Susceptibility of Escherichia coli to the toxic L-proline analogue L-selenaproline is dependent on two L-cystine transport systems

Aims: L-Selenaproline (L-selenazolidine-4-carboxylic acid) is a toxic analogue of L-proline that inhibits the growth of the urinary tract pathogen Escherichia coli in both laboratory culture media and normal human urine. The aim of this study was to identify the transport systems involved in its uptake. Methods and Results: Deletion mutants from the Keio collection were tested for their susceptibility to L-selenaproline (SCA) and L-selenocystine (SeCys) on minimal salts agar medium. All single-gene mutants were sensitive to both compounds, but double mutants with deletions in fliY and ydjN or in yecS and ydjN were resistant to SCA and SeCys. The YdjN transporter active in strain JW1905 (ΔfliY::kan yecC⁺ yecS⁺ ydjN⁺) was inhibited by both SCA and SeCys, but the FliY YecS YecC ABC transporter system active in strain JW1718 (fliY⁺ yecC⁺ yecS⁺ ΔydjN::kan) was best inhibited by these compounds in the presence of dithiothreitol. Conclusions: L-selenaproline and L-selenocystine are accumulated by both the FliY YecC YecS and the YdjN L-cystine transporter systems in E. coli. Significance and Impact of the Study: Because susceptibility to selenium-containing analogues of L-proline and L-cystine is dependent on multiple transport systems, these compounds may be effective in the treatment of urinary tract infections.