Carbohydrate-Based Antibiotics: A New Approach to Tackling the Problem of Resistance

Abstract

Recent interest in the problem of antibiotic resistance has led to the identification of new targets and strategies for antibiotic discovery. Among these efforts, the development of small molecules as antibiotics to target carbohydrate receptors or carbohydrate‐modifying enzymes represents a new direction. This review covers recent work in this regard and discusses the impact of each strategy on the development of drug resistance. Particularly interesting targets include unique cell‐surface carbohydrates, the transglycosylase involved in peptidoglycan biosynthesis, and bacterial RNA. With a greater understanding of the genome of different bacteria as well as advances in functional genomics and proteomics, we can expect the discovery of a variety of targets for the development of novel antibiotics.

Crystal structure of Staphylococcus aureus transglycosylase in complex with a lipid II analog and elucidation of peptidoglycan synthesis mechanism

“…Multiple sequence alignment analyses reveal that five motifs of TG in various methicillin-resistant S. aureus and drug-resistant Gram-negative bacteria (e.g., Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Mycobacterium tuberculosis are highly conserved (SI Appendix, Fig. S1), and the polysaccharide backbone of the peptidoglycan always remains unchanged in WT and resistant strains (7). Thus, new antibiotics that target the transglycosylation step may be less prone to resistance development.…”

Novel drug delivery systems to combat antimicrobial resistance

“…In fact new molecules that mimic critical carbohydrates with improved properties could be a promising approach [92]. Targeting the inhibition of lipopolysaccharide (LPS), specifically the synthesis of the lipid A region, in gram-negative bacteria is such an approach.…”

Synthesis, Characterization and Physicochemical Analysis of some Mannofuranoside Derivatives with Potent Antimicrobial Activity

“…The potential of sugars as starting compounds for highly efficient syntheses of carbohydrate conjugates are now well recognized with regard to antibacterial, antiviral, antineoplastic, antiprotozoal and antifungal activity [3][4][5][6][7][8][9] . Heterocyclic chemistry has wide array of biologically active compounds isolated from natural sources or synthesized in the laboratory, such as coumarins [10][11][12] , quinolines 13,14 , triazoles 15 and phenolics 16,17 etc.…”