AFM reveals the interaction and nanoscale effects imposed by squalamine on Staphylococcus epidermidis.
Fiche publication
Date publication
avril 2023
Journal
Colloids and surfaces. B, Biointerfaces
Auteurs
Membres identifiés du Cancéropôle Est :
Mr RISLER Arnaud
Tous les auteurs :
El-Kirat-Chatel S, Varbanov M, Retourney C, Salles E, Risler A, Brunel JM, Beaussart A
Lien Pubmed
Résumé
The Gram-positive bacterium Staphylococcus epidermidis is responsible for important nosocomial infections. With the continuous emergence of antibiotic-resistant strains, the search for new treatments has been amplified in the last decades. A potential candidate against multidrug-resistant bacteria is squalamine, a natural aminosterol discovered in dogfish sharks. Despite its broad-spectrum efficiency, little is known about squalamine mode of action. Here, we used atomic force microscopy (AFM) imaging to decipher the effect of squalamine on S. epidermidis morphology, revealing the peptidoglycan structure at the bacterial surface after the drug action. Single-molecule force spectroscopy with squalamine-decorated tips shows that squalamine binds to the cell surface via the spermidine motif, most likely through electrostatic interactions between the amine groups of the molecule and the negatively-charged bacterial cell wall. We demonstrated that - although spermidine is sufficient for the initial attachment of squalamine to S. epidermidis - the integrity of the molecule needs to be conserved for its antimicrobial action. A deeper analysis of the AFM force-distance signatures suggests the implication of the accumulation-associated protein (Aap), one of the main adhesins of S. epidermidis, in the initial binding of squalamine to the bacterial cell wall. This work highlights that AFM -combined with microbiological assays at the bacterial suspension scale- is a valuable approach to better understand the molecular mechanisms behind the efficiency of squalamine antibacterial activity.
Mots clés
Aap, Aminosterol, Antimicrobial, Atomic force microscopy, Interactions, Squalamine, Staphylococcus epidermidis
Référence
Colloids Surf B Biointerfaces. 2023 04 24;226:113324