Klärner |
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Rok vydání: | 2021 |
Předmět: |
Amyloid
Staphylococcus aureus Optical Tweezers Bacterial Toxins Clinical Biochemistry Chemie Virulence Peptide binding Peptide Microbial Sensitivity Tests MRSA molecular tweezer Neurodegenerative Biology medicine.disease_cause PSMa1 01 natural sciences Biochemistry Article biofilm Hemolysin Proteins Drug Discovery medicine 2.2 Factors relating to the physical environment Aetiology Molecular Biology amyloid peptides Pharmacology chemistry.chemical_classification 010405 organic chemistry Biofilm functional amyloid Pathogenic bacteria biochemical phenomena metabolism and nutrition biology.organism_classification Anti-Bacterial Agents 0104 chemical sciences antibacterial Emerging Infectious Diseases Infectious Diseases chemistry Biofilms phenol-soluble modulins Biophysics Molecular Medicine Infection Molecular tweezers Bacteria |
Zdroj: | Cell chemical biology, vol 28, iss 9 Cell Chem Biol |
ISSN: | 2451-9456 |
DOI: | 10.1016/j.chembiol.2021.03.013 |
Popis: | Biofilms are rigid and largely impenetrable three-dimensional matrices constituting virulence determinants of various pathogenic bacteria. Here, we demonstrate that molecular tweezers, unique supramolecular artificial receptors, modulate biofilm formation of Staphylococcus aureus. In particular, the tweezers affect the structural and assembly properties of phenol-soluble modulin α1 (PSMα1), a biofilm-scaffolding functional amyloid peptide secreted by S. aureus. The data reveal that CLR01, a diphosphate tweezer, exhibits significant S. aureus biofilm inhibition and disrupts PSMα1 self-assembly and fibrillation, likely through inclusion of lysine side chains of the peptide. In comparison, different peptide binding occurs in the case of CLR05, a tweezer containing methylenecarboxylate units, which exhibits lower affinity for the lysine residues yet disrupts S. aureus biofilm more strongly than CLR01. Our study points to a possible role for molecular tweezers as potent biofilm inhibitors and antibacterial agents, particularly against untreatable biofilm-forming and PSM-producing bacteria, such as methicillin-resistant S. aureus. |
Databáze: | OpenAIRE |
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