Synthesis of bioinspired carbohydrate amphiphiles that promote and inhibit biofilms

Dane, Eric L.; Ballok, Alicia E.; O’Toole, George A.; Grinstaff, Mark W.

doi:10.1039/c3sc52777h

Cited by 55 publications

(56 citation statements)

References 45 publications

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“…Indeed, rarely have sugar-based inhibitors of E. coli-generated biofilms been reported although a number have for biofilms mediated by Pseudomonas aeruginosa. 70,71 The fact that Man 3 N 3 does not feature any triazole segment in the vicinity of the sugar moiety strongly suggests that the presence of the heterocycle as an integral feature of the 1 st -generation NDs is not critical for their ability to inhibit biofilm formation. In addition, neither the ND-OH nor ND-Lac 3 controls are seen to show any anti-adhesive activity, underlining that the activities observed for the thiomannosyl conjugates are sugar-specific.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of type 1 fimbriae-mediated Escherichia coli adhesion and biofilm formation by trimeric cluster thiomannosides conjugated to diamond nanoparticles

et al. 2015

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Inhibition of type 1 fi mbriae-mediated Escherichia coli adhesion and biofi lm formation by trimeric cluster thiomannosides conjugated to diamond nanoparticles Trimeric thiosugar clusters, conveniently obtained through a thiol-ene "click" strategy, have been effi ciently conjugated to alkynyl-functionalized nanodiamonds (NDs) using a Cu(I)-catalysed "click" reaction. These tri-thiomannoside clusterconjugated NDs (ND-Man 3 ) are shown to be potent inhibitors of type 1 fi mbriae-mediated E. coli adhesion to yeast and T24 bladder cells and moreover to inhibit E. coli-mediated biofi lm formation. This latter feature has only rarely been reported in the past for analogues featuring such simple multivalent glycosidic motifs and would constitute a useful additional characteristic of any anti-adhesive drug lead. anti-adhesive nanoparticles displaying activity against biofilms. In this work, trimeric thiomannoside clusters conjugated to nanodiamond particles (ND) were targeted for investigation. NDs have attracted attention as a biocompatible nanomaterial and we were curious to see whether the high mannose glycotope density obtained upon grouping monosaccharide units in triads might lead to the corresponding NDconjugates behaving as effective inhibitors of E. coli type 1 fimbriae-mediated adhesion as well as of biofilm formation. The required trimeric thiosugar clusters were obtained through a convenient thiol-ene "click" strategy and were subsequently conjugated to alkynyl-functionalized NDs using a Cu(I)-catalysed "click" reaction. We demonstrated that the tri-thiomannoside cluster-conjugated NDs (ND-Man 3 ) show potent inhibition of type 1 fimbriae-mediated E. coli adhesion to yeast and T24 bladder cells as well as of biofilm formation. The biofilm disrupting effects demonstrated here have only rarely been reported in the past for analogues featuring such simple glycosidic motifs. Moreover, the finding that the tri-thiomannoside cluster (Man 3 N 3 ) is itself a relatively efficient inhibitor, even when not conjugated to any ND edifice, suggests that alternative mono-or multivalent sugar-derived analogues might also be usefully explored for E. coli-mediated biofilm disrupting properties.

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Section: Discussionmentioning

confidence: 99%

Inhibition of type 1 fimbriae-mediated Escherichia coli adhesion and biofilm formation by trimeric cluster thiomannosides conjugated to diamond nanoparticles

et al. 2015

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“…Future work will focus on the development of analogues with decreased toxicity toward mammalian cells. (12) 100 50…”

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confidence: 99%

Biofilm‐Eradicating Properties of Quaternary Ammonium Amphiphiles: Simple Mimics of Antimicrobial Peptides

et al. 2014

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Bacterial biofilms are difficult to eradicate because of reduced antibiotic sensitivity and altered metabolic processes; thus, the development of new approaches to biofilm eradication is urgently needed. Antimicrobial peptides (AMPs) and quaternary ammonium cations (QACs) are distinct, yet well-known, classes of antibacterial compounds. By mapping the general regions of charge and hydrophobicity of QACs onto AMP structures, we designed a small library of QACs to serve as simple AMP mimics. In order to explore the role that cationic charge plays in biofilm eradication, structures were varied with respect to cationic character, distribution of charge, and alkyl side chain. The reported compounds possess minimum biofilm eradication concentrations (MBEC) as low as 25 μM against Gram-positive biofilms, making them the most active anti-biofilm structures reported to date. These potent AMP mimics were synthesized in 1-2 steps and hint at the minimal structural requirements for biofilm destruction.

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“…Natural Nucleic acids [66] Carbohydrates [67] Lipids [68] Small molecules [54] Synthetic Carbohydrate, nucleic acid and small molecule analogues [54,69] …”

Section: Nonproteinaceous Antibiofilm Agentsmentioning

confidence: 99%

Development of Broad-Spectrum Antibiofilm Drugs: Strategies and Challenges

et al. 2015

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The severity of many chronic bacterial infections is mainly due to the biofilm mode of life adapted by pathogenic bacteria. The bacteria in biofilm-stage exhibit high resistance to host immune responses and antimicrobials, which complicates the treatment process and results in life threatening conditions. Most of the chronic infections are polymicrobial in nature. In order to combat the polymicrobial biofilm infections and to increase the efficiency of antimicrobials, there is an urgent need for broad-spectrum antibiofilm drugs. This review discusses the clinical needs and current status of broad-spectrum antibiofilm drugs with special emphasis on prospective strategies and hurdles in the process of new drug discovery.

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Synthesis of bioinspired carbohydrate amphiphiles that promote and inhibit biofilms

Cited by 55 publications

References 45 publications

Inhibition of type 1 fimbriae-mediated Escherichia coli adhesion and biofilm formation by trimeric cluster thiomannosides conjugated to diamond nanoparticles

Inhibition of type 1 fimbriae-mediated Escherichia coli adhesion and biofilm formation by trimeric cluster thiomannosides conjugated to diamond nanoparticles

Biofilm‐Eradicating Properties of Quaternary Ammonium Amphiphiles: Simple Mimics of Antimicrobial Peptides

Development of Broad-Spectrum Antibiofilm Drugs: Strategies and Challenges

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