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
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