Forward chemical genetic screens in Arabidopsis identify genes that influence sensitivity to the phytotoxic compound sulfamethoxazole

Pauline Fung,Jianfeng Zhang,David S Guttman,Yunchen Gong,Darrell Desveaux,Pauline W Wang,Ryan S Austin,Karl J Schreiber

doi:10.1186/1471-2229-12-226

Abstract

BackgroundThe sulfanilamide family comprises a clinically important group of antimicrobial compounds which also display bioactivity in plants. While there is evidence that sulfanilamides inhibit folate biosynthesis in both bacteria and plants, the complete network of plant responses to these compounds remains to be characterized. As such, we initiated two forward genetic screens in Arabidopsis in order to identify mutants that exhibit altered sensitivity to sulfanilamide compounds. These screens were based on the growth phenotype of seedlings germinated in the presence of the compound sulfamethoxazole (Smex).ResultsWe identified a mutant with reduced sensitivity to Smex, and subsequent mapping indicated that a gene encoding 5-oxoprolinase was responsible for this phenotype. A mutation causing enhanced sensitivity to Smex was mapped to a gene lacking any functional annotation.ConclusionsThe genes identified through our forward genetic screens represent novel mediators of Arabidopsis responses to sulfanilamides and suggest that these responses extend beyond the perturbation of folate biosynthesis.

Highlights

The sulfanilamide family comprises a clinically important group of antimicrobial compounds which display bioactivity in plants
We identified a mutant with reduced sensitivity to Smex, and subsequent mapping indicated that a gene encoding 5-oxoprolinase was responsible for this phenotype
The genes identified through our forward genetic screens represent novel mediators of Arabidopsis responses to sulfanilamides and suggest that these responses extend beyond the perturbation of folate biosynthesis

Summary

Introduction

The sulfanilamide family comprises a clinically important group of antimicrobial compounds which display bioactivity in plants. We initiated two forward genetic screens in Arabidopsis in order to identify mutants that exhibit altered sensitivity to sulfanilamide compounds. These screens were based on the growth phenotype of seedlings germinated in the presence of the compound sulfamethoxazole (Smex). Sulfanilamide compounds occupy a prominent place in history as the first synthetic molecules to be employed as antimicrobial chemotherapeutics in clinical and veterinary practice [1]. Since their discovery in the 1930s, thousands of sulfanilamide derivatives have been synthesized and their mechanism of action studied extensively. The influence of other metabolic pathways on sulfanilamide sensitivity is unknown

Methods

Results

Conclusion