Scientific Publications by FDA Staff

J Bacteriol 2009 Apr;191(8):2638-48

HtaA is an iron-regulated hemin binding protein involved in the utilization of heme-iron in Corynebacterium diphtheriae.

Allen CE, Schmitt MP

Many human pathogens including Corynebacterium diphtheriae, the causative agent of diphtheria, use host compounds such as heme and hemoglobin as essential iron sources. In this study, we examined the Corynebacterium hmu hemin transport region, a genetic cluster that includes a previously described ABC-type hemin transporter encoded by the hmuTUV genes and three additional genes, which we have designated htaA, htaB and htaC. The hmu gene cluster is composed of three distinct transcriptional units. The htaA gene appears to be part of an iron and DtxR-regulated operon that includes hmuTUV, while htaB and htaC are transcribed from unique DtxR-regulated promoters. Non-polar deletions of either htaA or the hmuTUV genes resulted in a reduced ability to use hemin as an iron source, while a deletion of htaB had no affect on hemin-iron utilization in C. diphtheriae. A comparison of the predicted amino acid sequence of HtaA and HtaB showed that they share some sequence similarity, and both proteins contain leader sequences and putative C-terminal trans-membrane regions. Protein localization studies with C. diphtheriae showed that HtaA is predominately associated with the cell envelope when grown in minimal medium, but is secreted during growth in nutrient rich broth. HtaB and HmuT were primarily detected in the cytoplasmic membrane fraction regardless of the growth medium. Hemin binding studies demonstrate that HtaA and HtaB are able to bind hemin, suggesting that these proteins may function as cell-surface hemin receptors in C. diphtheriae.