Use of Heme Compounds as Iron Sources by Pathogenic Neisseriae Requires the Product of the hemO Gene

Abstract

Heme compounds are an important source of iron for neisseriae. We have identified a neisserial gene, hemO, that is essential for heme, hemoglobin (Hb), and haptoglobin-Hb utilization. The hemO gene is located 178 bp upstream of the hmbR Hb receptor gene in Neisseria meningitidis isolates. The product of the hemO gene is homologous to enzymes that degrade heme; 21% of its amino acid residues are identical, and 44% are similar, to those of the human heme oxygenase-1. DNA sequences homologous to hemO were ubiquitous in commensal and pathogenic neisseriae. HemO genetic knockout strains of Neisseria gonorrhoeae and N. meningitidis were unable to use any heme source, while the assimilation of transferrin-iron and iron-citrate complexes was

The Heme Oxygenase(s)-Phytochrome System of Pseudomonas aeruginosa

“…Heme labeled with 13 C was obtained utilizing previously reported methodology (9, 20 -22) developed to take advantage of the fact that the first committed precursor in heme biosynthesis is ALA (23). Thus, 13 C-labeled heme, which was biosynthesized in Escherichia coli upon addition of suitably labeled ALA, was trapped by simultaneously expressing rat liver outer mitochondrial membrane cytochrome b 5 . The details of the biosynthetic protocol, which entail the expression and purification of outer mitochondrial membrane cytochrome b 5 harboring 13 C-labeled heme, have been presented previously (9, 20 -22).…”

Crystal Structures of the NO- and CO-bound Heme Oxygenase from Neisseriae meningitidis

“…HO also is present in some pathogenic bacteria such as Corynebacterium diphtheriae, Neisseriae meningitidis, and Pseudomonas aeruginosa (11)(12)(13)(14)(15). In bacteria, heme oxygenase is a soluble cytoplasmic protein, which takes part in the mining of iron from host heme.…”

“…These bacteria express highly specific outer membrane receptors that bind different heme-containing compounds, extract heme from these compounds, and then transport heme into the bacterial cytoplasm (17,18). In the Gram-negative bacterium N. meningitidis, a heme oxygenase (nm-HO) also is necessary for use of iron from imported heme and appears to be transcriptionally linked with an outer membrane heme receptor (11). Besides being essential in iron assimilation, nm-HO protects N. meningitidis from heme toxicity by degradation of heme (12).…”

Solution 1H NMR Investigation of the Active Site Molecular and Electronic Structures of Substrate-bound, Cyanide-inhibited HmuO, a Bacterial Heme Oxygenase fromCorynebacterium diphtheriae

“…In higher plants, algae, and cyanobacteria, HO generates the open tetrapyrroles as lightharvesting pigments (8). HO has also been identified in several pathogenic bacteria, where its role appears to be the essential "mining" of iron from hemes in the host (9,10). Plant and bacterial HOs are soluble and somewhat shorter (ϳ200 residues) (9, 10) than mammalian HO (11).…”

“…Plant and bacterial HOs are soluble and somewhat shorter (ϳ200 residues) (9, 10) than mammalian HO (11). Among the characterized bacterial HOs, sequence homology to the more extensively studied mammalian HO varies from relative high (33% sequence identity/70% similarity) for HmuO from Corynebacterium diphtheriae (10) to low (Ͻ25%) for HemO from Neisseria meningitides (9).…”