An as yet undiscovered treasury of desired drug-like molecules is hidden in the genomes of living things. Streptomyces Bacteria responsible for the first bacterial antibiotics to treat tuberculosis in the 1940s.
But isolating them has proven difficult. Now, St. Biologists at the University of Washington in St. Louis are using comparative metabologenomics to uncover what might be “silencing.” Streptomyces and preventing it from producing the desired compounds encoded by its genes.
“We studied genetic differences between the genomes of young people. Streptomyces When looking at antibiotic outputs at the same time,” says Joshua Blodgett, an assistant professor in the Department of Biology for Arts and Sciences, who is the corresponding author of the study published in the journal Science. Proceedings of the National Academy of Sciences (PNAS). “This study highlights comparative metabologenomics as a powerful approach to uncover traits that distinguish strong antibiotic producers from weak ones.”
Blodgett’s team, the final Ph.D. MA Yunci Qi and postdoctoral research fellow Keshav Nepal compared a group of antibiotic-producing strains. Streptomyces and other non-productive or poorly producing strains to reveal genomic differences that may affect drug production.
The researchers found several key differences between the strains. In particular, good manufacturers of polycyclic tetramate macrolactam (PTM) antibiotics seemed to take advantage of the production of griseorhodin, which the researchers did not foresee and initially tried to eliminate.
But a handful of nucleotides are also important. Metabologenomics revealed that the presence or absence of two to three nucleotides (mainly letters that make up a genetic message) can set the switches that drive PTM antibiotic production. This kind of precise control has previously been found in some disease-causing bacteria, but has been largely overlooked in drug-producing bacteria.
“Our work highlights the problem of silent gene clusters and the need to understand them for next-generation drug discovery,” said Blodgett. Said. “Comparative metabologenomics is a generally acceptable strategy, and we hope others can use it to study their own strains and drug pathways.”
New insights into antibiotic production by bacteria
Yunci Qi et al, A comparative metabologenomic approach reveals mechanistic insights into Streptomyces antibiotic cryptography, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2103515118
Provided by the University of Washington in St. Louis.
Quotation: Distinguishing strong antibiotic manufacturers from weak ones (2021, 30 July), retrieved July 30, 2021 from https://phys.org/news/2021-07- Differentiating-strong-antibiotic-weaker.html.
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