A novel streptococcal integrative conjugative element involved in iron acquisition.
In this study, we determined the function of a novel non-ribosomal peptide synthetase (NRPS) system carried by a streptococcal integrative conjugative element (ICE), ICESe2. The NRPS shares similarity with the yersiniabactin system found in the high-pathogenicity island of Yersinia sp. and is the first of its kind to be identified in streptococci. We named the NRPS product 'equibactin' and genes of this locus eqbA-N. ICESe2, although absolutely conserved in Streptococcus equi, the causative agent of equine strangles, was absent from all strains of the closely related opportunistic pathogen Streptococcus zooepidemicus. Binding of EqbA, a DtxR-like regulator, to the eqbB promoter was increased in the presence of cations. Deletion of eqbA resulted in a small-colony phenotype. Further deletion of the irp2 homologue eqbE, or the genes eqbH, eqbI and eqbJ encoding a putative ABC transporter, or addition of the iron chelator nitrilotriacetate, reversed this phenotype, implicating iron toxicity. Quantification of (55)Fe accumulation and sensitivity to streptonigrin suggested that equibactin is secreted by S. equi and that the eqbH, eqbI and eqbJ genes are required for its associated iron import. In agreement with a structure-based model of equibactin synthesis, supplementation of chemically defined media with salicylate was required for equibactin production.
Heather
Zoe
Z
Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, UK.
Holden
Matthew T G
MT
Steward
Karen F
KF
Parkhill
Julian
J
Song
Lijiang
L
Challis
Gregory L
GL
Robinson
Carl
C
Davis-Poynter
Nicholas
N
Waller
Andrew S
AS
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D005810:Multigene Family; D010453:Peptide Synthases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012329:RNA, Bacterial / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D018502:Streptococcus equi / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013308:Streptonigrin / Q000494:pharmacology; D013379:Substrate Specificity
D001426:Bacterial Proteins; D002712:Chlorides; D005290:Ferric Compounds; D012329:RNA, Bacterial; D013308:Streptonigrin; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase; C024555:ferric chloride