Uptake of a catecholic cephalosporin by the iron transport system of Escherichia coli.
beta-Lactam antibiotics containing a catechol moiety show potent activity against Gram-negative bacteria, particularly organisms grown under iron-limited conditions, suggesting that the iron-regulated outer membrane proteins (IROMPs) play a role in antibiotic uptake. A catecholic C(7) alpha-formamido-substituted cephalosporin showed increased penetration into Escherichia coli cells grown in an iron-deficient medium compared with cells grown in a medium supplemented with iron. In contrast, penetration of the corresponding monohydroxyphenyl analogue was not influenced by iron concentration. Susceptibility studies with mutants of E. coli lacking one or more IROMPs suggested that the catecholic analogue was able to utilize the Fiu (83 kDa) and Cir (74 kDa) proteins, but not the enterobactin receptor FepA (81 kDa). Mutants lacking both Fiu and Cir showed a specific decreased susceptibility for catechol-containing cephalosporins. Radio-ligand binding studies with a Fe-catecholic cephalosporin confirmed an association with these proteins.
Critchley
I A
IA
SmithKline Beecham Pharmaceuticals, Chemotherapeutic Research Centre, Betchworth, Surrey, UK.
Basker
M J
MJ
Edmondson
R A
RA
Knott
S J
SJ
D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000378:metabolism; D001692:Biological Transport; D002511:Cephalosporins / Q000493:pharmacokinetics*; D003470:Culture Media; D004926:Escherichia coli / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D002511:Cephalosporins; D003470:Culture Media; C069878:BRL 41897A; D007501:Iron