EfgA is a conserved formaldehyde sensor that leads to bacterial growth arrest in response to elevated formaldehyde
| Autor: | Jessica A. Lee, Tomislav Ticak, Chandler N. Hellenbrand, Dipti D. Nayak, F. Marty Ytreberg, Jannell V. Bazurto, Jagdish Suresh Patel, Milya Davlieva, Leah B. Lambert, Christopher J. Marx, Jill L. Johnson, Olivia J. Benski, Yousif Shamoo, Caleb J. Quates |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Formates Enzyme Metabolism Bacterial growth medicine.disease_cause Biochemistry chemistry.chemical_compound Biology (General) Enzyme Chemistry Data Management Cellular Stress Responses chemistry.chemical_classification Crystallography biology Organic Compounds Physics General Neuroscience Monomers Phylogenetic Analysis Condensed Matter Physics Phylogenetics Chemistry Methylobacterium Cell Processes Physical Sciences Crystal Structure General Agricultural and Biological Sciences Research Article Computer and Information Sciences QH301-705.5 030106 microbiology Formaldehyde General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Stress Physiological Methylobacterium extorquens medicine Solid State Physics Evolutionary Systematics Escherichia coli Taxonomy Evolutionary Biology Aldehydes Bacteria General Immunology and Microbiology Toxin Organic Chemistry Chemical Compounds Biology and Life Sciences Cell Biology Metabolism Polymer Chemistry biology.organism_classification 030104 developmental biology Enzyme chemistry Enzymology Heterologous expression |
| Zdroj: | PLoS Biology PLoS Biology, Vol 19, Iss 5, p e3001208 (2021) |
| ISSN: | 1545-7885 |
| Popis: | Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here, we identify a member of the DUF336 domain family, named efgA for enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response in M. extorquens PA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that rapidly arrests growth in response to elevated levels of formaldehyde. Heterologous expression of EfgA in Escherichia coli increases formaldehyde resistance, indicating that its interaction partners are widespread and conserved. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and safeguards cells from potential damage. The known formaldehyde stress response systems involve enzymatic detoxification. Here, the authors show that the formaldehyde sensor efgA plays an important role in the endogenous formaldehyde stress response in Methylorubrum extorquens, halting cell growth in response to elevated levels of formaldehyde, and is found almost exclusively in methylotrophic taxa. |
| Databáze: | OpenAIRE |
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