2-Deoxy-d-glucose is a potent inhibitor of biofilm growth in Escherichia coli

Abstract

Escherichia coli strain 15 (ATCC 9723), which forms robust biofilms, was grown under optimal biofilm conditions in NaCl-free Luria-Bertani broth (LB*) or in LB* supplemented with one of the non-metabolizable analogues 2-deoxy-D-glucose (2DG), methyl a-D-mannopyranoside (aMM), or methyl a-D-glucopyranoside (aMG). Biofilm growth was inhibited by mannose analogue 2DG even at very low concentration in unbuffered medium, and the maximal inhibition was enhanced in the presence of either 100 mM KPO 4 or 100 mM MOPS, pH 7.5; in buffered medium, concentrations of 0.02 % (1.2 mM) or more inhibited growth nearly completely. In contrast, mannose analogue aMM, which should not be able to enter the cells but has been reported to inhibit biofilm growth by binding to FimH, did not exhibit strong inhibition even at concentrations up to 1.8 % (108 mM). The glucose analogue aMG inhibited biofilm growth, but much less strongly than did 2DG. None of the analogues inhibited planktonic growth or caused a change in pH of the unbuffered medium. Similar inhibitory effects of the analogues were observed in minimal medium. The effects were not strain-specific, as 2DG and aMG also inhibited the weak biofilm growth of E. coli K12.

Termination of Poly-N-acetylglucosamine (PNAG) Polymerization with N-Acetylglucosamine Analogues

“…The incorporation of modified bacterial sugars, such as 3-deoxy- d -manno-octulosonic acid (KDO), pseudaminic acid, legionaminic acid, and trehalose, which are salvaged and presented by bacteria in specific glycans, have provided innovative bacterial imaging methods . Feeding of deoxy and fluorosugars has been shown to modify the growth and biofilm phenotypes of bacteria. − Similarly, other modified monosaccharides are taken up and incorporated into glycans in a species-specific manner, stimulating research into the metabolic pathways and structures that are produced. − Engineering of bacteria to introduce novel monosaccharide salvage pathways has led to the production of tagged fucosylated O-antigens and modified peptidoglycan structures. − Recently, the metabolic engineering of bacteria combined with a modified muramic acid residue has demonstrated the potential of monosaccharide tools in monitoring peptidoglycan biosynthesis in H. pylori . Here, we demonstrate that metabolic engineering of the E. coli GlcNAc salvage pathway and the use of GlcNAc derivatives provides a method to control the synthesis of poly- N -acetylglucoasamine (PNAG), a key bacterial exopolysaccharide in biofilm formation …”

CO2 enhances the formation, nutrient scavenging and drug resistance properties of C. albicans biofilms

“…Encouragingly, 2-DG was able to attenuate C. albicans biofilm growth in both 5% and atmospheric (0.03%) CO 2 environments. 2-DG has exhibited antimicrobial effects against fungal moulds 58 and bacterial biofilms 59 . This, together with its action against C. albicans biofilms presented here, highlights the potential for 2-DG to be used an anti-biofilm therapeutic.…”

CO2enhances the ability ofCandida albicansto form biofilms, overcome nutritional immunity and resist antifungal treatment

“…Encouragingly, 2-deoxyglucose (2-DG) was able to attenuate C. albicans biofilm growth in both 5% and atmospheric (0.03%) CO 2 environments. 2-DG has exhibited antimicrobial effects against fungal moulds 75 and bacterial biofilms 76 . This, together with its action against C. albicans biofilms presented here, highlights the potential for 2-DG to be used an anti-biofilm therapeutic.…”