Amazing stuff! Wonders of life! Towards more powerful antibiotics!
"Researchers have discovered a new stress signaling system that enables bacteria cells to adapt and protect themselves against the immune system and certain antibiotics.
An enzyme, RlmN, was observed to directly sense chemical and environmental stresses, and rapidly signal for the production of other proteins that allow the bacteria cell to adapt and survive. This breakthrough discovery of RlmN as a stress sensor has revealed a new mechanism of antimicrobial resistance that can be targeted for drug development. ...
The work was carried out by researchers from the ... interdisciplinary research group at the Singapore-MIT Alliance for Research and Technology (SMART), ... in collaboration with MIT, the Singapore Center for Environmental Life Sciences Engineering, and Nanyang Technological University Singapore. ...
The discovery was made using a sophisticated mass spectrometry technology developed at SMART and MIT to simultaneously identify all 50 different ribonucleic acids (RNA) modifications in bacteria. This approach allowed scientists to observe changes in cell behavior or pattern mutations that cannot be detected when studied individually. ..."
From the abstract:
"Bacteria possess elaborate systems to manage reactive oxygen and nitrogen species (ROS) arising from exposure to the mammalian immune system and environmental stresses. Here we report the discovery of an ROS-sensing RNA-modifying enzyme that regulates translation of stress-response proteins in the gut commensal and opportunistic pathogen Enterococcus faecalis. We analyze the tRNA epitranscriptome of E. faecalis in response to reactive oxygen species (ROS) or sublethal doses of ROS-inducing antibiotics and identify large decreases in N2-methyladenosine (m2A) in both 23 S ribosomal RNA and transfer RNA. This we determine to be due to ROS-mediated inactivation of the Fe-S cluster-containing methyltransferase, RlmN. Genetic knockout of RlmN gives rise to a proteome that mimics the oxidative stress response, with an increase in levels of superoxide dismutase and decrease in virulence proteins. While tRNA modifications were established to be dynamic for fine-tuning translation, here we report the discovery of a dynamically regulated, environmentally responsive rRNA modification. These studies lead to a model in which RlmN serves as a redox-sensitive molecular switch, directly relaying oxidative stress to modulating translation through the rRNA and the tRNA epitranscriptome, adding a different paradigm in which RNA modifications can directly regulate the proteome."
An RNA modification enzyme directly senses reactive oxygen species for translational regulation in Enterococcus faecalis (open access)
Fig. 6: Working model of RlmN as a sensor for oxidative stress
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