Researchers applied a new technology to generate the full inventory of mutations in the bacterial species Escherichia coli where the antibiotic rifampicin attaches to and disables an essential bacterial enzyme known as RNA polymerase (RNAP).
Modern medicine depends on antibiotics to treat infections by disabling targets inside bacterial cells. Once inside these cells, antibiotics bind to certain sites on specific enzyme targets to stop bacterial growth. Randomly occurring changes in the genes for these targets occur naturally, in some cases making the target harder for the antibiotic to attach to, and that bacterial version resistant to treatment.
For this reason, the more antibiotics have been used over time, the greater the chances that bacterial populations will evolve to have mutants resistant to existing antibiotics, and the more urgent the call for new approaches to keep the treatments from becoming obsolete. Researchers have for decades studied resistant mutants in hopes that related mechanisms would guide the design of new treatments to overcome resistance.
To address this challenge, a new study led by researchers at NYU Grossman School of Medicine applied a technology called MAGE to generate the full inventory of mutations in the bacterial specieswhere the antibiotic rifampicin attaches to and disables an essential bacterial enzyme known as RNA polymerase .
"These techniques could be applied to map the binding sites of other drug types, and especially to those vulnerable to resistance," says co-senior study investigator, Aviram Rasouly, PhD, a research scientist at NYU Langone. Funding support for the study was provided through National Institute of Health grants T32 AI007180 and R01GM126891 and the Blavatnik Family Foundation. The study was led by MD-PhD student Kevin Yang. Other NYU Langone researchers involved in this study were Maria Cameranesi, Criseyda Martinez, Manjunath Gowder, Yosef Shamovsky, Vitaliy Epshtein, Khaled Alzoubi, Zhitai Hao, and Ilya Shamovsky. Evgeny Nudler is also an investigator with the Howard Hughes Medical Institute.
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