Tuesday 7 September 2021

Differentiating strong antibiotic producers from weaker ones


An untapped trove of desirable drug-like molecules is hidden in the genomes of Streptomyces bacteria -- the same bacteria responsible for the first bacterial antibiotics to treat tuberculosis back in the 1940s.


Isolating them, however, has proved challenging. Now, biologists are using comparative metabologenomics to try to uncover what may be "silencing" Streptomyces and preventing it from producing desirable compounds encoded by its genes.


Researchers compared a group of antibiotic-producing strains of Streptomyces and other nonproducing or poor-producing strains to reveal genomic differences that could affect drug production.



The researchers found a few key differences between the strains. Notably, the good producers of polycyclic tetramate macrolactam (PTM) antibiotics seemed to benefit from griseorhodin production, which the researchers did not anticipate and originally had tried to eliminate.


But a handful of nucleotides matter, too. Metabologenomics revealed that the presence or absence of two to three nucleotides -- essentially letters that make up a genetic message -- can tune the switches that drive PTM antibiotic production. This type of fine control previously had been found in certain bacteria that cause disease, but largely had been overlooked in bacteria that produce drugs.




Yunci Qi, Keshav K. Nepal, Joshua A. V. Blodgett. A comparative metabologenomic approach reveals mechanistic insights into Streptomyces antibiotic crypticity. Proceedings of the National Academy of Sciences, 2021; 118 (31): e2103515118 DOI: 10.1073/pnas.2103515118


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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