ABSTRACT
Yersinia pestis possesses a heme-protein acquisition system (Hmu) that allows it to utilize heme and heme-protein complexes as the sole sources of iron. Analysis of the Y. pestisCO92 genomic sequence revealed a second heme-protein acquisition gene cluster that shares homology with the hemophore-dependent heme acquisition system (Has system) of Serratia marcescens. This locus consisted of thehasR
yp
receptor gene, thehasA
yp
hemophore gene, and genes encoding components of the HasAyp dedicated ABC transporter factor (hasDE
yp
), as well as atonB homologue (hasB
yp). By using a reconstituted secretion system in Escherichia coli, we showed that HasAyp is a secreted heme-binding protein and that expression of HasAyp is iron regulated in E. coli. The use of a transcriptional reporter fusion showed that the hasRADEB promoter is Fur regulated and has increased activity at 37°C. Hemoglobin utilization via the Hasyp system was studied with both E. coli and Y. pestis, for which hasand has hmu mutant strains were used. No contribution of the Has system to heme utilization was observed in either E. coli or Y. pestis under the conditions we tested. Previously it was shown that a deletion of the Hmu system had no effect on the virulence of Y. pestis in a mouse model of bubonic plague. An Hmu− Has− double mutant also retained full virulence in this model of infection. This report constitutes the first attempt to investigate the contribution of the hemophore-dependent heme acquisition system in bacterial pathogenicity.
Direct Hemin Transfer from IsdA to IsdC in the Iron-regulated Surface Determinant (Isd) Heme Acquisition System ofStaphylococcus aureus