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Article

Global Transcriptional Response of Methylorubrum extorquens to Formaldehyde Stress Expands the Role of EfgA and Is Distinct from Antibiotic Translational Inhibition

1
Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA
2
Institute for Modeling Collaboration and Innovation, University of Idaho, Moscow, ID 83844, USA
3
Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID 83844, USA
4
Department of Plant and Microbial Biology, University of Minnesota, Twin Cities, MN 55108, USA
5
Microbial and Plant Genomics Institute, University of Minnesota, Twin Cities, MN 55108, USA
6
Biotechnology Institute, University of Minnesota, Twin Cities, MN 55108, USA
7
Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
*
Author to whom correspondence should be addressed.
Authors contributed equally to the work.
Academic Editor: Emilie Muller
Microorganisms 2021, 9(2), 347; https://doi.org/10.3390/microorganisms9020347
Received: 9 January 2021 / Revised: 7 February 2021 / Accepted: 8 February 2021 / Published: 10 February 2021
(This article belongs to the Special Issue Microbial One-Carbon Metabolism of Natural and Engineered Systems)
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. View Full-Text
Keywords: formaldehyde; stress response; translation inhibition; kanamycin; methylotrophy; enhanced formaldehyde growth EfgA; EfgB; proteotoxicity formaldehyde; stress response; translation inhibition; kanamycin; methylotrophy; enhanced formaldehyde growth EfgA; EfgB; proteotoxicity
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MDPI and ACS Style

Bazurto, J.V.; Riazi, S.; D’Alton, S.; Deatherage, D.E.; Bruger, E.L.; Barrick, J.E.; Marx, C.J. Global Transcriptional Response of Methylorubrum extorquens to Formaldehyde Stress Expands the Role of EfgA and Is Distinct from Antibiotic Translational Inhibition. Microorganisms 2021, 9, 347. https://doi.org/10.3390/microorganisms9020347

AMA Style

Bazurto JV, Riazi S, D’Alton S, Deatherage DE, Bruger EL, Barrick JE, Marx CJ. Global Transcriptional Response of Methylorubrum extorquens to Formaldehyde Stress Expands the Role of EfgA and Is Distinct from Antibiotic Translational Inhibition. Microorganisms. 2021; 9(2):347. https://doi.org/10.3390/microorganisms9020347

Chicago/Turabian Style

Bazurto, Jannell V.; Riazi, Siavash; D’Alton, Simon; Deatherage, Daniel E.; Bruger, Eric L.; Barrick, Jeffrey E.; Marx, Christopher J. 2021. "Global Transcriptional Response of Methylorubrum extorquens to Formaldehyde Stress Expands the Role of EfgA and Is Distinct from Antibiotic Translational Inhibition" Microorganisms 9, no. 2: 347. https://doi.org/10.3390/microorganisms9020347

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