Hidden genes may be tapped for new antibiotics

Silents are potentially golden in the search for antibiotics to slow the ongoing crisis of resistance in the treatment of disease.

Rice University bioscientists have designed novel on and off switches to control the “silent” genes in a strain of bacteria. Their strategy could boost the perpetual search for new antibiotics.

The researchers customized CRISPR tools to control the expression of genes in Streptomyces bacteria that, in nature, are only expressed when necessary. Until now, those genes have been challenging for synthetic biologists to access.

“As labs started to sequence the genomes of these organisms that were known to produce one or a few antibiotics, we realized that the pathways responsible for the production of antibiotic and other molecules of interest are much more abundant than previously thought,” said James Chappell, an assistant professor of biosciences whose lab studies bacteria and ways to engineer them.

“Each Streptomyces strain is now predicted to be able to produce up to 40 different molecules of interest, including antibiotics, on average,” he said.

The work led by Chappell and graduate student Andrea Ameruoso may allow labs to quickly develop libraries of possible antibiotics to test on pathogens. Significantly, they said that while CRISPR-Cas9 has been used to create a platform to activate genes in organisms like Escherichia coli, this is the first time it’s been applied to Streptomyces.

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