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Published on: January 7, 2022
Peptidoglycan-Directed Chemical Ligation for Selective Inhibition on Gram-Positive Bacteria
Feng Jiang1, Chengteng Cai1, Lei Gao1
1Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, State Key Laboratory of Cellular Stress Biology, the Key Laboratory for Chemical Biology of Fujian Province, and the MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen 361005, China.
Abstract:
Microbicides with distinct antibacterial mechanisms show potential to combat multi-drug resistance bacteria. We herein report peptidoglycan-directed chemical ligation (PGCL) between alkyne-bearing vancomycin and an azide-tagged cationic polymer. The former binds peptidoglycan and inhibits peptidoglycan crosslinking, while the latter interferes the integrity of the bacterial membrane. PGCL results in enhanced bactericidal activity against Gram-positive Staphylococcus aureus (S. aureus) over Gram-negative Escherichia coli (E. coli). These data indicate the potential of PGCL to selectively and synergistically inhibit Gram-positive pathogens via dual modality antibacterial mechanisms of peptidoglycan-inhibiting antibiotics and bacterial membrane-disrupting polycations.
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