Staphylococcus aureus elaborates two
citrate-containing
siderophores,
staphyloferrin A (SA) and
staphyloferrin B (SB), that enhance growth under
iron-restriction, yet, paradoxically, expression of the TCA cycle
citrate synthase, CitZ, is downregulated during
iron starvation.
Iron starvation does, however, result in expression of SbnG, recently identified as a novel
citrate synthase that is encoded from within the
iron-regulated SB biosynthetic locus, suggesting an important role for SbnG in staphyloferrin production. We demonstrate that during growth of S. aureus in
iron-restricted media containing
glucose, SB is produced but, in contrast, SA production is severely repressed; accordingly, SB-deficient mutants grow poorly in these media. Hypothesizing that reduced TCA cycle activity hinders SA production, we show that a citZ mutant is capable of SB synthesis, but not SA synthesis, providing evidence that SbnG does not generate
citrate for incorporation into SA. A citZ sbnG mutant synthesizes neither staphyloferrin, is severely compromised for growth in
iron-restricted media, and is significantly more impaired for virulence than either of the single-deletion mutants. We propose that SB is the more important of the two
siderophores for S. aureus insofar as it is synthesized, and supports
iron-restricted growth, without need of TCA cycle activity.