The potency and indiscriminate nature of formaldehyde reactivity upon biological molecules make it a universal stressor. However, some organisms such as Methylorubrum extorquens possess means to rapidly and effectively mitigate formaldehyde-induced damage. EfgA is a recently identified formaldehyde sensor predicted to halt translation in response to elevated formaldehyde as a means to protect cells. Herein, we investigate growth and changes in gene expression to understand how M. extorquens responds to formaldehyde with and without the EfgA-formaldehyde-mediated translational response, and how this mechanism compares to antibiotic-mediated translation inhibition. These distinct mechanisms of translation inhibition have notable differences: they each involve different specific players and in addition, formaldehyde also acts as a general, multi-target stressor and a potential carbon source. We present findings demonstrating that in addition to its characterized impact on translation, functional EfgA allows for a rapid and robust transcriptional response to formaldehyde and that removal of EfgA leads to heightened proteotoxic and genotoxic stress in the presence of increased formaldehyde levels. We also found that many downstream consequences of translation inhibition were shared by EfgA-formaldehyde-and kanamycin-mediated translation inhibition. Our work uncovered additional layers of regulatory control enacted by functional EfgA upon experiencing formaldehyde stress, and further demonstrated the importance this protein plays at both transcriptional and translational levels in this model methylotroph.
|Original language||English (US)|
|Number of pages||22|
|State||Published - Feb 2021|
Bibliographical noteFunding Information:
Funding: Christopher J. Marx and Jeffrey E. Barrick were supported by funding from the Army Research Office grant W911NF-12-1-0390. Siavash Riazi was supported by fellowships from the Bi-oinformatics and Computational Biology Graduate Program and the Department of Biological Sciences. Support was also received via pilot grants to Jannell V. Bazurto from the BEACON Center for Evolution in Action (parent award DBI-0939454) and Christopher J. Marx from the Institute for Modelling Collaboration and Innovation (parent award P20GM104420).
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Enhanced formaldehyde growth EfgA
- Stress response
- Translation inhibition