ABC transporter FtsABCD of Streptococcus pyogenes mediates uptake of ferric ferrichrome

BACKGROUND: The Streptococcus pyogenes or Group A Streptococcus (GAS) genome encodes three ABC transporters, namely, FtsABCD, MtsABC, and HtsABC, which share homology with iron transporters. MtsABC and HtsABC are believed to take up ferric (Fe(3+)) and manganese ions and heme, respectively, while the specificity of FtsABCD is unknown. RESULTS: Recombinant FtsB, the lipoprotein component of FtsABCD, was found to bind Fe(3+ )ferrichrome in a 1:1 stoichiometry. To investigate whether FtsABCD transports Fe(3+ )ferrichrome, GAS isogenic strains defective in lipoprotein gene ftsB and permease gene ftsC were generated, and the effects of the mutations on uptake of Fe(3+ )ferrichrome were examined using radioactive (55)Fe(3+ )ferrichrome. FtsB was produced in the wild-type strain but not in the ftsB mutant, confirming the ftsB inactivation. While wild-type GAS took up 3.6 × 10(4 )Fe(3+ )ferrichrome molecules per bacterium per min at room temperature, the ftsB and ftsC mutants did not have a detectable rate of Fe(3+ )ferrichrome uptake. The inactivation of ftsB or ftsC also decreased (55)Fe(3+ )ferrichrome uptake by >90% under growth conditions in the case of limited uptake time. Complementation of the ftsB mutant with a plasmid carrying the ftsB gene restored FtsB production and (55)Fe(3+ )ferrichrome association at higher levels compared with the parent strain. The inactivation of mtsA and htsA and Fe-restricted conditions enhanced the production of FtsB and Fe(3+ )ferrichrome uptake. CONCLUSION: The FtsB protein bound Fe(3+ )ferrichrome, and inactivation of ftsB or ftsC, but not htsA or mtsA, diminished Fe(3+ )ferrichrome uptake, indicating that FtsABCD, but not HtsABC and MtsABC, is the transporter that takes up Fe(3+ )ferrichrome in GAS. Fe acquisition systems are virulence factors in many bacterial pathogens and are attractive vaccine candidates. The elucidation of the FtsABCD specificity advances the understanding of Fe acquisition processes in GAS and may help evaluating the GAS Fe acquisition systems as vaccine candidates.