Neutralizing the Impact of the Virulence Factor LecA from Pseudomonas aeruginosa on Human Cells with New Glycomimetic Inhibitors
Abstract: Bacterial adhesion, biofilm formation and host cell invasion of the ESKAPE pathogen Pseudomonas aeruginosa require the tetravalent lectins LecA and LecB, which are therefore drug targets to fight these infections. Recently, we have reported highly potent divalent galactosides as specific LecA inhibitors. However, they suffered from very low solubility and an intrinsic chemical instability due to two acylhydrazone motifs, which precluded further biological evaluation. Here, we isosterically substituted the acylhydrazones and systematically varied linker identity and length between the two galactosides necessary for LecA binding. The optimized divalent LecA ligands showed improved stability and were up to 1000‐fold more soluble. Importantly, these properties now enabled their biological characterization. The lead compound L2 potently inhibited LecA binding to lung epithelial cells, restored wound closure in a scratch assay and reduced the invasiveness of P. aeruginosa into host cells.
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Erschienen in
-
Neutralizing the Impact of the Virulence Factor LecA from Pseudomonas aeruginosa on Human Cells with New Glycomimetic Inhibitors ; day:10 ; month:01 ; year:2023 ; extent:13
Angewandte Chemie / International edition. International edition ; (10.01.2023) (gesamt 13)
- Urheber
-
Zahorska, Eva
Rosato, Francesca
Stober, Kai
Kuhaudomlarp, Sakonwan
Meiers, Joscha
Hauck, Dirk
Reith, Dorina
Gillon, Emilie
Rox, Katharina
Imberty, Anne
Römer, Winfried
Titz, Alexander
- DOI
-
10.1002/anie.202215535
- URN
-
urn:nbn:de:101:1-2023011014201523249799
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
15.08.2025, 07:34 MESZ
Datenpartner
Dieses Objekt wird bereitgestellt von:
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Zahorska, Eva
- Rosato, Francesca
- Stober, Kai
- Kuhaudomlarp, Sakonwan
- Meiers, Joscha
- Hauck, Dirk
- Reith, Dorina
- Gillon, Emilie
- Rox, Katharina
- Imberty, Anne
- Römer, Winfried
- Titz, Alexander
Ähnliche Objekte (12)
Impedance analysis and single ion channel recordings on pore-suspending lipid bilayers based on highly ordered pore arrays
Molecular entry mechanism(s) of Pseudomonas aeruginosa : : impact of Abl kinase, LecA and Gb3
![Luftfahrt zum Anfassen ... : [eine Typen- und Erlebnisserie]](/assets/placeholder/searchResultMediaNoDigitisedMedia.png)
Luftfahrt zum Anfassen ... : [eine Typen- und Erlebnisserie]
Unraveling the role of LecA binding to single Gb3-species remodeled in artificial membrane systems determining hierarchy and constraints
Elucidation of the host cell membrane associated interaction partners of Pseudomonas aeruginosa and its lectins (in space and time)
Glycan-decorated protocells: novel features for rebuilding cellular processes
Liposomes as versatile tools: adaptation of bacteriophage therapy against intracellular bacterial pathogens by liposomal vectorization and liposomal analysis of synthetic glycolipids as surface receptors
Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation
The bacterium P. aeruginosa disperses ordered membrane domains by targeting phase boundaries
Pseudomonas aeruginosa LecB suppresses immune responses by inhibiting transendothelial migration
The Pseudomonas aeruginosa lectin LecB causes integrin internalization and inhibits epithelial wound healing
Pseudomonas aeruginosa LecB suppresses immune responses by inhibiting transendothelial migration
Impedance analysis and single ion channel recordings on pore-suspending lipid bilayers based on highly ordered pore arrays
Molecular entry mechanism(s) of Pseudomonas aeruginosa : : impact of Abl kinase, LecA and Gb3
Luftfahrt zum Anfassen ... : [eine Typen- und Erlebnisserie]
Unraveling the role of LecA binding to single Gb3-species remodeled in artificial membrane systems determining hierarchy and constraints
Elucidation of the host cell membrane associated interaction partners of Pseudomonas aeruginosa and its lectins (in space and time)
Glycan-decorated protocells: novel features for rebuilding cellular processes
Liposomes as versatile tools: adaptation of bacteriophage therapy against intracellular bacterial pathogens by liposomal vectorization and liposomal analysis of synthetic glycolipids as surface receptors
Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation
The bacterium P. aeruginosa disperses ordered membrane domains by targeting phase boundaries
Pseudomonas aeruginosa LecB suppresses immune responses by inhibiting transendothelial migration
The Pseudomonas aeruginosa lectin LecB causes integrin internalization and inhibits epithelial wound healing
Pseudomonas aeruginosa LecB suppresses immune responses by inhibiting transendothelial migration
Impedance analysis and single ion channel recordings on pore-suspending lipid bilayers based on highly ordered pore arrays
Molecular entry mechanism(s) of Pseudomonas aeruginosa : : impact of Abl kinase, LecA and Gb3
Luftfahrt zum Anfassen ... : [eine Typen- und Erlebnisserie]
Unraveling the role of LecA binding to single Gb3-species remodeled in artificial membrane systems determining hierarchy and constraints
Elucidation of the host cell membrane associated interaction partners of Pseudomonas aeruginosa and its lectins (in space and time)
Glycan-decorated protocells: novel features for rebuilding cellular processes
Liposomes as versatile tools: adaptation of bacteriophage therapy against intracellular bacterial pathogens by liposomal vectorization and liposomal analysis of synthetic glycolipids as surface receptors
Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation
The bacterium P. aeruginosa disperses ordered membrane domains by targeting phase boundaries
Pseudomonas aeruginosa LecB suppresses immune responses by inhibiting transendothelial migration
The Pseudomonas aeruginosa lectin LecB causes integrin internalization and inhibits epithelial wound healing