Scientific Publications by FDA Staff

J Bacteriol 2015 Feb 1;197(3):553-62

Utilization of host Iron Sources by Corynebacterium diphtheriae: Multiple Hemoglobin-Binding Proteins are Essential for the Use of Iron from the Hemoglobin/Haptoglobin Complex.

Allen CE, Schmitt MP

The use of hemin-iron by Corynebacterium diphtheriae requires the DtxR- and iron-regulated ABC hemin transporter HmuTUV and the secreted Hb-binding protein HtaA. We recently described two surface anchored proteins, ChtA and ChtC, which also bind hemin and Hb. ChtA and ChtC share structural similarities to HtaA; however, a function for ChtA and ChtC was not determined. In this study, we identified additional host iron sources that are utilized by C. diphtheriae. We show that several C. diphtheriae strains use the Hemoglobin-Haptoglobin (Hb-Hp) complex as an iron source. We report that an htaA deletion mutant of C. diphtheriae strain 1737 is unable to use the Hb-Hp complex as an iron source, and further demonstrate that a chtA-chtC double mutant is also unable to use Hb-Hp iron. Single deletion mutants of chtA or chtC use Hb-Hp iron in a manner similar to that of wild type. These findings suggest that both HtaA and either ChtA or ChtC are essential for the use of Hb-Hp iron. ELISA studies show that HtaA binds the Hb-Hp complex, and the substitution of a conserved tyrosine (Y361) for alanine in HtaA results in significantly reduced binding. C. diphtheriae was also able to use human serum albumin (HSA) and myoglobin (Mb) as iron sources, but not hemopexin. These studies identify a biological function for the ChtA and ChtC proteins and demonstrate that the use of the Hb-Hp complex as an iron source by C. diphtheriae requires multiple iron-regulated surface components.