Abstract
Glyphosate, the most widely used herbicide in both agricultural and urban areas is toxic for plants and for many bacterial species. The mechanism of action of glyphosate is through the inhibition of the EPSP synthase, a key enzyme in the biosynthetic pathway of aromatic amino acids. Here we show that glyphosate induces the stringent response in Escherichia coli. Bacteria treated with glyphosate stop growing and accumulate ppGpp. Both growth arrest and ppGpp accumulation are restored to normal levels upon addition of aromatic amino acids. Glyphosate-induced ppGpp accumulation is dependent on the presence of the (p)ppGpp synthetase RelA. However, unlike other cases of amino acid starvation, pppGpp could not be discerned. In a gppA background both ppGpp and pppGpp accumulated when exposed to glyphosate. Conversely, the wild-type strain and gppA mutant treated with serine hydroxamate accumulated high levels of both ppGpp and pppGpp. Altogether, the data indicate that glyphosate induces amino acid starvation resulting in a moderate accumulation of ppGpp and a reversible stringent response.
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Acknowledgements
We thank Michael Cashel for very helpful suggestions.
Funding
We are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for supporting this study. G.T.C. was supported by a CAPES scholarship. H.I.N. was supported by a FAPESP scholarship. B.S. is a recipient of a productivity scholarship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
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Cruvinel, G.T., Neves, H.I. & Spira, B. Glyphosate induces the synthesis of ppGpp. Mol Genet Genomics 294, 191–198 (2019). https://doi.org/10.1007/s00438-018-1499-1
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DOI: https://doi.org/10.1007/s00438-018-1499-1