Genomic adaptation of Burkholderia anthina to glyphosate uncovers a novel herbicide resistance mechanism

Glyphosate (GS) specifically inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase that converts phosphoenolpyruvate (PEP) and shikimate-3-phosphate to EPSP in the shikimate pathway of bacteria and other organisms. The inhibition of the EPSP synthase depletes the cell of the EPSP-derived aromatic amino acids as well as of folate and quinones. A variety of mechanisms (e.g., EPSP synthase modification) has been described that confer GS resistance to bacteria. Here, we show that the Burkholderia anthina strain DSM 16086 quickly evolves GS resistance by the acquisition of mutations in the ppsR gene. ppsR codes for the pyruvate/ortho-P-i dikinase PpsR that physically interacts and regulates the activity of the PEP synthetase PpsA. The mutational inactivation of ppsR causes an increase in the cellular PEP concentration, thereby abolishing the inhibition of the EPSP synthase by GS that competes with PEP for binding to the enzyme. Since the overexpression of the Escherichia coli ppsA gene in Bacillus subtilis and E. coli did not increase GS resistance in these organisms, the mutational inactivation of the ppsR gene resulting in PpsA overactivity is a GS resistance mechanism that is probably unique to B. anthina.

Automated summary

Glyphosate inhibits EPSP synthase in bacteria and other organisms, causing depletion of aromatic amino acids, folate, and quinones. The Burkholderia anthina DSM 16086 strain develops resistance to glyphosate by acquiring mutations in the ppsR gene, resulting in increased cellular PEP concentration that prevents EPSP synthase inhibition. Overexpression of the E. coli ppsA gene did not confer glyphosate resistance in B. subtilis and E. coli, suggesting that the mutational inactivation of ppsR leading to PpsA overactivity is a unique mechanism in B. anthina.