A LecA Ligand Identified from a Galactoside‐Conjugate Array Inhibits Host Cell Invasion by <i>Pseudomonas aeruginosa</i>

Novoa, Alexandre; Eierhoff, Thorsten; Topin, Jérémie; Varrot, A.; Barluenga, Sofía; Imberty, Anne; Römer, Winfried; Winssinger, Nicolas

doi:10.1002/anie.201402831

Cited by 85 publications

(110 citation statements)

References 35 publications

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“…16 Inhibition of LecA with synthetic ligands can be achieved with high affinity oligogalactosylated ligands. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] High binding can be obtained thanks to the so called glycoside cluster effect. 32,33 The design of multivalent ligands targeting LecA has been recently reviewed.…”

Section: Introductionmentioning

confidence: 99%

Mannose-centered aromatic galactoclusters inhibit the biofilm formation of Pseudomonas aeruginosa

et al. 2015

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Pseudomonas aeruginosa (PA) is a major public health care issue due to its ability to develop antibiotic resistance mainly through adhesion and biofilm formation. Therefore, targeting the bacterial molecular arsenal involved in its adhesion and the formation of its biofilm appears as a promising tool against this pathogen. The galactose-binding LecA (or PA-IL) has been described as one of the PA virulence factors involved in these processes. Herein, the affinity of three tetravalent mannose-centered galactoclusters toward LecA was evaluated with five different bioanalytical methods: HIA, ELLA, SPR, ITC and DNA-based glycoarray. Inhibitory potential towards biofilms was then assessed for the two glycoclusters with highest affinity towards LecA (Kd values of 157 and 194 nM from ITC measurements). An inhibition of biofilm formation of 40% was found for these galactoclusters at 10 μM concentration. Applications of these macromolecules in anti-bacterial therapy are therefore possible through an anti-adhesive strategy.

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Section: Introductionmentioning

confidence: 99%

Mannose-centered aromatic galactoclusters inhibit the biofilm formation of Pseudomonas aeruginosa

et al. 2015

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“…1). 36,[44][45][46][47][48][49][50] We reasoned that this method could allow us to discriminate between covalent and non-covalent ligands using a denaturing wash that would denature proteins and compromise noncovalent ligand-protein interactions. However, aside from peptide-based libraries targeting proteases, 33,[37][38] no DNA or PNA-encoded library specifically designed to engage diverse protein targets in covalent interactions had been reported.…”

Section: Resultsmentioning

confidence: 99%

Screening for covalent inhibitors using DNA-display of small molecule libraries functionalized with cysteine reactive moieties

et al. 2016

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DNA-encoded chemical libraries are increasingly used to identify leads for drug discovery or chemical biology. Despite the resurging interest in covalent inhibitors, libraries are typically designed with synthon filtered out for reactive functionalities that can engage a target through covalent interactions. Herein, we report the synthesis of two libraries containing Michael acceptors to identify cysteine reactive ligands. We developed a simple procedure to discriminate between covalent and high affinity non-covalent inhibitors using DNA display of the library in a microarray format. The methodology was validated with known covalent and high affinity non-covalent kinase inhibitors. Screening of the library revealed novel covalent inhibitors for MEK2 and ERBB2

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“…[26] Synthetic carbohydrates may be an alternative targeting element. [42] However, successful demonstrations of targeted killing of bacteria with glycoconjugates are still limited. [30][31][32][33] The high specificity of carbohydrate-lectin www.advancedsciencenews.com www.advtherap.com Figure 1.…”

Section: Doi: 101002/adtp201900052mentioning

confidence: 99%

Glycosylated Copper Sulfide Nanocrystals for Targeted Photokilling of Bacteria in the Near‐Infrared II Window

Hou

Mahadevegowda

Cuong

et al. 2019

Advanced Therapeutics

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Photothermal and photodynamic therapies are established as alternative approaches to combating bacterial infections; however, the heat and reactive oxygen species generated by the photoagents act on both normal and bacterial cells. A targeting strategy is thus required to minimize side effects and enhance the antibacterial efficiency. Glycoconjugates specifically interacting with bacterial lectins have emerged as a new class of materials for targeting bacteria. In this paper, galactosylated plasmonic copper sulfide nanocrystals (Cu 2−x S NCs) are used to target Pseudomonas aeruginosa via galactose-LecA interactions and kill the bacteria by simultaneous photothermal and photodynamic therapy. Galactosylated Cu 2−x S NCs are obtained by functionalizing the nanocrystals with tri-thiogalactoside glycoclusters. The excellent specificity of galactosylated nanoparticles toward LecA with a LecA-deficient P. aeruginosa strain as the control is first demonstrated. Afterward, a laser in the near-infrared II window is used to kill the bacteria, and the critical role of targeted binding in efficient killing of bacteria is highlighted. This approach can be readily generalized to the targeting of other pathogens which have highly specific carbohydrate-binding lectins.

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A LecA Ligand Identified from a Galactoside‐Conjugate Array Inhibits Host Cell Invasion by Pseudomonas aeruginosa

Cited by 85 publications

References 35 publications

Mannose-centered aromatic galactoclusters inhibit the biofilm formation of Pseudomonas aeruginosa

Mannose-centered aromatic galactoclusters inhibit the biofilm formation of Pseudomonas aeruginosa

Screening for covalent inhibitors using DNA-display of small molecule libraries functionalized with cysteine reactive moieties

Glycosylated Copper Sulfide Nanocrystals for Targeted Photokilling of Bacteria in the Near‐Infrared II Window

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