Researchers have identified a new class of antibiotics with the potential to tackle a drug-resistant bacterium, Acinetobacter baumannii. Zosurabalpin was found to be effective against CRAB (carbapenem-resistant Acinetobacter baumannii)-induced pneumonia and sepsis in mouse models.
Writing in Nature, Zampaloni et al and Pahil et al reported the identification and analysis of the antibiotic zosurabalpin that can kill Acinetobacter baumannii, antibiotic-resistant strains of which are hard to treat in the clinic. Dr. Zampaloni and colleagues identified a tethered macrocyclic peptide (MCP) that selectively kills A. baumannii. The compound was further optimised for efficacy and tolerability, and the fine-tuning culminated in zosurabalpin, a drug candidate.
In an article, Morgan K. Gugger and Paul J. Hergenrother, Department of Chemistry, University of Illinois at Urbana-Champaign wrote that copious evidence provided by Zampaloni et al indicates that the antibiotic kills A. baumannii through a previously unknown mode of action. It inhibits a key process, transport of the molecule lipopolysaccharide (LPS), by inhibiting a complex of proteins. This complex was essential for transporting LPS to the bacterial surface to create the outer-membrane structure of Gram-negative bacteria. Zosurabalpin blocks LPS transport, and the abnormal build-up of LPS in the cell kills the bacterium.
“It was effective against more than 100 CRAB clinical samples tested in the laboratory and it considerably reduced the levels of bacteria in mice with CRAB-induced pneumonia and prevented the death of mice with a CRAB-induced abnormal immune response called sepsis,” the article said. The antibiotic has been evaluated in two phase I clinical trials.
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