title: Susceptibility of Escherichia coli to the toxic L-proline analogue L-selenaproline is dependent on two L-cystine transport systems.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Mathematical and Natural Sciences, Arizona State University at the West Campus, Phoenix, AZ, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Deutch
authors.forename: I
authors.initials: I
authors.lastname: Spahija
authors.forename: C E
authors.initials: CE
authors.lastname: Wagner
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D003470:Culture Media; D003553:Cystine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D016566:Organoselenium Compounds / Q000633:toxicity*; D011392:Proline / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D000900:Anti-Bacterial Agents; D003470:Culture Media; D029968:Escherichia coli Proteins; D016566:Organoselenium Compounds; C000604954:YdjN protein, E coli; C009226:selenocystine; D003553:Cystine; C014811:selenaproline; D011392:Proline
keywords: Escherichia coli; L-cystine transport; L-selenaproline; L-selenazolidine-4-carboxylic acid; L-selenocystine; proline analogue; urinary tract infection