The British journal Nature recently published a new microbiological discovery: scientists report that natural products such as arylomycin can be chemically optimized to be highly effective against multi-drug resistant Gram-negative bacteria such as E. coli. A broad spectrum antibacterial activity compound. The latest research in this in vitro and mouse experiment can make these compounds a new and essential drug to counter a serious threat to global health.
Multi-drug resistant bacteria are increasing. At present, the "super bacteria" encountered in clinical practice generally refers to ESKAPE, which represents six famous resistant bacteria. Among them, Gram-negative bacteria (such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii) are particularly threatened - their double outer membrane makes many antibiotics inaccessible to the target. point. Although researchers have made a lot of efforts, over the past 50 years, there have been no new antibiotics with antibacterial activity against Gram-negative bacteria.
Arylomycin is a class of macrocyclic lipopeptides that inhibit type I signal peptidase (SPase), a key membrane-bound enzyme that breaks down proteins and peptides. In Gram-negative bacteria, the active site of SPase is located between the bacterial cell membrane and the bacterial outer membrane. Researchers have thought that arylomycin could not reach this active site because arylomycin could not penetrate the bacterial outer membrane.
The research team of the American Genetic Engineering Technology Corporation (Genentech) discovered an arylomycin-like synthesis called G0775 in the process of finding arylomycin derivatives with better target affinity and stronger outer membrane penetration. The derivative has strong in vitro antibacterial activity against ESKAPE pathogens and can penetrate the bacterial outer membrane through an atypical mechanism.
The researchers found that super multidrug-resistant strains resistant to almost all known antibiotics are still sensitive to G0775 and have a lower incidence of drug resistance. The antibacterial efficacy of G0775 against Gram-negative pathogens was confirmed in multiple infected mouse models.
Fufeng Sinuote Biotechnology Co.,Ltd. , https://www.sntbiology.com