RT Journal Article
SR Electronic
T1 EfgA is a conserved formaldehyde sensor that halts bacterial translation in response to elevated formaldehyde
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.16.343392
DO 10.1101/2020.10.16.343392
A1 Jannell V. Bazurto
A1 Dipti D. Nayak
A1 Tomislav Ticak
A1 Milya Davlieva
A1 Jessica A. Lee
A1 Leah B. Lambert
A1 Olivia J. Benski
A1 Caleb J. Quates
A1 Jill L. Johnson
A1 Jagdish Suresh Patel
A1 F. Marty Ytreberg
A1 Yousif Shamoo
A1 Christopher J. Marx
YR 2020
UL http://biorxiv.org/content/early/2020/10/17/2020.10.16.343392.abstract
AB 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 inhibits translation 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 and may include translational machinery. 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 modulates translational activity.Competing Interest StatementThe authors have declared no competing interest.