BhuR, a virulence-associated outer membrane protein of Bordetella avium, is required for the acquisition of iron from heme and hemoproteins

Infect Immun. 2002 Oct;70(10):5390-403. doi: 10.1128/IAI.70.10.5390-5403.2002.

Abstract

Iron (Fe) is an essential element for most organisms which must be obtained from the local environment. In the case of pathogenic bacteria, this fundamental element must be acquired from the fluids and tissues of the infected host. A variety of systems have evolved in bacteria for efficient acquisition of host-bound Fe. The gram-negative bacterium Bordetella avium, upon colonization of the avian upper respiratory tract, produces a disease in birds that has striking similarity to whooping cough, a disease caused by the obligate human pathogen Bordetella pertussis. We describe a B. avium Fe utilization locus comprised of bhuR and six accessory genes (rhuIR and bhuSTUV). Genetic manipulations of B. avium confirmed that bhuR, which encodes a putative outer membrane heme receptor, mediates efficient acquisition of Fe from hemin and hemoproteins (hemoglobin, myoglobin, and catalase). BhuR contains motifs which are common to bacterial heme receptors, including a consensus FRAP domain, an NPNL domain, and two TonB boxes. An N-terminal 32-amino-acid segment, putatively required for rhuIR-dependent regulated expression of bhuR, is present in BhuR but not in other bacterial heme receptors. Two forms of BhuR were observed in the outer membrane of B. avium: a 91-kDa polypeptide consistent in size with the predicted mature protein and a smaller 82-kDa polypeptide which lacks the 104 amino acids found at the N terminus of the 91-kDa form. A mutation in hemA was engineered in B. avium to demonstrate that the bacterium transports heme into the cytoplasm in a BhuR-dependent manner. The role of BhuR in virulence was established in turkey poults by use of a competitive-infection model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Bordetella / genetics
  • Bordetella / metabolism*
  • Bordetella / pathogenicity*
  • Bordetella Infections / etiology
  • Bordetella Infections / veterinary
  • Cloning, Molecular
  • DNA, Bacterial / genetics
  • Genes, Bacterial
  • Genetic Complementation Test
  • Heme / metabolism
  • Hemeproteins / metabolism
  • Hemin / metabolism
  • Humans
  • Iron / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Poultry Diseases / etiology
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Turkeys
  • Virulence / genetics
  • Virulence / physiology

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • BhuR protein, Bordetella pertussis
  • DNA, Bacterial
  • Hemeproteins
  • Receptors, Cell Surface
  • heme receptor
  • Heme
  • Hemin
  • Iron

Associated data

  • GENBANK/AY095952