Tuesday, July 26, 2022

There’s now a better way to create clinical-grade bacteriophages that kill antibiotic-resistant bacteria

Good news! This could be a breakthrough!

"... Now, a team of researchers based in Germany offers a potentially faster and better way to create these bacteriophages, or simply phages. Their method, which they dub a “phactory,” produces phages without having to culture the bacteria they are directed against, and allows tweaking of the viruses to tailor them to specific antibiotic-resistant infections. ...
In the new report, they show these E. coli extracts can produce viruses directed against other harmful bacteria, such as those that cause pneumonia or plague, if given the right phage DNA. ...
Another advantage of the team’s approach is the ability to engineer the assembled phages and study the results in detail. They don’t do this by changing the phage genome itself, but by adding to the soup DNA loops called plasmids that are independently translated to create modified phage proteins. These proteins are incorporated into the new viruses—but not into their progeny. ..."

From the abstract:
"Bacteriophages are potent therapeutics against biohazardous bacteria, which rapidly develop multidrug resistance. However, routine administration of phage therapy is hampered by a lack of rapid production, safe bioengineering, and detailed characterization of phages. Thus, we demonstrate a comprehensive cell-free platform for personalized production, transient engineering, and proteomic characterization of a broad spectrum of phages. Using mass spectrometry, we validated hypothetical and non-structural proteins and could also monitor the protein expression during phage assembly. Notably, a few microliters of a one-pot reaction produced effective doses of phages against enteroaggregative Escherichia coli (EAEC), Yersinia pestis, and Klebsiella pneumoniae. By co-expressing suitable host factors, we could extend the range of cell-free production to phages targeting gram-positive bacteria. We further introduce a non-genomic phage engineering method, which adds functionalities for only one replication cycle. In summary, we expect this cell-free methodology to foster reverse and forward phage engineering and customized production of clinical-grade bacteriophages."

There’s now a cleaner, better way to create viruses that kill antibiotic-resistant bacteria | Science | AAAS New method to make phages could help jump-start clinical trials





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