Iron acquisition from heme and hemoglobin by a Serratia marcescens extracellular protein.

Abstract

Several pathogenic bacteria are able to use heme and hemoproteins as iron sources independent of siderophore production by mechanisms involving outer membrane heme-binding proteins and heme transport systems. Here we show that Serratia marcescens has such a property and we identify an extracellular heme-binding protein, HasA (for heme acquisition system), allowing the release of heme from hemoglobin. This protein is secreted by S. marcescens under conditions of iron depletion and is essential for heme acquisition.

Deciphering the Structural Role of Histidine 83 for Heme Binding in Hemophore HasA

“…Preparation of HasA Proteins-Wild-type hemophore HasA WT from S. marcescens, and mutant H83A were obtained and cloned as previously reported (2,20). Uniformly 15 N-and 15 N/ 13 C-labeled proteins were produced at 303 K in M9 minimal medium containing 15 NH 4 Cl and 13 C-glycerol as the sole nitrogen and carbon sources and were purified as described previously (9,21).…”

“…The first hemophore was discovered in Serratia marcescens (2). Since then, several orthologs have been found in Pseudomonas aeruginosa (3), Pseudomonas fluorescens (4), Yersinia pestis (5), Yersinia enterocolytica (Sanger Institute) and Yersinia pseudotuberculosis (6).…”

The Crystal Structure of the Secreted Dimeric Form of the Hemophore HasA Reveals a Domain Swapping with an Exchanged Heme Ligand

“…The hemophore secreted by the opportunistic pathogen Serratia marcescens, HasA, was the first to be identified (1) and is now very well characterized. It is secreted under iron deficiency condition by an ABC-type pathway via a C-terminal secretion signal.…”

Functional Differences between Heme Permeases: Serratia marcescens HemTUV Permease Exhibits a Narrower Substrate Specificity (Restricted to Heme) Than the Escherichia coli DppABCDF Peptide-Heme Permease

“…A more elaborate heme uptake system is present in fewer species, such as Serratia marcescens and Pseudomonas and Yersinia species. This system involves bacterial extracellular proteins called hemophores (10). Because of their high affinity for heme, hemophores extract this compound from various host hemoproteins and convey it to hemophorespecific outer membrane receptors (HasR) that internalize only heme (27).…”