New antibiotics could eventually fight superbugs

上一篇 / 下一篇  2018-09-17 14:47:38 / 個人分類:健康

Natural products such as arylomycin are chemically optimized to become potent, broad-spectrum antibacterial compounds against multidrug-resistant gram-negative bacteria, such as e. coli, scientists report. The latest findings, in vitro and in mice, could allow the compound to become a new essential drug to combat a serious threat to global health.

Multidrug-resistant bacteria are on the rise. Currently, "superbugs" commonly refer to ESKAPE, and the six letters represent six well-known drug-resistant bacteria. The threat is particularly acute with gram-negative bacteria (e. coli, klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter baumannii), whose double membranes keep many antibiotics from reaching their targets. Despite the efforts of researchers, no new antibiotic has been developed for gram-negative bacteria for more than 50 years.

Arylomycin type is a kind of can restrain Ⅰ signal peptide enzyme (SPase) fat macrocyclic peptides, type and Ⅰ signal peptide enzyme can decompose protein and polypeptide a membrane combination of key enzyme. In gram-negative bacteria, the active site of SPase lies between the bacterial cell membrane and the bacterial outer membrane. Researchers had thought that arylomycin could not reach the active site because it could not penetrate the bacteria's outer membrane.

Gene engineering technology companies in the United States (genentech) research team, the searching for targets of outer membrane penetration is better, stronger affinity arylomycin derivatives were in the process, found a called G0775 arylomycin synthetic derivatives, has strong antibacterial activity in vitro of ESKAPE pathogenic bacteria, and can through a kind of typical mechanism through bacterial outer membrane.

The researchers found that hyperresistant bacteria that are resistant to almost all known antibiotics remain sensitive to G0775 and have a low incidence of resistance. The antibacterial efficacy of G0775 against gram-negative pathogens was demonstrated in multiple infected mouse models.






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