Key result
A lipid-conjugated methyl sulfone analog of glutamyl-adenosine significantly reduced GatCAB's transamination rate and exhibited antibacterial activity in live bacteria.
Its licence doesn't allow us to show a copy here.
Why the study?
GatCAB is an antibacterial drug target, but previously identified in vitro inhibitors had not shown potent activity against live bacteria.
Lipid-conjugated methyl sulfone analogs of glutamyl-adenosine show promise as novel antibacterial agents by inhibiting GatCAB and demonstrating cell permeability in live bacteria.
No immediate impact on H. pylori therapy; leaves open whether GatCAB inhibition can yield live-bacterial activity.
amidotransferase (GatCAB) has been proposed as a novel antibacterial drug target due to its indispensability in prominent human pathogens. While several inhibitors with in vitro activity have been identified, none have been demonstrated to have potent activity against live bacteria. In this work, seven non-hydrolyzable transition state mimics of GatCAB were synthesized and tested as the transamidase inhibitors against GatCAB from the human pathogen Helicobacter pylori. Notably, the methyl sulfone analog of glutamyl-adenosine significantly reduced GatCAB's transamination rate. Additionally, four lipid-conjugates of these mimics displayed antibacterial activity against Bacillus subtilis, likely due to enhanced cell permeability. Inhibitory activity against GatCAB in live bacteria was confirmed using a sensitive gain-of-function dual luciferase reporter in Mycobacterium bovis-BCG. Only the lipid-conjugated methyl sulfone analog exhibited a significant increase in mistranslation rate, highlighting its cell permeability and inhibitory potential. This study provides insights for developing urgently needed novel antibacterial agents amidst emerging antimicrobial drug resistance.
No takes yet. Share an insight, caveat, or question.
Sangsuwan et al. (2024) studied Bacterial infection. Synthetic analogs of aminoacyl-adenosine was evaluated on GatCAB transamination rate and mistranslation rate. A lipid-conjugated methyl sulfone analog of glutamyl-adenosine significantly reduced GatCAB's transamination rate and exhibited antibacterial activity in live bacteria.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: