Extracellular Heme Uptake and the Challenge of Bacterial Cell Membranes

Annu Rev Biochem. 2017 Jun 20:86:799-823. doi: 10.1146/annurev-biochem-060815-014214. Epub 2017 Apr 19.

Abstract

Iron is essential for the survival of most bacteria but presents a significant challenge given its limited bioavailability. Furthermore, the toxicity of iron combined with the need to maintain physiological iron levels within a narrow concentration range requires sophisticated systems to sense, regulate, and transport iron. Most bacteria have evolved mechanisms to chelate and transport ferric iron (Fe3+) via siderophore receptor systems, and pathogenic bacteria have further lowered this barrier by employing mechanisms to utilize the host's hemoproteins. Once internalized, heme is cleaved by both oxidative and nonoxidative mechanisms to release iron. Heme, itself a lipophilic and toxic molecule, presents a significant challenge for transport into the cell. As such, pathogenic bacteria have evolved sophisticated cell surface signaling and transport systems to obtain heme from the host. In this review, we summarize the structure and function of the heme-sensing and transport systems of pathogenic bacteria and the potential of these systems as antimicrobial targets.

Keywords: ABC transporter; TonB-dependent receptor; cell surface signaling; heme metabolism; heme transporter; membrane proteins.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biological Transport / drug effects
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cell Wall / drug effects
  • Cell Wall / metabolism
  • Gene Expression
  • Heme / antagonists & inhibitors*
  • Heme / metabolism
  • Iron / metabolism*
  • Metalloporphyrins / chemical synthesis
  • Metalloporphyrins / pharmacology
  • Models, Molecular
  • Protein Conformation
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / metabolism
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Siderophores / antagonists & inhibitors
  • Siderophores / biosynthesis
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Metalloporphyrins
  • Receptors, Cell Surface
  • Siderophores
  • heme receptor
  • Heme
  • Iron