Targeting Bacterial Biofilm: A New LecA Multivalent Ligand with Inhibitory Activity

Abstract

Biofilm formation by bacterial pathogens is a hallmark of chronic infections and is associated to increased antibiotic tolerance that makes pathogens difficult to eradicate with conventional antibiotic therapies. Infections caused by Pseudomonas aeruginosa are of great concern, especially for immunocompromised and cystic fibrosis patients. P. aeruginosa lectins LecA and LecB are virulence factors and play a key role in establishing biofilm; therefore, inhibition of the function of these proteins has potential in dismantling the bacterium from the protective biofilm environment and in restoring the activity of antibiotics. Here, we report the NMR characterization of the binding of a galactose‐based dendrimer (Gal18) to LecA. Moreover, we demonstrate the activity of the Gal18 molecule in inhibiting P. aeruginosa biofilm formation in vitro.

Heteropolysaccharides from S. cerevisiae show anti-adhesive properties against E. coli associated with Crohn's disease

“…Similarly, depolymerization of the mannan chain into more homogenous smaller oligosaccharides did not improve the anti-adhesive activity. On the contrary, the maximum activity was decreased for all purified fractions, which strongly suggests that polymerization increasing avidity is important to reach optimal activity, as previously observed for numerous bacterial lectins, including FimH from uropathogenic E. coli and LecA from Pseudomonas aeruginosa (Palmioli, Sperandeo, Polissi, & Airoldi, 2019;Sauer et al, 2019). Thus, highly purified PPMs, irrespective of their origins, did not exhibit higher anti-adhesive potential than the intact yeasts (Sivignon, de Vallee, et al, 2015) as more than 80% of inhibition in the used experimental conditions could not be reached.…”

Synthesis of β-d-galactopyranoside-Presenting Glycoclusters, Investigation of Their Interactions with Pseudomonas aeruginosa Lectin A (PA-IL) and Evaluation of Their Anti-Adhesion Potential

“…Specifically, PA-IL displayed toxicity to respiratory epithelial cells in primary culture [10]. Due to its importance, several types of multivalent inhibitors were designed and tested against PA-IL, including fullerene-based glycoclusters [11], glycodendrimers [12], glycopeptide dendrimers [13], resorcin[4]arene-based glycoclusters [14], inhibitors based on porphyrin scaffold and β-peptoids [15], glycosylated poly(phenylacetylene)s [16], glycoconjugates based on a calix[4]arene scaffold [17,18] and on a pentaerythritol core [19]. Furthermore, the d -galactose surface-modified polymeric nanoparticles [20] and glycodendrimer micelles [21] were prepared.…”

Tubulin binding potentially clears up Bortezomib and Carfilzomib differential neurotoxic effect

“…To corroborate our in silico hypothesis we also demonstrated the direct binding of BTZ to tubulin by NMR ligand-receptor interaction studies. STD NMR is a very robust approach extensively used to detect and characterize molecular interactions between proteins, or their assemblies, and bioactive compounds 36 – 39 . Our STD experiments clearly revealed the binding of BTZ to tubulin in both its dimeric and polymeric form.…”