J. Exp. Med., Volume 188, Number 6, September 21, 1998 1091-1103

Characterization of a Hemoglobin Protease Secreted by the Pathogenic Escherichia coli Strain EB1

By Ben R. Otto,^* Silvy J.M. van Dooren,^* Jan H. Nuijens, Joen Luirink,^* and Bauke Oudega^*

From the ^* Department of Molecular Microbiology, Institute of Molecular Biological Sciences, Biocentrum Amsterdam, 1081 HV Amsterdam, The Netherlands; and  Pharming BV, 2333 CA Leiden, The Netherlands

Many pathogenic bacteria can use heme compounds as a source of iron. Pathogenic Escherichia coli strains are capable of using hemoglobin as an iron source. However, the mechanism of heme acquisition from hemoglobin is not understood for this microorganism. We present the first molecular characterization of a hemoglobin protease (Hbp) from a human pathogenic E. coli strain. The enzyme also appeared to be a heme-binding protein. Affinity purification of this bifunctional protein enabled us to identify the extracellular gene product, and to clone and analyze its gene. A purification procedure developed for Hbp allowed us to perform functional studies. The protein interacted with hemoglobin, degraded it and subsequently bound the released heme. These results suggest that the protein is involved in heme acquisition by this human pathogen. Hbp belongs to the so-called IgA1 protease-like proteins, as indicated by the kinetics of its membrane transfer and DNA sequence similarity. The gene of this protein appears to be located on the large pColV-K30 episome, that only has been isolated from human and animal pathogens. All these characteristics indicate that Hbp may be an important virulence factor that may play a significant role in the pathogenesis of E. coli infections.

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